Ongoing Projects

PATH CVIA 108 PROJECT:

Infant Malaria Vaccine Schedule Optimization

Study Period: May 2024- December 2027

The CVIA 108 project is a Phase 2b multicenter randomized, placebo-controlled, double-blind, study evaluating the safety, immunogenicity and efficacy of R21/Matrix-M Malaria Vaccine (R21/MM)  in African infants with different immunization schedules. The project is implementated by Infectious Diseases Research Collaboration (IDRC) with funding from PATH Center for Vaccine Innovation and Access (Grant number: IDRC- Uganda_GAT.588511-01728256-PRE).

R21/MM vaccine has been recommended by the World Health Organisation to prevent clinical malaria in young children living in moderate to high transmission areas of Sub-Saharan Africa; with the first dose delivered at 5-6 months of age and two subsequent doses given monthly. The vaccine has not been evaluated for efficacy in younger groups. Thus, evidence about the safety, immunogenicity, and efficacy of R21/MM in younger infants is lacking.

The project will evaluate how age at first paediatric vaccine dose and time intervals between doses modify the immunogenicity of the vaccine and the efficacy in protecting infants against Plasmodium falciparum malaria clinical disease. We will compare the safety, immunogenicity, and efficacy of three doses of R21/MM in infants at 6 weeks of age at time of first vaccination in a conventional 6-10-14 week vaccine schedule (compressed schedule) and in infants at 8 weeks of age at time of first vaccination receiving three doses at 8-16-24 weeks (relaxed schedule). All infants will receive their routine paediatric vaccines on the same visits. Placebo arms will be included to evaluate both efficacy and potential interference of immune responses from co-administered routine vaccine.

Objectives

Primary objectives

1. Immunogenicity: To describe the anti-CS NANP antibody responses elicited following the primary 3-dose schedule of R21/MM for the “compressed” as compared to the “relaxed” immunization schedule categories.
2. Safety: To describe the reactogenicity, tolerability, and safety of R21/MM administered as a four-dose regimen to vaccine-naïve infants in two different vaccine immunization schedule categories (“compressed” and “relaxed”), with a booster dose (dose 4) at 15 months of age, when co-administered with routine immunizations

Secondary objectives

1. Immunogenicity: To describe the anti-CS NANP antibody responses elicited following the 4th dose of R21/MM for the “compressed” as compared to the “relaxed” immunization schedule categories.
2. Efficacy:
3. To evaluate the protective efficacy of R21/MM against clinical malaria disease caused by Plasmodium falciparum (Pf) by assessing time-to-first malaria episode in African infants randomized to either the “compressed” or “relaxed” immunization schedule category.
4. To evaluate the protective efficacy of R21/MM against all episodes of clinical malaria disease caused by Plasmodium falciparum by assessing the number of clinical malaria episodes in African infants randomized to either the “compressed” or “relaxed” immunization schedule category

Study Site:  IDRC Tororo study clinic

Principal Investigator: Dr. Joaniter I. Nankabirwa

Study Sponsor: PATH Center for Vaccine Innovation and Access

MMS in Ugandan refugees project

Surveillance of P. falciparum Drug and Diagnostic Resistance in Refugee Populations

Study Period: May 2024-April 2027

The malaria molecular surveillance (MMS) in Ugandan refugee populatons is a three-year project funded by the BMGF (Grant ID: INV-067853) and GSK (Grant number 222739) to conduct a comprehensive malaria molecular surveillance in refugee populations and generate high quality molecular, epidemiological and entomologic data for monitoring the geographic and temporal trends in key malaria genomic and epidemiologic data to inform interventions to best protect refugee and local host populations. This project is led by the Infectious Diseases Research Collaboration (IDRC) in collaboration with the University of California, San Francisco (UCSF), Makerere University, Kampala, Uganda, Uganda Christaian University, Mukono, Uganda,  the Ministry of Health Uganda (MoH), Brown University, USA, Malaria Consortium, South Sudan, and National Institute of Public Health, Burundi

 Malaria remains a major global health problem, and emerging antimalarial drug and diagnostic resistance in Africa threaten control efforts. Investments in molecular, parasitological, and clinical surveillance have enabled the early detection of emerging resistance phenotypes, facilitating informed policy changes before resistance becomes widespread. However, conflicts and instability make routine surveillance nearly impossible in large areas of the continent, leaving significant gaps in our understanding of the dynamics of emerging resistance. Performing safe and effective molecular surveillance in parasite populations originating from conflict zones will be important to characterize malaria epidemiology, enabling mitigation of the impacts of resistance.

Objectives

• To characterize drug resistance profiles of falciparum parasites collected from newly arrived refugees, local host populations, and populations living in conflict regions.
• To characterize diagnostic resistance in falciparum parasites collected from newly arrived refugee, local host populations, and populations living in conflict regions.
• To support cross-border collaboration to improve regional surveillance for drug and diagnostic resistance.

Study Site:  Uganda, Burundi, Democratic Republic of Congo and South Sudan, and other countries from where the refugees are originating.

Collaborators: Infectious Diseases Research Collaboration (IDRC), Uganda Ministry of Health (MoH), Makerere University, University of California, San Francisco (UCSF), Uganda Christaian University, Brown University, Malaria Consortium, South Sudan, and National Institute of Public Health, Burundi

Principal Investigator: Stephen Tukwasibwe

Study Sponsor: BMGF and GSK

Title: Mechanisms of varied sensitivity of P. falciparum field isolates to the antimalarial drug pipeline (VSPA)

Study period:  2023 – 2028

Major Goals: 

1. To characterise ex vivo sensitivity to lead antimalarial compounds of P. falciparum field isolates. 

2. To characterise genotypes of drug sensitivity outliers to identify mediators of decreased sensitivity in field isolates to lead antimalarial compounds. 

3. To characterise phenotypes of drug sensitivity outliers to elucidate resistance mechanisms of lead antimalarial compounds.

Study site: Tolab, Laboratory Tororo, Kalongo Laboratory and Molab and Butabika Kampala Laboratories

Collaborators: Infectious Diseases Research Collaboration (IDRC), Makerere University College of Health Sciences, University of California San Francisco, Stanford University
Principal Investigators: Samuel L. Nsobya Mellissa Conard, Roland Cooper and  Philip Rosenthal  
Study Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)

Title: Resistance of Malaria Parasites to Artemisinin-Based Therapies (REACT)

Study period: 2020 – 2025

Major Goals: The goals of this project are: 

(1) To assess impacts of selective pressures for resistance of malaria parasites to ACTs used for the treatment and chemoprevention of malaria,

(2) To characterize phenotypes associated with diminished drug sensitivity, and (3) to identify mediators of high level drug resistance.

Study site: Tolab, Laboratory Tororo, Kalongo Laboratory and Molab and Butabika Kampala Laboratories

Collaborators: Infectious Diseases Research Collaboration (IDRC), Makerere University College of Health Sciences, University of California San Francisco, Stanford University
Principal Investigators: Samuel L. Nsobya Mellissa Conard,  Roland Cooper and Philip Rosenthal  
Study Sponsor: National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID)

Surveillance to track and characterise antimalarial resistance trends in Ugandan Plasmodium falciparum parasites (STARTUP) 

Study period: 2022-2027.

Major Goals: 

We will characterise emerging antimalarial resistance at field sites across Uganda. We will use molecular, parasitological and epidemiological approaches to understand better the extent and origins of drug resistance, the genotypes that contribute to resistance, and the epidemiological factors that facilitate the evolution of resistant parasites. We hypothesise that multiple locally derived artemisinin-resistant lineages have emerged but that only a subset of lineages with optimal fitness will expand geographically; that decreased efficacy of artemisinins will facilitate the selection of resistance to key partner drugs; and that certain ecological and epidemiological factors will be associated with the geographical and temporal spread of resistant parasites. We will test these hypotheses with the following aims.

Aim 1. Molecular characterisation of resistance to artemisinins and key partner drugs in Uganda

Aim 2. Parasitological characterisation of resistance to artemisinins and key partner drugs in Uganda

Aim 3. Characterisation of ecological and epidemiological factors associated with ACT resistance markers.

Study site: Tolab, Laboratory Tororo, Kalongo Laboratory and Molab and Butabika Kampala Laboratories

Collaborators: Infectious Diseases Research Collaboration (IDRC), University of California San Francisco, Stanford University, Makerere University College of Health Sciences
Principal Investigators: Samuel L. Nsobya Mellissa Conard, Philip Rosenthal and Roland Cooper 
Study Sponsor: National Institutes of Health (NIH)

UGANDA LEARNING HUB FOR IMMUNISATION EQUITY

Study Period: February 2023 – December 2025

With support from Gavi, the Vaccine Alliance, the Infectious Diseases Research Collaboration (IDRC) together with PATH and Makerere University School of Public Health (MakSPH) are implementing a three-year Learning Hub (LH) for immunization equity project in Uganda. The LH is being implemented in close collaboration with the immunisation program of the Ministry of Health and aims to generate evidence on identifying and reaching Zero Dose children (ZDC), Under Immunized (UI) children, and missed communities in Uganda to inform immunization equity interventions. Specifically, the project seeks to:

1. characterize the ZDC, UI children, and missed communities in Uganda, and understand the barriers and challenges of reaching them.
2. examine the implementation outcomes (i.e., acceptability, reach, adoption, fidelity, implementation cost, sustainability and effectiveness) of ongoing and planned immunisation approaches to reaching ZDC, UI children, and missed communities in Uganda.
3. evaluate the utility of different data capture platforms for identifying ZDC, UI, and missed communities in Uganda.

Principal investigator/Hub director: Prof. Moses Kamya
Study Site: Kasese, Mubende and Wakiso districts

Achievements
• A launch meeting for the project was held on 27th March 2024.
• Developed a learning agenda to inform the design and implementation of the immunization equity interventions in Uganda.
• Conducted a rapid assessment of barriers to reaching ZDC and UI children between August 2023 and March 2024 in Kasese, Wakiso and Mubende districts.
• Undertook an evaluation of the utility of the different data capture platforms for identifying ZDC, UI and missed communities in Uganda in Lira and Mukono districts (March to December 2023).
• Conducted an evaluation of UNICEF’s zero dose support to Kamuli and Wakiso districts (November 2023 to July 2024).
• Conducted a baseline targeted community survey in Mubende district in April to June 2024.
• Conducted dissemination meetings in Mubende (on 21st June 2024) and at national level (on 28th June 2024)

The immune response to malaria within the germinal centre (Tonsil Studies) 

Study period: November 2022-October 2023

This project aims to study the development of adaptive immunity to malaria in the germinal centre using tonsil tissues obtained from children living in malaria-endemic areas who have undergone tonsillectomy at Mbale Regional Referral Hospital. Specifically, the study aims to:

1. Map the immune response within the tonsil during malaria infection, 
2. Use tonsil cells from malaria infection and/or previously exposed children in germinal centre organoids to study malaria immune responses in vitro.

Study site: Mbale Regional Referral Hospital

Collaborators: Infectious Diseases Research Collaboration, Busitema University, Queensland Institute of Medical Research (QIMR) Berghofer, Burnet Institute (Australia) and Stanford University

Principal Investigators: Abel Kakuru, Michelle Boyle, and Christine Adoch,

Study Sponsor: Queensland Institute of Medical Research (QIMR) Berghofer

P4P STUDY PROFILE:
Title: Community-based, peer-delivered PrEP for women engaged in sex work in rural Uganda: The Peers for PrEP (P4P) study.
Study period: (2022-2026)
Study synopsis: This study is being conducted in Ntungamo district in Southwestern Uganda in two communities (Rubaare and Rwashamaire). The study comprises two phases: Phase A – intervention development and refinement – followed by Phase B – a single arm pilot trial to evaluate the hypothesis that a community-based, peer-delivered PrEP intervention for women engaged in sex work (WESW) in rural southwestern Uganda will be feasible, acceptable, and increase PrEP uptake and adherence vs. standard of care (SOC).

Objectives:
Phase A Primary Objective: To develop and refine a community-based, peer-delivered PrEP intervention for women engaged in sex work in rural Uganda
Phase B Primary Objective: To assess the feasibility, acceptability, and preliminary effectiveness of a community-based, peer-delivered PrEP intervention for women engaged in sex work in rural Uganda
Study site: Ntungamo district in rural Southwestern Uganda.
Collaborators: Infectious Diseases Research Collaboration (IDRC), Makerere University College of Health Sciences, University of California San Francisco, Stanford University.

Principle investigators: Catherine A. Koss, Jane Kabami.
Co-investigators: Moses R. Kamya, Laura B. Balzer, Cecilia Akatukwasa, Jennifer Velloza & James Rooney.
Study sponsor: University of California, San Francisco (UCSF).
Study funder: Gilead Sciences.

IMMRSE-U: Implementing Malaria MoleculaR SurveillancE in Uganda

Study Period: November 2021-November 2024

This project is a collaboration between IDRC, the Uganda Ministry of Health, the NIH-funded African Center of Excellence in Bioinformatics (ACE), and the University of California, San Francisco, to integrate malaria genomics data into routine surveillance activities in Uganda. 

Objectives

• Estimate prevalence and spread of drug and diagnostic malaria parasites in Uganda

• Estimate prevalence of non-falciparum malaria infections across Uganda

• Estimate trends in malaria epidemiology and transmission using data from health centres

• Regularly disseminate genomic data to the Uganda Ministry of Health (NMCD) to inform malaria control policy

This study will collect Dry Blood Spot (DBS) samples for malaria genomic analysis from at least 30 health centres across Uganda in areas of varying malaria transmission. Of particular importance are areas of low transmission targeted for malaria elimination, border districts, and areas earmarked for drug and diagnostic resistance surveillance. 

Highly multiplex amplicon deep sequencing performed on these samples will provide genomic data that can be linked to individual-level malaria surveillance data from the health facilities. By collecting genomic information twice yearly at locations across the country, this study will allow for increased monitoring for HRP2/3 deletions and drug resistance mutations and to monitor their spread. 

It also involves the training and mentoring of five bioinformatics scientists and establishing a state-of-the-art genomics facility at the Central Public Health Laboratory in Butabika, Uganda. 

This study will generate actionable, impactful information for the Ministry of Health and National Malaria Control Division.  

Study Site: Butabika Hospital

Collaborators: Infectious Diseases Research Collaboration (IDRC), Uganda Ministry of Health (MoH), NIH-funded African Center of Excellence in Bioinformatics (ACE), and the University of California, San Francisco

Principal Investigators–Uganda: Dr Isaac Ssewanyana, Prof. Moses Kamya, Prof. Sam Nsobya (Makerere University and IDRC). 

Principal Investigators-USA: Dr. Jessica Briggs, Dr. Melissa Conrad, Dr. Bryan Greenhouse and Dr. Phil Rosenthal (UCSF)

Study Sponsor: The Bill & Melinda Gates Foundation 

Project : Feasibility of Primary Repair for Anorectal Malformations in Uganda

Study period 2021-2022

Background Surgically correctable congenital anomalies account for an increasing burden of death and disability for children in low- and middle-income countries (LMIC).

In our setting, most patients with ARMs undergo three separate staged operations: 1) initial colostomy formation; 2) repair of the ARM (called anoplasty), and 3) colostomy closure. Three operations result in a long treatment duration, potential complications with each procedure, delays in care, and stigma associated with ostomies. We have previously demonstrated that children live 2-3 years on average with their ostomies, and that over a third of families experience catastrophic health expenditure. Half of male caregivers leave the family and children are not allowed to attend school with an ostomy. An intervention that shortens duration of life with an ostomy would reduce the financial burden, social rejection, and school attendance. In higher-income countries, some children receive a single operation or a 2-stage procedure. Safety of a 1- or 2-stage procedure in Uganda is unknown, due to the different resources available, and associated social and economic impact for families is also unknown.  My specific aims are designed to address these important gaps in knowledge.

Significance

By offering 1- or 2- stage procedures for ARMs in a resource-limited setting, we expect to reduce health care expenditure by families, length of treatment, length of hospital stay, frequency of hospital visits, and social rejection. The results could also have a broad impact on improving the standard of pediatric surgical care in LMICs like Uganda by demonstrating that a single stage repair is feasible in a resource-limited setting, and offering guidelines such as the ARM score that may be used in similar settings.

Objectives

1: To determine the effectiveness and complications of 1- and 2- stage repair for ARMs.

2: To develop an ARM score to guide decision-making for need of staged procedures with an ostomy, rather than primary anoplasty.

3: To assess the financial and social impact of reducing or eliminating time living with an ostomy for children with ARMs.

Study site: Mbarara Regional Referral/Teaching  hospital

Mentors Professor Doruk. Ozgediz and Dr. Olivia Kituuka, Dr. Martin Situma, and Dr. Francis Bajunirwe

Principal Investigator Felix Oyania

Study sponsor The National Institute of Diabetes and Digestive and Kidney Diseases and the Fogarty International Center of the National Institutes of Health (NIH) under Award Number D43TW009343 and the University of California Global Health Institute (UCGHI).

Portfolio approach to developing the next generation of malaria treatments for Africa (“PAMAFRICA”)

Study Period: April 2020-March 2025

The PAMAfrica consortium brings together a global medicines company, a not-for-profit product development partnership and leading academic institutions in Africa and Europe. PAMAfrica aims to develop new medicines for severe and uncomplicated malaria to combat emerging artemisinin resistance. The projects include developing the first new malaria treatment for babies under 5kg, a new fast-acting medicine for severe malaria, and new combinations to treat drug-resistant uncomplicated malaria.

The European & Developing Countries Clinical Trials Partnership (EDCTP) awarded a new grant to the new PAMAfrica research consortium led by Medicines for Malaria Venture (MMV). The consortium will support the development of new treatments for malaria in the most at-risk populations, including babies, patients with severe malaria, and those with drug-resistant infections. The EDCTP grant of €21.9 million will be matched by funding from MMV, Novartis and partners. Over 5 years, the grant will support the development of a portfolio of projects executed under the umbrella of the PAMAfrica research consortium. Clinical trial capabilities in Africa will also be strengthened to ensure each site involved can effectively operate to ICH-GCP regulatory standards. The consortium includes seven research organisations from Burkina Faso, Gabon, Germany, Mozambique, Spain and Uganda, and Novartis and Merck pharmaceutical companies. IDRC will conduct two clinical trials and support efforts to build clinical capacity and train scientists across Africa.

1. An adaptive, randomized, active-controlled, open-label, sequential cohort, multicentre study to evaluate the efficacy, safety, tolerability and pharmacokinetics of intravenous cipargamin (KAE609) in adult and paediatric participants with severe Plasmodium falciparum malaria (KARISMA – KAE609’s Role in Severe Malaria)

The study will evaluate the efficacy, safety, tolerability and pharmacokinetics (PK) of intravenous cipargamin in participants with severe Plasmodium falciparum malaria. Severe malaria is a medical emergency and is affecting primarily young children in Africa. Injectable artesunate is the standard of care for treating severe malaria and is highly efficacious. However, the spread of artemisinin resistance in Plasmodium falciparum in Asian countries poses a threat for future treatment of patients with this life-threatening disease. To mitigate this risk, there is a need for another drug in malaria-endemic countries. Cipargamin treatment results in rapid clearance of parasites, including artemisinin-resistant parasites. This study investigates the efficacy (parasite reduction and clinical outcome), safety, tolerability and pharmacokinetics of different injectable dose regimens of cipargamin compared to injectable artesunate. 

This will be an adaptive, multicentre, randomised, open-label, sequential cohort study in participants aged ≥ 12 years (Cohorts 1-2) and ≥ 6 months to < 12 years (Cohorts 3-5) with a diagnosis of moderately severe and severe P. falciparum malaria. The first cohort (Cohort 1) will be small, including participants aged 12 years or over-diagnosed with moderately severe malaria and high parasitemia. This cohort will evaluate safety and parasite clearance rates before continuing into Cohorts 2-5, including only severe malaria patients according to WHO criteria. Progressively younger participants will be included with each new cohort from Cohort 2 onwards. This design aims at minimising risks for paediatric participants < 12 years.

Participants will be hospitalised under close supervision for at least 72 hours after initiating IV treatment and until oral treatment with Coartem has been undertaken. Hospitalisation can be extended for participants based on disease signs until IV treatment has been completed and oral treatment with Coartem has been initiated. All participants will be followed up until Day 29. The sponsor will continuously monitor data related to participants’ efficacy and safety. If participants randomised to any IV cipargamin arms meet either the safety criteria or lack of efficacy criteria, the study may be paused and a data safety review conducted.

2. Phase IIa Proof of Concept, Multicentre, Randomized, Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of the Combination M5717 plus Pyronaridine Administered once Daily for 1 or 2 Days to Adults and Adolescents with Acute Uncomplicated Plasmodium falciparum Malaria

Artemisinin-based combination therapies (ACTs) have been the gold standard for acute uncomplicated P. falciparum malaria. Still, the increasing reports of emergent resistant strains to artemisinin-related compound therapies make looking for new therapeutic tools necessary. In this context, the current study intends to explore in a Proof of Concept the safety, preliminary efficacy, and pharmacokinetics (PK) of M5717 (free base) in combination with pyronaridine (tetraphosphate). An ACT containing a variety of pyronaridine-artesunate (Pyramax) will be used as internal control, mainly for safety.

The study is a Phase IIa, randomised, open-label, multicentre study in adults and adolescents (≥ 12 and ≤ 55) diagnosed with acute uncomplicated P. falciparum malaria. The study will consist of 2 parts. Part A will be a small safety/PK run-in group of 12 adults with acute uncomplicated P. falciparum malaria designed to monitor safety and exposure. After the Internal Data Monitoring Committee (IDMC) reviews safety stopping criteria assessment, Part B will continue at the planned or adjusted dose based on exposure in Part A. Part B will include adults and adolescents (≥ 12 and ≤ 55 years of age). A cohort B0 composed of 25 adults and adolescents will serve as the basis to ensure the 1-day dosing leads to the expected exposures. After the IDMC decision on Cohort B0 safety, efficacy, and PK, 25, 50, and 25 participants will be randomised to Cohorts B1, B2, and B3. The intent is to develop a 1- or 2-day dosing regimen of the M5717-pyronaridine combination.

PAMAfrica Master’s in Biostatistics Program

The European & Developing Countries Clinical Trials Partnership (EDCTP) awarded a grant to the new PAMAfrica research consortium led by Medicines for Malaria Venture (MMV). The consortium includes seven research organisations from Burkina Faso, Gabon, Germany, Mozambique, Spain and Uganda and a pharmaceutical company, Novartis. The grant will support efforts to build and strengthen human clinical research capacity through scholarships for a Master’s degree in Biostatistics. Two students from Uganda will be supported for the Master’ degree in Biostatistics training. The MSc Biostatics degree programme focuses on quantitative research in health-related fields to develop a career in Biostatistics, a growing field in sub-Saharan Africa due to increased biomedical research. The support aims to enhance Bio statistical graduate training capacity and boost the number of researchers and practitioners. 

PAMAfrica PhD programme

PAMAfrica grant includes 5 PhD scholarships for students coming from the following partnering institutions (1 scholarship per institution):

• CISM/Fundacao Manhica, Mozambique

• CERMEL, Gabon

• Groupe de Recherche Action en Sante (GRAS), Burkina Faso

• Infectious Diseases Research Collaboration (IDRC), Uganda

• Centre National de la Recherche Scientifique et Technologique (CNRST) – Institute de Recherche en Science de la Santé (IRSS), Burkina Faso

The Institute for Tropical Medicine (ITM), University of Tübingen, hosts the PhD program. Institute for Tropical Medicine (ITM) is a leading institution performing clinical trials in infectious diseases, especially antimalarial interventions and vaccines, at its dedicated Clinical Trials Platform (CTP) and in collaboration with partner sites in tropical countries. 

Study Site: Tororo Hospital, Tororo District

Collaborators: Medicines for Malaria Venture (MMV)

Principal Investigators: Dr Yeka Adoke

Study Sponsor: EDCTP

Case Managers and Peer Support Groups (CAMPS) for Prophylaxis Adherence in Rheumatic Heart Disease

Study Period: August 2022- July 2023

The CAMPS study is a pragmatic randomised field trial to test and evaluate scalable secondary antibiotic adherence support models for children newly diagnosed with rheumatic heart disease (RHD), integrated within routine care at the health centre IIIs and IVs over 12 months.

RHD is the most common acquired cardiovascular disease among children and young adults, with at least 40.5 million current clinical cases worldwide. RHD is responsible for 340,000 annual deaths and accounts for the most significant cardiovascular disease-related loss of disability-adjusted life years among 10-14-year-olds. Studies suggest that early diagnosis and initiation of secondary antibiotic prophylaxis (SAP) improves 2-year outcomes for children with latent RHD. However, long courses of SAP with every-4-week BPG are very challenging to maintain worldwide. 

CAMPS aim to determine 1-year BPG adherence rates of children newly diagnosed with latent RHD in Uganda randomised to one of two support strategies: a) Usual care (Arm 1) and b) Peer group + Case Manager strategy (Arm 2). The primary outcome will be adherence to secondary antibiotic prophylaxis at 12 months. CAMPS will also explore patient-reported outcomes, including treatment satisfaction, patient health-related quality of life, and caregiver quality of life, in relation to support strategy.

The CAMPS study runs in the Tororo district in Eastern Uganda at 11 participating health centres. 

Study Site: Tororo Hospital, Tororo District

Collaborators: Uganda Heart Institute (UHI)

Principal Investigators: PI- Joselyn Rwebembera, Co-PI Sarah deLoizaga Carney

Study Sponsor: Children’s Hospital Medical Center (“CHMC”)

DPSP Study: Optimal chemopreventive regimens to prevent malaria and improve birth outcomes in Uganda (Optimizing IPTp in Uganda).

Study period:Ongoing.

The “Optimizing IPTp in Uganda” study (DPSP study) is a double-blind randomized controlled trial seeking to assess the benefits of combining sulfadoxine-pyrimethamine (SP) and dihydroartemisinin-piperaquine (DP) for intermittent preventive treatment of malaria in pregnancy (IPTp).

Malaria in pregnancy is a major public health problem in sub-Saharan Africa, where it has been associated with adverse birth outcomes, including spontaneous abortions, preterm births, low birth weight, stillbirths, and neonatal deaths. The World Health Organization recommends IPTp with SP, a broad-spectrum antibiotic as well as an antimalarial, as one of the main interventions to improve birth outcomes. However, the effectiveness of SP for IPTp is compromised by widespread resistance of malaria parasites to SP. Studies evaluating alternative drugs for IPTp have shown DP to be a promising alternative.

Compared to IPTp-SP, IPTp-DP has been shown to significantly reduce the risk of malaria parasitemia during pregnancy and placental malaria at delivery. However, IPTp-DP has not been shown to significantly reduce the risk of adverse birth outcomes compared to IPTp-SP. This could possibly be due to additional protective effects of SP on non-malaria causes of adverse birth outcomes.

We hypothesize that IPTp with a combination of SP+DP will improve birth outcomes compared to IPTp with either SP or DP alone. To test this hypothesis, we are conducting a double-blind, randomized trial in 2757 HIV-negative pregnant women residing in Busia, Uganda, who will be randomized to receive one of the three IPTp arms: 1) monthly IPTp with SP, 2) monthly IPTp with DP, and 3) monthly IPTp with SP + DP. Enrolled pregnant women will be followed through delivery.

Specifically, the study seeks to:

1. Compare the risk of adverse birth outcomes (spontaneous abortion, preterm births, low birth weight, small for gestation age, stillbirth, and neonatal death) among pregnant women randomized to receive monthly IPTp with SP vs. DP vs. SP+DP.;
2. Compare safety and tolerability of IPTp regimens among pregnant women randomized to receive monthly IPTp with SP vs. DP vs. SP+DP.;
3. Compare risks of malaria-specific (clinical malaria, placental malaria) and non-malarial outcomes (reproductive tract infections) among pregnant women randomized to receive monthly IPTp with SP vs. DP vs. SP+DP.

Study site: Masafu General Hospital, Busia

Collaborators:
Principal Investigators: Moses Kamya,Grant Dorsey and Philip Rosenthal
Project Manager: Dr Abel Kakuru
Project Coordinator: Dr Jimmy Kizza
The study is conducted by: collaborators from Makerere University College of Health Sciences, University of California San Francisco, Stanford University, and the Infectious Diseases Research collaboration.
The study will be conducted from 2020-2024.

I AM GOLD:

Study period:Ongoing.

I AM GOLD: The Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study is a multi-cohort study whose goal is to;
Examine airway microbial communities (the lung microbiome) and inflammatory gene expression markers at the time of acute infection and during chronic stable disease that are associated with HIV-associated COPD and lung function decline in HIV and to perform integrative analyses of the airway microbiome, microbial and human transcriptome, metabolome and lung radiographic changes in HIV+ COPD.

Sub studies

• TB-MBLA: This a cross-sectional study with an aim to Investigate the diagnostic and treatment monitoring accuracy of the Molecular Bacterial Load Assay (MBLA)among TB presumptive adults in reference to conventional methods in detecting TB causative agents including sputum smear microscopy, GeneXpert and culture.
• BIOFIRE: A cross-sectional study aimed at evaluating diagnostic performance of Film Array Pneumonia panel test compared to conventional methods in detecting pneumonia causative agents and their antimicrobial susceptibility patterns on sputum samples from HIV+ patients.

Uganda I AM OLD-DA Study (Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities).

Study period: July 1, 2015-April 30, 2025.

The I AM OLD-DA Study is a multi-cohort study with clinical sites in Kampala, Uganda (and San Francisco, CA, USA) whose goal is to examine potential mechanisms for the development of obstructive lung disease and progression of airflow obstruction and diffusion abnormalities in a cohort of HIV-infected subjects recovered from opportunistic pneumonia.

The widespread use of antiretroviral therapy has changed HIV/AIDS from a near-universally fatal disease to a chronic medical condition with near-normal life expectancy in HIV-infected individuals responding to antiretroviral therapy. As a result, persons with HIV/AIDS develop medical conditions such as chronic obstructive pulmonary disease (COPD), typically seen in older individuals. COPD is an HIV-associated lung disease and a leading cause of morbidity and mortality, and its clinical significance is increasing as the HIV population ages worldwide. Despite this, our understanding of the mechanisms underlying HIV-associated COPD is limited, but both HIV-related and COPD- specific mechanisms are hypothesised. An improved account is critical for developing new therapies to treat or prevent this growing problem.

This study builds upon a novel, established multinational (Uganda and US) cohort of persons with HIV/AIDS who recovered from acute opportunistic pneumonia, including tuberculosis (TB). Our data show that different markers are associated with additional lung function abnormalities, suggesting that these abnormalities may be due to different underlying mechanisms. Interestingly, cytomegalovirus (CMV), which is a chronic viral infection common in HIV+ persons, has been associated with the three markers most strongly associated with one of the lung function abnormalities.

These data lead to the following specific aims:

Aims 1 and 2: To test the hypothesis that persistent abnormalities in selected markers of immune activation, inflammation, lung injury, and cellular ageing measured in the blood are associated with subsequent changes (declines) in lung function and that the specific markers associated with each lung function abnormality will be different. The longitudinal study design will strengthen the causal inferences from our earlier work. It will set the foundation for future trials of therapeutic interventions, including the potential for personalised medicine with potentially novel and/or different therapies for different biomarkers and/or lung function abnormalities.

Aim 3: In a cross-sectional subset of HIV-infected participants selected to undergo bronchoscopy and collect lung specimens, to test the hypothesis that abnormalities in the same markers but now measured in lung specimens are associated with abnormal lung function and test the hypothesis that asymptomatic CMV co-infection is also associated with lung function abnormalities and is mediated by these markers. This aim will determine whether CMV co-infection is involved in lung function abnormalities and potentially set the stage for trials of anti-CMV therapy in HIV-associated COPD.

To address these aims, we will conduct a longitudinal study of 400 HIV-infected subjects (200 in the US and 200 in Uganda) and collect and bank blood specimens simultaneously with lung function testing. We will also perform bronchoscopy in a subset of 80 subjects (40 in the US and 40 in Uganda) and collect and bank lung specimens and specimens to assess for CMV co-infection at the same time as lung function testing. The banked samples will allow efficient future testing of new and novel markers. Our long-term objective is to improve our mechanistic understanding of lung function abnormalities in persons with HIV. This would lead to a future study that tests new treatments for this critical and growing clinical problem.

Study site: China-Uganda Friendship Hospital-Naguru, Kampala

Collaborators: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, and the University of California San Francisco.

Principal Investigators: William Worodria

Study Sponsor: National Institutes of Health (NIH). National Heart, Lung, and Blood Institute (NHLBI)

Uganda I AM GOLD Study (Integrated Analysis of Microbial and Genomic Data in Obstructive Lung Disease).

Study period: September 15, 2019-July 31, 2024.

The I AM GOLD Study is a multi-cohort study with clinical sites in Kampala, Uganda (and San Francisco, CA, USA) whose goal is to examine potential microbial and host mechanisms for the development of obstructive lung disease and progression of airflow obstruction and diffusion abnormalities in a cohort of HIV-infected subjects recovered from opportunistic pneumonia. I AM GOLD enrols a subset of participants enrolled in I AM OLD-DA

Our central hypothesis is that enhanced Th17-driven inflammation and chronic Gammaproteobacteria-dominated airway microbiota interact to contribute to obstructive lung disease in HIV-infected individuals. In HIV-uninfected patients with COPD, we have found that a genomic signature of Th17-driven airway inflammation marks a subgroup with functional small airway disease thought to precede emphysema. Second, Th17-driven inflammation, a pathway classically thought to defend against bacteria, is enhanced in the airways of HIV-infected patients. Third, our group has shown that amongst Ugandan HIV-infected patients with pneumonia, a population at higher risk for lung function decline, subgroups are characterised by distinct lower airway microbial communities with differing immune responses. One subgroup had Pseudomonadaceae-dominated airway microbiota and inflammatory gene expression. Gammaproteobacteria, which includes Pseudomonas, are commonly found in COPD and, as with Th17 inflammation, are associated with emphysema. Thus, the Pseudomonadaceae-dominant pneumonia subgroup may be at higher risk for developing chronic disease in continued dysbiosis and low-level Th17-driven chronic inflammation.

These data lead to the following specific aims:

Aim 1: To identify the airway microbial communities and inflammatory gene expression markers during acute infection associated with subsequent incident COPD and lung function decline in persons with HIV/AIDS.

Aim 2: To identify the airway microbial communities and inflammatory gene expression markers during chronic stable disease enhanced in HIV-associated COPD compared to participants without COPD.

Aim 3: To perform integrative analyses of the airway microbiome, microbial and human transcriptome, metabolome and lung radiographic changes in HIV+COPD.

Study site: China-Uganda Friendship Hospital-Naguru, Kampala

Collaborators: Infectious Diseases Research Collaboration, Makerere University College of Health Sciences, and the University of California San Francisco
Principal Investigators: Laurence Huang, William Worodria, Susan Lynch, and Stephanie Christenson

Study Sponsor: National Institutes of Health (NIH). National Heart, Lung, and Blood Institute (NHLBI)

IBIS-Health

Study period:Ongoing.

The overall objective of the IBIS-Health Study (Innovative Incentive Strategies for Sustainable HIV Testing and Antiretroviral Treatment) is to generate evidence on how best to use low-cost incentives to promote HIV testing among men and high-risk adults and to maximize the benefits of ART among HIV-infected adults in rural Uganda. IBIS-Health uses randomized controlled trials and qualitative research to critically evaluate the sustainability of such interventions.

Objectives

1. Assess the comparative effectiveness of lottery, loss aversion, and fixed incentives for increasing HIV testing among men.
2. Determine whether HIV-infected men and women are more likely to achieve and maintain HIV virologic suppression if offered financial incentives vs. no incentives (standard of care).
3. Assess the comparative effectiveness of deposit contracts (a form of incentives that leverages loss aversion) vs. gain-framed incentives, compared to no incentives (control), to promote repeat HIV testing among high-risk HIV-uninfected adults.

• Principal Investigator: Dalsone Kwarisiima, Harsha Thirumurthy, Moses R. Kamya

• Co-Investigators: Gabriel Chamie, Carol Camlin,Diane V. Havlir

• Project Manager: Kara Marson

• Project Coordinator:Alex Ndyabakira,

INTEGRATED HIV/HTN Project:

Leveraging the HIV Platform for Hypertension Control in Uganda.

Study Period: March 2020-February 2025

INTEGRATED HIV/HTN (Leveraging the HIV Platform for Hypertension Control in Uganda) is a five-year project funded by the Second European and Developing Countries Clinical Trials Partnership (EDCTP2) Grant Number: CSA2018HS-2518 to test the effectiveness of an integrated HIV/HTN care model in 26 districts in south-western Uganda. This project is implemented by a consortium led by the Infectious Diseases Research Collaboration (IDRC) in collaboration with the London School of Hygiene and Tropical Medicine (LSHTM), the Uganda Heart Institute (UHI), the Ministry of Health Uganda (MoH) and Makerere University.

There is a high burden of hypertension among HIV and non-HIV-infected people in Uganda, ranging from 15-30%. Yet, the capacity to diagnose, treat and prevent hypertension (HTN) remains sub-optimal. The double jeopardy of HIV and hypertension likely increases the risk of complications such as stroke, coronary artery disease and kidney failure. Less than 5% of people with hypertension are thought to receive regular care; thus, increasing access to care will require its integration into primary health care and HIV clinics, thus reducing co-occurring hypertension-related morbidity and mortality

The project will evaluate the effectiveness of the integrated HIV and HTN care model in selected districts and health facilities in South Western Uganda. It aims at increasing awareness of hypertension, improving hypertension control and improving quality of life for HIV patients and non-infected populations in an integrated manner and ultimately contribute to reducing the overall prevalence of hypertension in Uganda.

Objectives 

• Determine the effectiveness of the integrated HIV/HTN care model on HTN screening, HTN control and dual HIV/HTN control in the HIV clinics;
• To assess the barriers and facilitators of the integrated HIV/HTN care model among National Disease Control Programs, middle-level health district managers, clinic-level PHC leaders, providers, and patients; and
• Determine the cost, cost-effectiveness and incremental gain costs of the integrated HIV/Hypertension care model approach.

Study Site:  96 districts in Ankole, Kigezi, Bunyoro- Tooro

Collaborators: Infectious Diseases Research Collaboration (IDRC), Uganda Ministry of Health (MoH), Makerere University, London School of Hygiene & Tropical Medicine (LSHTM) and Uganda Heart Institute (UHI)

Principal Investigator: Jane Kabami 

Study Sponsor: EDCTP

Novartis Phase 2

Study period:Ongoing.

This study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated P. falciparum malaria. There is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden.

Objectives

• To determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by P. falciparum. The primary efficacy endpoint is the polymerase chain reaction (PCR)corrected adequate clinical and parasitological response(ACPR) at Day 29.
• To evaluate the safety and tolerability of KAF156/LUM-SDF.
• To further assess the effect of treatment with KAF156/LUM-SDF by assessing uncorrected ACPR and corrected ACPR at additional time points, as well as fever- and parasite clearance times.
• To assess key pharmacokinetic(PK) parameters of KAF156 and lumefantrine.

Novartis Phase IIa

Study period:Ongoing.

KAE609 will be evaluated primarily for hepatic safety of single and multiple doses in sequential cohorts with increasing doses. This study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients.

Objectives

• To characterize hepatic safety aspects of single-and multiple ascending doses of KAE609 in adult malaria patients..
• To evaluate overall safety and tolerability of KAE609.
• To assess key pharmacokinetic (PK)parameters following treatment with KAE609.
• To assess the efficacy of KAE609 in patients with uncomplicated falciparummalaria.
• To assess recrudescence after single and multiple doses of KAE609.

PRISM: Program for Resistance, Immunology, Surveillance & Modeling of Malaria in Uganda

Study period: July 2017 to April 2025

Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) is a malaria research program and represents the East African region for the International Center of Excellence for Malaria Research (ICEMR) network. The International Center of Excellence for Malaria Research program was created by NIAID/NIH in July 2010, and established a global network of independent research centers in malaria-endemic settings to provide knowledge, tools, and evidence-based strategies to support researchers working in a variety of settings, especially within governments and healthcare institutions. The overall strategy of the multi-project PRISM program is to apply a comprehensive and iterative approach to malaria Surveillance that will generate an evidence base to help maximize the impact of control interventions across a wide range of epidemiological settings. The program will consist of three research projects linked together in an integrated manner to maximize scientific discovery:

1. 1. Research project 1 (Resistance project) will use samples collected over time at multiple sites to characterize the evolution of phenotypic and genotypic markers of drug and insecticide resistance and assess the impacts of these markers on malaria transmission.

1. 1. Research project 2 (Epidemiology project) will use longitudinal samples from cohorts to characterize factors that determine whether sporozoite inoculation results in the establishment of blood stage infection and characterize factors affecting the duration, density, and clinical consequences of blood stage infections.

1. 1. Research project 3 (Transmission project) will use cohort samples to determine factors associated with gametocyte production and development, evaluate infectivity of the human host to mosquito vectors, and characterize the human infectious reservoir.

These highly interrelated projects will be conducted in settings with varied malaria epidemiology and differing population level control intervention to provide critical information needed to optimize strategies for the control and ultimate elimination of malaria in Uganda.

ABOUT PULESA

Strengthening the Blood Pressure Care and Treatment Cascade for Ugandans Living with
HIV–Implementation Strategies to SAve Lives (PULESA-Uganda) study is an implementation
science study whose aim is to improve hypertension care among people living with HIV
(PLHIV) in urban and peri-urban Uganda in a scalable and sustainable pattern. The study is
evaluating two strategies for integrating hypertension and HIV services in 16 HIV clinics in
Kampala and Wakiso Districts.

The study is being led by Infectious Diseases Research Collaboration in collaboration with
Makerere University College of Health Sciences, the Uganda Heart Institute, Yale University,
University of Washington, Research Triangle International and the Uganda Ministry of
Health.

There are two phases for implementation, the first phase was a formative study whose
overall objective was to assess patients’ and health care providers’ knowledge, attitudes,
practices, and routines relating to hypertension and barriers and facilitators to
implementation of integrated HIV-hypertension care in HIV clinical settings.

The second phase is a stepped wedge cluster randomized trial of 16 HIV clinics in Kampala
and Wakiso districts, whose overall objective is to determine the effectiveness and evaluate
the implementation strategy’s economic and financial sustainability of two strategies for
integrating HIV-hypertension.

The implementation strategies are;
1) The HTN-BASIC intervention will consist of providing consistent access to diagnostic
equipment and evidence-based antihypertensive drugs at no cost to the PLHIV with
hypertension. A consistent supply of three anti-hypertensive drugs will be supplied to each
clinic in the trial.

2) The HTN-PLUS intervention will have all the components of HTN-BASIC but will also
include a more intensive package of activities for clinic staff, including training on
hypertension management, adoption of differentiated service delivery for hypertension,
remote patient monitoring, and a performance improvement program. This enhanced
intervention was developed by the team in consultation with clinicians, healthcare
managers and policy makers through a human-centered design process.

Sixteen clinics will be randomized to the order in which they will begin intervention, with
two clinics initiating the intervention every two months after a run-in period. Clinic data will
be collected during the control period, run-in period, and the intervention phase, and an
additional longitudinal cohort study will continue for a few months after the intervention
phase has concluded to gather more granular detail on how hypertension care is being
implemented at the HTN-BASIC and HTN-PLUS sites.

Study objectives are: –
1. To evaluate the effectiveness of two strategies for integrating HIV-Hypertension in 16 HIV
clinics in Kampala and Wakiso.
2. To determine the implementation outcomes of two implementation strategies
3. To evaluate the economic and financial sustainability of the integrated care strategies

Study Site: 16 HIV clinics (Eight in Wakiso and Eight clinics in Kampala) Collaborators: Infectious Diseases Research Collaboration (IDRC), Uganda Ministry of Health (MoH), Makerere University, Uganda Heart Institute (UHI), University of Washington, Yale University and Makerere University Joint AIDS Program (MJAP)

Principal Investigators: Fred C. Semitala; (Contact PI)
Chris T. Longenecker; MPI

Study Sponsor: National Heart Lung and Blood Institute (NHLBI) of National
Institute of Health (NIH) with partnership Fogarty International Center (FIC) under the
grant UH3-HL-154501.

“SEARCH SAPPHIRE”—A Multi-sectoral Strategy to Address Primary and Persistent drivers of the HIV epidemic in Rural East Africa.

Study period:Ongoing.

Funded by NIH, SAPPHIRE was designed to conduct population-level research to evaluate strategies to deliver HIV prevention and treatment better to all persons in need and leverage the HIV care system for other chronic diseases to further reduce HIV incidence and improve health. Overall, SAPPHIRE aims to determine how to reduce HIV incidence to below 0.1% using innovative strategies for HIV prevention and treatment to simultaneously reach “persistent driver” populations with scalable interventions.

Over a 5-year period (phase A 2-years and phase B 3-years), an estimated 162,400 individual participants ≥15 years of age both the positive for HIV and those at risk of acquiring HIV living in 36 communities in rural western Kenya and rural western Uganda will be enrolled into SAPPHIRE trial.

• Phase A will have 7 individual-level randomized trials to assess effectiveness, fidelity and cost and improve context-specific “fit” of prevention and treatment interventions. Combining effectiveness with implementation, costing and modelling outcomes, Phase A will optimize intervention packages with context specific adaptations in structured consultation with stakeholders.
• Phase B, which will evaluate the effects of these optimized dynamic prevention and treatment packages, alone and in combination, on prevention coverage, population-level suppression, and HIV incidence, as well as other health outcomes, in a balanced, community randomized 2×2 factorial design.

Collaborators:
The study Principal Investigators are Professor Moses Kamya at Makerere University and IDRC, Uganda; Professor Maya Petersen at University of California, Berkeley, USA; and Professor Diane Havlir at UCSF, USA.
The project will be implemented by the Infectious Diseases Research Collaboration (IDRC), Makerere University in Uganda and KEMRI in Kenya alongside partners from the University of California, San Francisco Research Collaboration.

TB Screening Improves Preventive Therapy Uptake Trial (TB-SCRIPT)

Study Period: November 2020- March 2025

Overview

Tb-script is a groundbreaking research initiative to evaluate the clinical impact of Point-of-Care (POC) C-reactive protein (CRP) based TB screening on immediate and longer-term outcomes of individuals living with HIV. This pragmatic single-blinded, randomised-controlled Phase III trial is conducted at four prominent clinics in Kampala, Uganda. 

Aims of the trial. 

Overall aim: The overall objective of this randomised trial is to evaluate the effectiveness and cost-effectiveness of POC CRP-based TB screening 

Specific aims of the trial

Aim 1: Compare the impact of point-of-care C-reactive protein (POC CRP)- vs. symptom-based TB screening on 2-year patient outcomes.

Aim 2: Compare the impact of POC CRP-   vs symptom-based TB screening on TB preventive therapy (TBPT) uptake and TB case detection.

Aim 3: Compare cost, cost-effectiveness, and projected epidemiological impact of POC CRP- vs. symptom-based TB screening.

Who is funding the trial?

The National Heart Lung and Blood Institute of the National Institute of Health, USA funds the trial. 

Research outputs. 

1. Chaisson LH, Semitala FC, Mwebe S, et al. Transaminitis prevalence among HIV-infected adults eligible for tuberculosis preventive therapy. Aids. 2022;36(11):1591-5.
2. Semitala FC, Chaisson LH, Dowdy DW, et al. Tuberculosis screening improves preventive therapy uptake (TB SCRIPT) trial among people living with HIV in Uganda: a study protocol of an individual randomised controlled trial. Trials. 2022;23(1):399.
3. Chaisson LH, Semitala FC, Nangobi F, et al. Viral suppression among adults with HIV receiving routine dolutegravir-based antiretroviral therapy and three months’ weekly isoniazid-rifapentine. Aids. 2023;37(7):1097-101.

Further information can be accessed in the protocol at the reference below

Semitala FC, Chaisson LH, Dowdy DW, et al. Tuberculosis screening improves preventive therapy uptake (TB SCRIPT) trial among people living with HIV in Uganda: a study protocol of an individual randomised controlled trial. Trials. 2022;23(1):399.

Study Site: Kawaala KCCA Health Centre IV, Kitebi KCCA Health Centre III, TASO Mulago and Mulago Immune Suppression Syndrome (Mulago ISS Clinic)

Collaborators: University of California San Francisco (UCSF)

Principal Investigators: PI- Joselyn Rwebembera

Study Sponsor: National Heart Lung and Blood Institute of the National Institute of Health (NIH), USA