Clinical Research Directory

GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial

The goal of this clinical trial is to determine if twice daily oral penicillin prophylaxis is non-inferior to monthly IM penicillin prophylaxis in preventing latent Rheumatic Heart Disease Progression in children between the ages of 5-17 years. The main objective is to compare the proportion of children aged 5-17 years with latent RHD receiving oral penicillin prophylaxis who progress to worse valvular disease at 2-years compared to children who receive IM penicillin prophylaxis.

Echocardiographic Screening of Pregnant Women During Antenatal Care

Non-obstetrical drivers of adverse pregnancy outcomes are underappreciated. Latent structural heart disease may account for a substantial proportion of adverse pregnancy outcomes in low-resource settings. Pregnant women presenting to B.P. Koirala Institute of Health Sciences will be prospectively included into a registry upon their visit for antenatal care. Women will be followed until 6 weeks after the time of delivery. Nested within this registry, the investigators will perform a registry-based adaptive cluster randomized crossover trial. The trial compares an experimental condition (echocardiographic screening) and a control condition (routine antenatal care).

A Non-Inferiority Trial of Stopping Penicillin in Early Rheumatic Heart Disease: GOAL-Stop

GOAL-Stop is a randomized, controlled, non-inferiority trial designed to evaluate whether discontinuing secondary antibiotic prophylaxis (SAP) is non-inferior to continuing SAP in preventing progression of rheumatic heart disease (RHD) among children and adolescents. The trial will enroll participants aged 5-20 years with previously diagnosed mild RHD who have received at least 2 years of SAP and who demonstrate either echocardiographic normalization or stability (persistent mild RHD). Participants will be randomized to either continue SAP or discontinue SAP for 2 years. The primary outcome is echocardiographic progression of RHD at 2 years, assessed by blinded adjudicators using the 2023 World Heart Federation criteria. Subgroup analyses will evaluate outcomes in participants with echocardiographic normalization versus stable mild RHD, and an exploratory analysis will assess whether outcomes differ by prior prophylaxis route (oral vs. intramuscular).

Vitamin K Antagonist in Rheumatic Heart Disease Patients With Mechanical Heart Valves: Our Current Status

VKA in RHD patients with MHV: our current status

Clinical Trial Phase I/IIa to Evaluate the Safety and Immunogenicity of StreptInCor

This is a Phase I/IIa, randomized, double-blind, placebo-controlled, dose-escalation clinical trial to test the candidate vaccine StreptInCor. The study will include four different doses (25 µg, 50 µg, 100 µg, and 200 µg) of StreptInCor produced under Good Manufacturing Practices (GMP) and formulated with aluminum hydroxide as the vaccine adjuvant. The adjuvant alone will be used as a placebo in this trial. Five groups, each consisting of twelve healthy adult volunteers, will randomly receive two doses of the vaccine or placebo with a 28-day interval, along with a booster dose six months after the initial vaccination

Korea VHD Echo Study: Surveillance of Aortic, Mitral & Tricuspid Patients - Insights From Real-world Practice

Valvular heart disease (VHD) is a growing public health concern globally, with increasing disease burden and rising interest in advanced treatment strategies such as transcatheter interventions. However, there remains a significant lack of real-world data regarding echocardiography practices, disease prevalence and progression, referral patterns, and treatment pathways. Addressing these gaps is critical for improving patient care and informing clinical decision-making. South Korea provides a unique opportunity to conduct a nationwide retrospective echocardiographic study due to its advanced healthcare infrastructure, high patient volume, and strong tradition in clinical research. The current study aims to evaluate the real-world burden and clinical journey of patients with moderate or severe valvular disease over a 10-year period, based on echocardiographic and electronic medical record (EMR) data collected from multiple tertiary centers across the country.

Effectiveness of Edutainment-Based Interventions in Increasing Knowledge of Rheumatic Fever and Rheumatic Heart Disease Among School-Going Children in Nepal: Study Protocol for Colors to Save Hearts Quasi-Experimental Pretest-Posttest Study

Background: Acute rheumatic fever (ARF) and its sequela, rheumatic heart disease (RHD), remain significant public health concerns in low- and middle-income countries, including Nepal. Despite their preventable nature, awareness of ARF and RHD among schoolchildren is limited. Innovative, age-appropriate health education strategies are urgently needed to promote early recognition and prevention. Objective: This study aims to evaluate the effectiveness of an edutainment-based intervention in improving knowledge of ARF and RHD among school-going children in Nepal. Methods: A quasi-experimental pretest-posttest study design with a waitlist control group will be employed across 24 public schools in six diverse districts. A total of 2,400 students from Grades 6 to 9 will be included. The intervention integrates creative educational tools-coloring books, activity books, storytelling, videos, and interactive sessions-tailored to different age groups. Knowledge change will be measured using a validated questionnaire administered at baseline and post-intervention. Secondary outcomes include the prevalence of RHD-related symptoms assessed through clinical screening. Expected Outcomes: It is hypothesized that students in the intervention group will demonstrate a statistically significant improvement in knowledge scores compared to their baseline levels and the control group. The study will also assess the feasibility and acceptability of the intervention and inform recommendations for broader school-based health education programs. Conclusion: This study addresses a critical gap in child health education in Nepal using an innovative, scalable approach. Findings will contribute to the evidence base for integrating edutainment into school curricula to combat preventable diseases like RHD in resource-limited settings.

Accelerating Delivery of rheUmatic Heart Disease Preventive iNterventions in Northern Uganda

The goal of this prospective study is to evaluate the feasibility, sustainability, and public health impact of a district-based program for secondary prevention of Rheumatic Heart Disease (RHD) in Uganda.

The Clinical Influence of Developing a Sustainable Cardiac Surgery Service to Reduce the Burden of Rheumatic Heart Disease in Sub-Saharan Africa

In this bi-directional program of education, training and research activities based on sustainable development goals aim is to develop cardiac surgery service in Ethiopia. The aim is to evaluate the short and long-term outcome of cardiac surgery for rheumatic heart disease in a low-income country compared to individuals not offered cardiac surgery due to limited availability of the service. Second aim is to evaluate the quality of anticoagulant therapy in patients after cardiac surgery for rheumatic heart disease in a low-income country .

Treating Severe Mitral Valve Annular or Valvular Calcification Using Shockwave Balloon SMARTWAVE

Mitral stenosis (MS) is a heavily symptomatic valvular heart disease. Common causes of MS included chronic rheumatic heart disease (CRHD) and mitral annular calcification (MAC). Current guideline recommends percutaneous balloon mitral valvuloplasty (PBMV) being the first line intervention for rheumatic MS with favorable anatomy. However, severely calcified mitral valve (i.e. those with Wilkins scores\>8) makes the mitral valve non-pliable and carries high risk of severe mitral regurgitation (MR) (4-19%) with conventional balloon valvuloplasty. MAC is an increasingly recognized disease associated with atherosclerotic risk factors, and a well-recognized valve morphology that responses poorly with PBMV. Besides, conventional open-heart surgery for MAC-associated mitral valve dysfunction carries high mortality. Transcatheter mitral valve replacement with valve-in-MAC has become an alternative in treating these patients. However, valve-in-MAC is not always feasible and still carries operative and 30-day mortality. Intravascular lithotripsy is an approved adjunct interventional therapy in treating calcified lesions to facilitate stenotic lesion opening in peripheral vascular disease and coronary artery disease. The off-label use of current peripheral lithotripsy balloon in mitral valve as a compassionate treatment or as an adjunct treatment before mitral balloon valvuloplasty and transcatheter mitral valve replacement has been reported with success . A possible mechanism is that lithotripsy preferentially impacts hard tissue, disrupts calcium, and leaves soft tissue undisturbed, improving valve pliability, preventing leaflet damage, and making subsequent valvuloplasty safer. However, the off-label use of multiple peripheral lithotripsy balloons in mitral valve is technically complicated. SmartWave balloon was specifically designed lithotripsy balloon for calcified aortic stenosis. This first-in-human study aims to apply the SmartWave lithotripsy balloon in treating calcified mitral stenosis due to MAC or severely calcified rheumatic mitral valve.

Screening and Secondary Prevention Rheumatic Heart Disease Study

After basic clinical screening including history and physical, Point of care ultrasound will be performed to look at Mitral, Aortic and Tricuspid Valves for regurgitation or stenosis. For patients with confirmed Rheumatic heart disease (RHD), treatment and referral depending on stage of disease. Antibiotic prescription could be shifted to community health workers delivering preventive medications via practical clinical algorithms, diagnostic tools, availability of appropriate antibiotics, and supportive supervision. Patients will have repeat imaging at 2 years and 5 years to look at the outcome of delayed progression of valve disease.

Rheumatic Heart Disease Research and Screening in Nepal: A Feasibility Study

Rheumatic Heart Disease (RHD) remains a significant public health problem in lower and middle-income countries, accounting for over 300,000 deaths world-wide. RHD is a sequela of Acute Rheumatic Fever (ARF) caused by Group A Streptococcus (GAS). Benzathine Penicillin Prophylaxis (BPP), through tri-weekly intramuscular injection of benzathine penicillin G, remains the mainstay of intervention to delay and prevent the sequelae among ARF and RHD patients by preventing repeat GAS infections. Two major obstacles exist to the optimal utilization of this effort. First, despite proven benefits, BPP adherence remains low. Unfortunately, there is very little knowledge on the factors associated with BPP adherence. Even in countries like Nepal, which has a nation-wide free BPP program serving about 6000 patients, there is absence of a robust system to prospectively track and study these patients. Second, largely because RHD is initially asymptomatic, only a fraction of those who would benefit are enrolled in BPP programs. There is a dearth of information and evidence on potentially high-yield approaches like the screening of first-degree relatives (FDRs) of RHD patients to identify asymptomatic, early-stage RHD patients who may benefit from BPP. The investigators will combine the resources and expertise at the University of Washington with those from existing partners at two leading Nepali hospitals (Manmohan Cardiothoracic Vascular and Transplant Center and Dhulikhel Hospital) to first create an easy to use, scalable, comprehensive electronic RHD registry and enroll BPP patients from these sites. In Aim 1, the investigators will examine whether patient socio-demographic, clinical, and health services-related characteristics are associated with BPP adherence. Investigators will use the BPP registry to collect important covariate information and adherence outcomes to address this aim. In Aim 2, investigators will determine the feasibility of screening FDRs of known RHD patients. Investigators will invite FDRs of known RHD patients (enrolled in the BPP registry) for echocardiographic screening for RHD. Investigators will assess the prevalence of RHD in these FDRs. This proposal harnesses one of the largest RHD patient pools in the world for establishing a robust RHD-related quality improvement and research platform that serves as a solid foundation for conducting larger epidemiologic, interventional, and implementation studies on RHD risk, prevention, and treatment.

Role of Statins In Slowing Rheumatic Heart Disease (RHD) Progression

The goal of this study is to address specific implementation questions necessary and sufficient to ensure the feasibility of the larger randomized trial examining the efficacy of statin medications in slowing rheumatic heart disease (RHD) valvular pathology progression. This feasibility study is intended to confirm the number of readily recruitable subjects, assess recruitment rate, and assess the rate of valve pathology via echocardiograms. These results are necessary and sufficient to facilitate the successful design of a large full scale randomized trial to determine whether statins improve outcomes in RHD. Successful treatment of RHD would fundamentally shift the RHD management paradigm world-wide, improve the lives of millions afflicted with RHD, and subsequently, decrease health care spending on RHD management.

Effectiveness of a School-centered Prevention Program on Prevalence of Latent Rheumatic Heart Disease

The overall objective is to evaluate the effectiveness of a school-centered primary and secondary prevention program on the prevalence of latent rheumatic heart disease among schoolchildren in Nepal, and to investigate the role of socioeconomic and environmental factors in the development and progression of rheumatic heart disease.