Rheumatic Heart Disease School Project

November 11, 2019 updated by: University Hospital Inselspital, Berne

A Population-Based Study of Prevalence of Rheumatic Heart Disease and Cardiovascular Outcomes Among Schoolchildren in Nepal

Acute rheumatic Fever (ARF) results from an autoimmune response due to molecular mimicry between the M-protein on the group A β-hemolytic streptococci (GABHS) cell membrane and cardiac myosin, and may lead through recurrent or sustained inflammation to Rheumatic Heart Disease (RHD). RHD remains a major contributor to morbidity and premature death in the working age population in Nepal. Secondary prevention with regular oral or intravenous administration of penicillin continued until early adulthood is recommended to prevent the progression of the development of endocarditis and subsequent valvular dysfunction.

Screening for rheumatic heart disease using echocardiography has the potential to detect rheumatic valvular lesions at an earlier, clinically silent stage, as compared to clinical examination alone and might have a beneficial impact on long-term outcome of children with RHD. Schoolchildren aged 5-16 years from several public and private schools from rural and urban areas in Southeastern Nepal will be screened for RHD using portable echocardiography.

Three main inter-related objectives will be pursued in three phases of the study: In a first phase using a cross sectional approach, the prevalence of clinical and subclinical RHD will be investigated among a representative sample of schoolchildren from public and private schools in urban and rural areas. In a second phase, using a cohort study approach among those children diagnosed at different stages of RHD, clinical outcomes with regular medical surveillance will be assessed (a), and clinical and social risk factors associated with prognosis of the disease after receiving medical care at various stages of disease at diagnosis will be determined (b). A third phase will integrate the prevalence rates from phase 1 and the clinical outcomes from phase 2 in a mathematical model to assess the impact of screening and RHD treatment on health resource utilization.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background

Acute rheumatic Fever (ARF) results from an autoimmune response due to molecular mimicry between the M-protein on the group A β-hemolytic streptococci (GABHS) cell membrane and cardiac myosin, and may lead through recurrent or sustained inflammation to Rheumatic Heart Disease (RHD) (1). RHD is reported to affect over 15 million people worldwide and remains a major contributor to morbidity and premature death in the working age population in developing countries (2). Socioeconomic determinants such as poverty, overcrowding, and malnutrition have been related to RHD. The prevalence of ARF and RHD seems to be particularly high in Southeast Asia, the Western Pacific and Africa (3). Whereas heart murmurs detected on clinical examination may indicate clinically manifest RHD, echocardiographic screening revealed ten times higher prevalence rates of RHD among schoolchildren (4) and may help diagnose RHD at an earlier, "clinically silent" stage.

Patients with a past medical history of ARF or RHD are recommended secondary prevention with regular oral or intravenous administration of penicillin continued until early adulthood.

Even though preventive measures with penicillin are inexpensive and efficient, this strategy is difficult to effectuate in developing countries with limited access to health care resources.

A recent study proved that enrolling patients with ARF and RHD in a registry with close follow-up increases compliance to treatment and thus helps in reducing the cardiovascular sequelae associated with disease progression (5).

The prevalence of RHD among schoolchildren in urban and rural areas in Nepal is largely unknown, and risk factors associated with prognosis of the disease after receiving medical care at various stages of disease at diagnosis need to be determined. Moreover, the impact of screening using echocardiography, detecting RHD at an earlier, "clinically silent" stage of RHD on health resource utilization has to be determined.

Objective

Originally, three main inter-related objectives were to be pursued in three phases of the study: In the first phase using a cross sectional approach, the prevalence of clinical and subclinical RHD were to be investigated among a representative sample of schoolchildren from public and private schools in urban and rural areas. In the second phase, using a cohort study approach among those children diagnosed at different stages of RHD, clinical outcomes with regular medical surveillance were to be assessed (a), and clinical and social risk factors associated with prognosis of the disease after receiving medical care at various stages of disease at diagnosis were to be determined (b). A third phase was to integrate the prevalence rates from phase 1 and the clinical outcomes from phase 2 in a mathematical model to assess the impact of screening and RHD treatment on quality of life and health resource utilization.

On August 14 2013, the Nepal Health Research Council required the introduction of a control group in the design of the Rheumatic Heart Disease (RHD) School Project. The original design included a random sampling stratified by urban versus rural location and public versus private status of schools, with a computer-generated random sequence used to determine which schools would be centrally selected during Phase 1 of the project to undergo screening for RHD. The original computer-generated random sequence was therefore used to determine which schools would be randomly selected as control schools which did not undergo the screening intervention during Phase 1, but would be selected for follow-up during Phase 2 of the project. This approach implicitly allowed for a cluster randomized comparison between intervention and control schools at follow-up in children aged 5 to 12 years at baseline, when phase 1 of the study took place.

Methods

The project will employ three types of study designs performed in sequential phases: a cross sectional study (part 1), a longitudinal cohort study (part 2) and an analysis of the impact of screening, secondary prevention and treatment on health resource utilization (part 3).

  1. Part 1: Cross-Sectional Survey Schoolchildren aged 5-16 years will be screened at selected schools in the Southeast area of Nepal. A follow-up examination will be performed in a subset of schools that underwent screening at baseline and in all control schools, allowing for a cluster randomized comparison at follow-up between schools that underwent screening at baseline and control schools in children aged 5 to 12 years at baseline.
  2. Part 2: Longitudinal Cohort Study Those children with documented history of ARF and/or RHD will be included into a prospective registry and receive secondary prevention will be followed on a regular basis.
  3. Part 3: Impact of Screening and Treatment of RHD The third phase will integrate the prevalence rates from phase 1 and the clinical outcomes from phase 2 in a mathematical model to assess the impact of screening and RHD treatment on health resource utilization.

Study Type

Interventional

Enrollment (Actual)

8519

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Nepal
    • Dharan
      • B.P. Koirala Institute Of Health Sciences (bpkihs), Dharan, Nepal, 765000
        • Department of Internal Medicine and Cardiology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 16 years (Child)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Schoolchildren in Southeast Nepal aged 5-16 years
  • Written informed consent by the principal of the school
  • Passive consent from the parents

Exclusion Criteria

  • No formal exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Arm
Echocardiographic screening
Diagnostic test: Echocardiography
No Intervention: Control Arm
No echocardiographic screening

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Prevalence of Rheumatic Heart Disease
Time Frame: 12 Months Screening Period
12 Months Screening Period

Secondary Outcome Measures

Outcome Measure
Time Frame
composite of all-cause mortality, stroke, endocarditis, hospitalization for congestive heart failure, valvular surgery, mitral balloon valvuloplasty, and recurrence of rheumatic fever
Time Frame: 5 years
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Inselspital, Berne

Collaborators

B.P. Koirala Institute of Health Sciences

Investigators

  • Principal Investigator: Thomas Pilgrim, MD, Department of Cardiology, Bern University Hospital, Switzerland
  • Principal Investigator: Nikesh R Shrestha, MD, FESC, Department of Internal Medicine and Cardiology, B.P. Koirala Institute of Health Sciences (BPKIHS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2012

Primary Completion (Actual)

January 3, 2019

Study Completion (Actual)

April 30, 2019

Study Registration Dates

First Submitted

March 7, 2012

First Submitted That Met QC Criteria

March 8, 2012

First Posted (Estimate)

March 9, 2012

Study Record Updates

Last Update Posted (Actual)

November 13, 2019

Last Update Submitted That Met QC Criteria

November 11, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 018/12

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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