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

Primary Purpose

Rheumatic Heart Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
Uganda
Study Type
Interventional
Intervention
phenoxymethyl penicillin
intramuscular benzathine penicillin G (BPG) prophylaxis
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatic Heart Disease

Eligibility Criteria

5 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Has a new diagnosis of latent RHD detected through primary or secondary school echocardiographic screening. Has agreed to participate in the study via the study's informed consent/assent process. Operational Definition of Latent RHD Borderline RHD or Mild Definite RHD (to include no more than mild regurgitation at the mitral or aortic valve, normal mean mitral and aortic valve gradients, normal bi-ventricular function) according to the 2012 WHF consensus criteria. Exclusion Criteria: Known history of ARF or RHD Newly diagnosed RHD by echo screening considered to be "missed clinical RHD" as compared to true latent RHD including: > mild pathological valvular regurgitation at the mitral valve or aortic valve, mitral stenosis (mean MV gradient ≥ 4mmHg) (definite B61), aortic stenosis (mean AV gradient ≥ 20mmHg) Structural or functional cardiac defects, other than those consistent with RHD, that were known prior to or detected through echo screening (except patent foramen ovale, small atrial septal defect, small ventricular septal defect, small patent ductus arteriosus) Self-report of prior allergic reaction to penicillin Any known conditions predisposing to thrombocytopenia or hypercoagulability, or other contraindications to intramuscular injection Any known co-morbid conditions (ex. HIV, renal deficiencies, severe malnutrition) that have resulted in prescription of regular antibiotic prophylaxis)

Sites / Locations

  • Uganda Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Oral Pencillin

IM Penicillin

Arm Description

Oral phenoxymethyl penicillin (Pen V) prophylaxis 250mg twice daily.

Intramuscular benzathine benzylpenicillin G (BPG) prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days

Outcomes

Primary Outcome Measures

Progression
Progression of echocardiographic features of latent RHD to borderline to definite, or definite to mild or definite to moderate/severe

Secondary Outcome Measures

Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin
The aim is to understand the costs and effectiveness of the intervention. Costs will include intervention and disease specific costs, capturing both health system and family out of pocket costs. Participants will complete a questionnaire asking about out-of-pocket cost (medications, supplies, consultation fees) and lost productivity (including missed school and workdays) due to the intervention. Costs will be measured in the local currency (Uganda Shillings) and presented in United States dollars (USD)
Obtain cost data associated with the receipt of oral or IM penicillin in the community from a healthcare provider perspective.
In order to understand health center and community costs, 10 randomly selected health care facilities (including level II, III, and IV facilities) will be surveyed to obtain direct costs of medications, supplies as well as any administration and professional fees associated with outpatient and inpatient visits.
Treatment Acceptance
Treatment acceptance will be assessed with the widely-used Chronic Treatment Acceptance (ACCEPT) questionnaire, a generic medication acceptance instrument validated for chronic conditions. This 25-item survey consists of six areas of focus: medication convenience (3 items), length of treatment (2 items), medication constraints (9 items), medication side effects (5 items), medication effectiveness (3 items), medication advantages (3 items). Responses are rated on a 5-point Likert scale and scores of 1 through 4 indicating increasing levels of acceptance.
Treatment Satisfaction
Treatment Satisfaction will be assessed with the 14-item Abbreviated Treatment Satisfaction Questionnaire (v 1.4). This widely used survey contains 4 areas of focus including satisfaction of treatment effectiveness (3 items), satisfaction with treatment side effects (5 items), satisfaction with treatment convenience (3 items), and a global treatment satisfaction (3 items). Scores are then transformed to a score of 0-100 to create the overall scale score and the subcategory scores, with higher scores representing higher treatment satisfaction on that domain.
Health-Related Quality of Life
Health Related Quality of Life will be measured using the Pediatric Quality of Life Inventory Version 4.0 Generic Core (PedsQL 4.0) questionnaire. The PedsQLTM4.0 is a 23-item survey for children aged 5-18 which assesses HRQOL. It has four areas of focus: Physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), school functioning (5 items). Each item has five possible responses measuring the extent to which the item was a problem during the past month. The possible responses are measured using a 5-point Likert scale from 0=never a problem to 4 = almost always a problem. These reverse scaled scores are then transformed to a score of 0-100 to create the overall scaled score and the subcategory scores, with higher scores representing better quality of life.
Patient-reported outcomes
Interviews will be used to collect qualitative data around participants perceptions of the impact of RHD and its treatment on their activities of daily living and quality of life including experiences with IM or oral penicillin prophylaxis.

Full Information

First Posted
January 4, 2023
Last Updated
May 5, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Uganda Heart Institute
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1. Study Identification

Unique Protocol Identification Number
NCT05693545
Brief Title
GOALIE: Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent RHD Trial
Official Title
Intramuscular vs. Enteral Penicillin Prophylaxis to Prevent Progression of Latent Rheumatic Heart Disease: A Non-inferiority Randomized Trial
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 1, 2024 (Anticipated)
Primary Completion Date
March 31, 2027 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati
Collaborators
Uganda Heart Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
GOALIS is a randomized controlled trial developed to provide high quality contemporary evidence on the efficacy of oral penicillin as RHD prophylaxis. Aim 1: 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. Aim 2: To evaluate the economic equivalence and cost-effectiveness of oral penicillin compared to IM penicillin, after echocardiographic screening for latent RHD detection. Aim 3: Compare patient-reported outcomes (treatment acceptance, treatment satisfaction, and health-related quality of life) between children receiving oral and IM penicillin prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatic Heart Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
1004 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Oral Pencillin
Arm Type
Experimental
Arm Description
Oral phenoxymethyl penicillin (Pen V) prophylaxis 250mg twice daily.
Arm Title
IM Penicillin
Arm Type
Active Comparator
Arm Description
Intramuscular benzathine benzylpenicillin G (BPG) prophylaxis (600,000 IU for children <30kg, 1.2 million IU for children ≥30kg), every 28 days
Intervention Type
Drug
Intervention Name(s)
phenoxymethyl penicillin
Other Intervention Name(s)
Pen V
Intervention Description
Prophylaxis
Intervention Type
Drug
Intervention Name(s)
intramuscular benzathine penicillin G (BPG) prophylaxis
Other Intervention Name(s)
benzathine penicillin G, BPG, penicillin prophylaxis
Intervention Description
Prophylaxis
Primary Outcome Measure Information:
Title
Progression
Description
Progression of echocardiographic features of latent RHD to borderline to definite, or definite to mild or definite to moderate/severe
Time Frame
2 year endpoint
Secondary Outcome Measure Information:
Title
Demonstrate non-inferior costs and cost-effectiveness of oral penicillin compared to IM penicillin
Description
The aim is to understand the costs and effectiveness of the intervention. Costs will include intervention and disease specific costs, capturing both health system and family out of pocket costs. Participants will complete a questionnaire asking about out-of-pocket cost (medications, supplies, consultation fees) and lost productivity (including missed school and workdays) due to the intervention. Costs will be measured in the local currency (Uganda Shillings) and presented in United States dollars (USD)
Time Frame
baseline, 6, 12, 18, 24 months post randomization
Title
Obtain cost data associated with the receipt of oral or IM penicillin in the community from a healthcare provider perspective.
Description
In order to understand health center and community costs, 10 randomly selected health care facilities (including level II, III, and IV facilities) will be surveyed to obtain direct costs of medications, supplies as well as any administration and professional fees associated with outpatient and inpatient visits.
Time Frame
2 year endpoint
Title
Treatment Acceptance
Description
Treatment acceptance will be assessed with the widely-used Chronic Treatment Acceptance (ACCEPT) questionnaire, a generic medication acceptance instrument validated for chronic conditions. This 25-item survey consists of six areas of focus: medication convenience (3 items), length of treatment (2 items), medication constraints (9 items), medication side effects (5 items), medication effectiveness (3 items), medication advantages (3 items). Responses are rated on a 5-point Likert scale and scores of 1 through 4 indicating increasing levels of acceptance.
Time Frame
baseline, 6, 12, 18, 24 months post randomization
Title
Treatment Satisfaction
Description
Treatment Satisfaction will be assessed with the 14-item Abbreviated Treatment Satisfaction Questionnaire (v 1.4). This widely used survey contains 4 areas of focus including satisfaction of treatment effectiveness (3 items), satisfaction with treatment side effects (5 items), satisfaction with treatment convenience (3 items), and a global treatment satisfaction (3 items). Scores are then transformed to a score of 0-100 to create the overall scale score and the subcategory scores, with higher scores representing higher treatment satisfaction on that domain.
Time Frame
baseline, 6, 12, 18, 24 months post randomization
Title
Health-Related Quality of Life
Description
Health Related Quality of Life will be measured using the Pediatric Quality of Life Inventory Version 4.0 Generic Core (PedsQL 4.0) questionnaire. The PedsQLTM4.0 is a 23-item survey for children aged 5-18 which assesses HRQOL. It has four areas of focus: Physical functioning (8 items), emotional functioning (5 items), social functioning (5 items), school functioning (5 items). Each item has five possible responses measuring the extent to which the item was a problem during the past month. The possible responses are measured using a 5-point Likert scale from 0=never a problem to 4 = almost always a problem. These reverse scaled scores are then transformed to a score of 0-100 to create the overall scaled score and the subcategory scores, with higher scores representing better quality of life.
Time Frame
baseline, 6, 12, 18, 24 months post randomization
Title
Patient-reported outcomes
Description
Interviews will be used to collect qualitative data around participants perceptions of the impact of RHD and its treatment on their activities of daily living and quality of life including experiences with IM or oral penicillin prophylaxis.
Time Frame
baseline, 6, 12, 18, 24 months post randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has a new diagnosis of latent RHD detected through primary or secondary school echocardiographic screening. Has agreed to participate in the study via the study's informed consent/assent process. Operational Definition of Latent RHD Borderline RHD or Mild Definite RHD (to include no more than mild regurgitation at the mitral or aortic valve, normal mean mitral and aortic valve gradients, normal bi-ventricular function) according to the 2012 WHF consensus criteria. Exclusion Criteria: Known history of ARF or RHD Newly diagnosed RHD by echo screening considered to be "missed clinical RHD" as compared to true latent RHD including: > mild pathological valvular regurgitation at the mitral valve or aortic valve, mitral stenosis (mean MV gradient ≥ 4mmHg) (definite B61), aortic stenosis (mean AV gradient ≥ 20mmHg) Structural or functional cardiac defects, other than those consistent with RHD, that were known prior to or detected through echo screening (except patent foramen ovale, small atrial septal defect, small ventricular septal defect, small patent ductus arteriosus) Self-report of prior allergic reaction to penicillin Any known conditions predisposing to thrombocytopenia or hypercoagulability, or other contraindications to intramuscular injection Any known co-morbid conditions (ex. HIV, renal deficiencies, severe malnutrition) that have resulted in prescription of regular antibiotic prophylaxis)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ndate Fall, MS RN
Phone
15135171327
Email
ndate.fall@cchmc.org
First Name & Middle Initial & Last Name or Official Title & Degree
Mary Banks
Email
mary.Banks@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Z Beaton
Organizational Affiliation
Cincinnati Chidren's hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Uganda Heart Institute
City
Kampala
Country
Uganda
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emmy H Okello
Phone
+256775522284
Email
emmyoks@gmail.com

12. IPD Sharing Statement

Learn more about this trial

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

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