Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy in Sri Lanka

Phase 1

Completed

• Conditions: Heart Failure With Reduced Ejection Fraction
• Interventions: Other: Comparator Arm; Drug: HFrEF Polypill

• Registration Number: NCT06831864
• Lead Sponsor: Washington University School of Medicine

Brief Summary

The primary objective of this trial is to see if the research team can successfully recruit participants and carry out study related procedures in Sri Lanka. This will help the research team plan and execute a future large-scale trial in Sri Lanka.

The secondary objective is to assess whether a polypill for patients with heart failure with reduced ejection fraction (a type of heart condition) may help patients adhere to medications without an increase in serious adverse events.

An exploratory objective is to understand the process of implementation.

Participants will be randomly assigned to one of two groups, intervention or usual care. The intervention group will be given four guideline-recommended medications for heart failure with reduced ejection fraction, combined in one over-encapsulated pill, with three dose strength options (at the discretion of their treating physician). Both groups will be observed over 4-weeks of follow-up to assess their medication adherence, clinical symptoms, laboratory measures, health related quality of life, and need for medication adjustment amongst other measures.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-10
• Study First Submitted QC: 2025-02-11
• Study Start: 2025-02-15
• Study First Posted: 2025-02-18
• Status Verified: 2025-05
• Primary Completion: 2025-05-05
• Study Completion: 2025-05-05
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Adults (age ≥18 years old)
• Diagnosis of heart failure with reduced ejection fraction (HFrEF) including clinical symptoms or clinical signs or natriuretic peptide elevation AND echocardiographic or other evidence of reduced ejection fraction (EF 40%)
• New York Heart Association Class II, III, or IV symptoms

Exclusion Criteria

• Known contraindication to any of the HFrEF polypill components (e.g., advanced renal disease, bradycardia, allergy, amongst others).
• Significant renal impairment (estimated glomerular filtration rate <=30 mL/min/1.73 m2 or creatinine clearance <=30mL/min).
• Raised serum potassium >5 mEq/L.
• Symptomatic hypotension or systolic BP <100 mmHg as per the average of last 2 of the 3 measurements at visit 1.
• Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
• Cardiogenic shock and/or current use of inotropes.
• Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.
• Women who are pregnant, breastfeeding or of childbearing potential and are not using and do not plan to continue using medically acceptable form of contraception throughout the study (pharmacological or barrier methods).
• Concomitant illness, physical impairment or mental condition which in the opinion of the study team / primary physician could interfere with the conduct of the study including outcome assessment.
• Participation in a concurrent interventional medical investigation or pharmacologic clinical trial. Patients in observational, natural history or epidemiological studies not involving an intervention are eligible.
• Participant's responsible physician believes it is not appropriate for participant to participate in the study.
• Inability or unwillingness to provide written informed consent.
• Involvement in the planning and/or conduct of the study.
• Unable to complete study procedures and/or plan to move out of the study site area in the next 2 months.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Comparator (control) arm	Comparator Arm	Participants in the comparator control arm will receive usual care, as per their physician's discretion.
Study Intervention arm	HFrEF Polypill	Participants in the intervention group will be provided the HFrEF polypill by the study.

Primary Outcome Measures

Name	Time	Method
Adherence to study procedures	0 - 14 weeks, baseline to study end	Adherence to study procedures based on completion of the following: completion of study-related procedures (screening, randomization, study drug allocation, follow-up procedures, retention, and outpatient transition).
Feasibility of recruitment	0 - 10 weeks, start of enrollment to completion of participant enrollment	Feasibility of recruitment based on completion of the following: recruitment of up to 40 participants at a rate of 4 participants per week.

Secondary Outcome Measures

Name	Time	Method
Adherence to overall and individual components of GDMT	4 weeks	The secondary outcome is the proportion of individuals with adherence to overall and individual components of GDMT (ACE-I or ARB or ARNi, BB, MRA, and SGLT2i use at any dose in the absence of contraindications) at 4 weeks measured by 1) pill count, and 2) the self-report tool Medication Adherence Report Scale (MARS-5).
Serious Adverse Events	From enrollment to the end of treatment at 4 weeks	Proportion of participants with any serious adverse events (SAEs) according to the Good Clinical Practice (GCP) definition.
Mean Change in Serum Potassium	4 weeks	Mean change (from baseline) in continuous serum potassium, controlling for baseline value.
Withdrawals due to Adverse Events	From enrollment to the end of treatment at 4 weeks	Proportion of withdrawals due to adverse events.
Adverse Events of Special Interest	From enrollment to the end of treatment at 4 weeks	Proportion of participants with adverse events of special interest (diabetic ketoacidosis, volume depletion \[hypotension, syncope, orthostatic hypotension or dehydration all defined clinically\], severe hypoglycemic event, lower limb amputation, hyperkalemia, worsening renal function)
Change in Serum Creatinine	4 weeks	Mean change (from baseline) in serum creatinine, controlling for baseline value.

Trial Locations

Locations (2)

Colombo South Teaching Hospital; 🇱🇰 Colombo, Sri Lanka

National Hospital of Sri Lanka; 🇱🇰 Colombo 10, Sri Lanka