Home » Trials » SLCTR/2024/003


Heart Failure with Reduced Ejection Fraction Polypill Implementation Strategy in South Asia: A Pilot Randomized Trial

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SLCTR Registration Number

SLCTR/2024/003


Date of Registration

11 Feb 2024

The date of last modification

Feb 14, 2024



Application Summary


Scientific Title of Trial

Heart Failure with Reduced Ejection Fraction Polypill Implementation Strategy in South Asia: A Pilot Randomized Trial


Public Title of Trial

A Pilot Randomized Trial Evaluating the Feasibility and Safety of a Polypill Implementation Strategy in Patients with Heart Failure with Reduced Ejection Fraction in South Asia


Disease or Health Condition(s) Studied

Heart failure with reduced ejection fraction


Scientific Acronym

None


Public Acronym

HFrEF polypill trial


Brief title

None


Universal Trial Number

U1111-1298-9994


Any other number(s) assigned to the trial and issuing authority

P/111/08/2023; Faculty of Medicine, University of Kelaniya


Trial Details


What is the research question being addressed?

Is the study design feasible to assess the efficacy, safety and enhance adherence to guideline-directed medical therapy (GDMT) of the HFrEF polypill strategy, compared to standard of care for HFrEF patients in South Asia?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Masking not used


Control

Standard therapy/practice


Assignment

Parallel


Purpose

Treatment


Study Phase

Not Applicable


Intervention(s) planned

Study sites: The National Hospital of Sri Lanka and Colombo South Teaching Hospital.

Intervention: The study intervention will be a HFrEF polypill consisting of a Beta Blocker (BB), an Angiotensin receptor blocker (ARB), an mineralocorticoid receptor antagonist (MRA), and a Sodium-glucose cotransporter-2 inhibitor (SGLT2i) manufactured using the over-encapsulation method. The HFrEF polypill will be manufactured in 3 strengths to facilitate initiation with half-dose to prioritize clinical tolerability and laboratory safety and titration to a full-dose and double-dose HFrEF polypill. The dose of initiation and titration will be at the investigator’s discretion based on the clinical history and laboratory assessments.

Proposed HFrEF polypill combination, initiation, and titration schedule:
HFrEF polypill 1 (half-dose): bisoprolol 1.25 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg HFrEF polypill 2 (Full-dose): bisoprolol 5 mg + losartan 100 mg + eplerenone 25 mg + dapagliflozin 10 mg
HFrEF polypill 3 (Double-dose): bisoprolol 10 mg + losartan 150 + eplerenone 50 mg + dapagliflozin 10 mg

Randomization will be done through a randomization list for equal allocation (1:1) to intervention arm and comparator arm through the electronic data capturing system REDCap. Participants in the control arm will receive the standard of care by their healthcare providers. Healthcare providers will be encouraged to treat all participants according to international and local clinical practice guidelines. Participants in the intervention arm will be provided the HFrEF polypill by the study. One week after starting study medication, participants’ clinical symptoms, vital signs, medication adherence, laboratory measures, and need for medication adjustment/up-titration will be evaluated.

Four weeks after starting study medication, participants’ clinical symptoms, vital signs, laboratory measures, health related quality of life and need for medication adjustment (including transitioning back to original HFrEF outpatient medication regimen) will be evaluated.


Inclusion criteria

  1. Adults [>=18 years old)
  2. 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%)
  3. New York Heart Association Class II, III, or IV symptoms

Exclusion criteria

  1. Known contraindication to any of the HFrEF polypill components (e.g., advanced renal disease, bradycardia, allergy, amongst others).
  2. Significant renal impairment (estimated glomerular filtration rate <30 mL/min/1.73 m
  3. Raised serum potassium >5 mEq/L.
  4. Symptomatic hypotension or systolic BP <100 mmHg as per the average of last 2 of the measurements at visit 1.
  5. Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
  6. Myocardial infarction, unstable angina, stroke or transient ischemic attack (TIA) within 12 weeks prior to enrollment.
  7. 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).
  8. 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.
  9. 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.
  10. Participant’s responsible physician believes it is not appropriate for participant to participate in the study.
  11. Inability or unwillingness to provide written informed consent.
  12. Involvement in the planning and/or conduct of the study.
  13. Unable to complete study procedures and/or plan to move out of the study site area in the next 2 months.


Primary outcome(s)

1.

1.Feasibility of recruitment and adherence to study protocols based on completion of Recruitment of up to 80 participants at a rate of 4 participants per week.

[

At end of participant recruitment for the study

]
2.

2.Feasibility of recruitment and adherence to study protocols based on completion of study related procedures (screening, randomization, study drug allocation, follow-up procedures, retention, and outpatient transition)

[

Week 4

]
3.

3.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) measured by pill count and self-report using structured questionnaire [in-house]

[

Week 4

]

Secondary outcome(s)

1.

Proportion of participants with any serious adverse events (SAEs) according to the Good Clinical Practice (GCP) definition

[

Week 1, Week 4

]
2.

Proportion of participants with adverse events of special interest (AESIs) which are hyperkalemia, worsening renal function, and hypotension.

[

Week 1, Week 4

]
3.

Proportion of withdrawals due to adverse events

[

Week 4

]
4.

Mean change (from baseline) in continuous serum potassium (mEq/L), controlling for baseline value

[

Baseline, Week 1, Week 4

]
5.

Mean change (from baseline) in continuous serum creatinine (mg/dL), controlling for baseline value

[

Baseline, Week 1, Week 4

]
6.

Change in B-type natriuretic peptide (BNP)

[

Baseline, Week 4

]
7.

Change in physician reported New York Heart Association (NYHA) functional class

[

Baseline, Week 1, Week 4

]
8.

Change in health-related quality of life

[

Baseline, Week 4

]
9.

Rate of HF hospitalization

[

Baseline, Week 1, Week 4

]
10.

Rate of cardiovascular disease mortality

[

Baseline, Week 1, Week 4

]

Target number/sample size

40 (20 in each arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2024-04-01


Anticipated end date

2024-07-01


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

Washington University in St. Louis 1 Brookings Drive, St. Louis, MO 63130 United States


Regulatory approvals

Approved



State of Ethics Review Approval


Status

Approved


Date of Approval

2023-09-29


Approval number

P/111/08/2023


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address:P.O Box 6, Thalagolla Road, Ragama, Sri Lanka
Telephone:+94 11 2961267
Email: ercmed@kln.ac.lk

Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr. Gotabhaya Ranasinghe
General and Interventional Cardiologist
Institute of Cardiology, National Hospital of Sri Lanka, Colombo 10
+94 112 691 111
+94 77 731 9143

gotabhayar@gmail.com

Contact Person for Public Queries

Dr. Gotabhaya Ranasinghe
General and Interventional Cardiologist
Institute of Cardiology, National Hospital of Sri Lanka, Colombo 10
+94 112 691 111


gotabhayar@gmail.com


Primary study sponsor/organization

Washington University in St. Louis

1 Brookings Drive, St. Louis, MO 63130 United States



https://wustl.edu.com

Secondary study sponsor (If any)







Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?

No


IPD sharing plan description


Study protocol available

No


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results