Date

2025-01-23

Protocol

Protocol changed

Item Changed

Intervention(s) planned

Previous Version

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.

Next Version

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: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg HFrEF polypill 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg HFrEF polypill 3: bisoprolol 10 mg + losartan 100 mg + 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.