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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
The heart failure with reduced ejection fraction (HFrEF) polypill will include 4 guideline recommended medications used to treat HFrEF patients. The dose of initiation and titration will be at the investigator's discretion. HFrEF polypill strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg; HFrEF polypill strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg; HFrEF polypill strength 3: bisoprolol 10 mg + losartan 100 + eplerenone 50 mg + dapagliflozin 10 mg
Participants in the comparator control group will receive usual care by their healthcare providers. Providers will be encouraged to treat all participants according to international and local clinical practice guidelines.
National Hospital of Sri Lanka
Colombo, Sri Lanka
Colombo South Teaching Hospital
Colombo, Sri Lanka
Feasibility of recruitment
Feasibility of recruitment based on completion of the following: recruitment of up to 40 participants at a rate of 4 participants per week.
Time frame: 0 - 10 weeks, start of enrollment to completion of participant enrollment
Adherence to study procedures
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).
Time frame: 0 - 14 weeks, baseline to study end
Adherence to overall and individual components of GDMT
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).
Time frame: 4 weeks
Withdrawals due to Adverse Events
Proportion of withdrawals due to adverse events.
Time frame: From enrollment to the end of treatment at 4 weeks
Serious Adverse Events
Proportion of participants with any serious adverse events (SAEs) according to the Good Clinical Practice (GCP) definition.
Time frame: From enrollment to the end of treatment at 4 weeks
Adverse Events of Special Interest
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)
Time frame: From enrollment to the end of treatment at 4 weeks
Mean Change in Serum Potassium
Mean change (from baseline) in continuous serum potassium, controlling for baseline value.
Time frame: 4 weeks
Change in Serum Creatinine
Mean change (from baseline) in serum creatinine, controlling for baseline value.
Time frame: 4 weeks
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