HFrEF Polypill in Sri Lanka RCT
Trial statusNot yet recruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorWashington University School of Medicine
About this trial
Primary Outcome:
Composite of cardiovascular death or recurrent heart failure hospitalization over study duration
Secondary Outcomes:
Cardiovascular death over study duration Recurrent heart failure hospitalizations over study duration All-cause mortality over study duration Change in left ventricular ejection fraction from baseline to 12 months by echocardiogram.
Change in natriuretic peptide levels from baseline to 12 months. Change in health-related quality of life from baseline to 12 months using the Kansas City Cardiomyopathy Questionnaire.
Change in New York Heart Association functional class from baseline to 12 months.
Adherence to heart failure medications assessed by pill count and questionnaire, medication persistence assessed as continuation of assigned therapy after initiation, and dose optimization assessed as proportion achieving final/target doses over study duration
Safety Outcomes:
Proportion of participants with serious adverse events or sudden unexpected serious adverse reaction over study duration Proportion with adverse events of special interest (symptomatic hypotension, diabetic ketoacidosis, severe hypoglycemia, lower limb amputation, hyperkalemia, or worsening kidney function) over study duration Proportion of participants who stop study drug because of adverse events over study duration Change in serum potassium over study duration Change in serum creatinine over study duration
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 a minimum of 12-months 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adults (≥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
Disqualifiers
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)
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Comparator Arm
Other interventionParticipants 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.
HFrEF Polypill
DrugThe 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
Treatment groups
1,656 Participants
are divided into 2 treatment groupsGroup A: Control armActive comparator 1 intervention
Group B: Study Intervention armExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations
Cardiovascular disease mortality is defined as death due to acute myocardial infarction, worsening heart failure, stroke, sudden cardiac death, arrhythmia, pulmonary embolism, cardiovascular procedures, vascular causes, or any death of unknown cause unless a non-cardiovascular etiology is clearly established. Recurrent HF hospitalizations is defined as any hospitalization in which the primary cause is worsening heart failure, accompanied by objective evidence of decompensation and requiring initiation or intensification of HF-specific therapy, occurring after a documented period of clinical stability of at least 12 hours since the prior HF event. Adjudicated by the blinded Outcome Adjudication Committee.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.Secondary outcomes
1
Rate of cardiovascular disease mortality
Cardiovascular disease mortality is defined as death due to acute myocardial infarction, worsening heart failure, stroke, sudden cardiac death, arrhythmia, pulmonary embolism, cardiovascular procedures, vascular causes, or any death of unknown cause unless a non-cardiovascular etiology is clearly established. Adjudicated by the blinded Outcome Adjudication Committee.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.2
Rate of recurrent heart failure hospitalizations
Recurrent HF hospitalizations is defined as any hospitalization in which the primary cause is worsening heart failure, accompanied by objective evidence of decompensation and requiring initiation or intensification of HF-specific therapy, occurring after a documented period of clinical stability of at least 12 hours since the prior HF event. Adjudicated by the blinded Outcome Adjudication Committee.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.3
Rate of all-cause mortality
All-cause mortality is defined as death due to any cause.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.4
Change in left ventricular ejection fraction
How much the heart's pumping ability changes over one year, measured using a heart ultrasound test (echocardiogram).
Time frame
Baseline, 12 monthsOther outcomes
1
Serious adverse events or sudden unexpected serious adverse reaction
Proportion of participants with serious adverse events or sudden unexpected serious adverse reaction according to the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines (ICH E6 \[R3\]) over the study duration.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.2
Adverse Events of Special Interest
Adverse events of special interest defined as: a) symptomatic hypotension defined as systolic blood pressure \< 90 mmHg and associated symptoms of light-headedness, dizziness, or pre-syncope, b) diabetic ketoacidosis, c) severe hypoglycemic event, d) lower limb amputation, e) hyperkalemia defined as serum potassium greater than or equal to 5.5 mEq/L, and f) worsening renal function defined as ≥50% increase in serum creatinine or at a lower threshold per physician judgement.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.3
Adverse events leading to study drug discontinuation
Number of participants who stop the study medication because of side effects during the study.
Time frame
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.4
Serum potassium (mEq/L) change
Mean (average) change in serum potassium levels over study duration
Time frame
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.Locations
Sponsors and contacts
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Washington University School of Medicine
Lead sponsor
The George Institute
Collaborator
Centre for Chronic Disease Control, India
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
RemediumOne
Collaborator
Source ClinicalTrials.gov
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