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HFrEF Polypill in Sri Lanka RCT

14. května 2026 aktualizováno: Washington University School of Medicine

Heart Failure With Reduced Ejection Fraction Polypill in Sri Lanka: A Multi-Center Type I Hybrid Randomized Controlled 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.

Přehled studie

Postavení

Zatím nenabíráme

Podmínky

Intervence / Léčba

Detailní popis

The study intervention will be a heart failure with reduced ejection fraction (HFrEF) polypill consisting of bisoprolol (beta-blocker), losartan (ARB), eplerenone (MRA), and dapagliflozin (SGLT2i) manufactured using the over-encapsulation method and will undergo extensive stability testing to ensure quality. There will be 3 strengths of the HFrEF polypill available to facilitate initiation with low dose to prioritize clinical tolerability and laboratory safety and titration to higher doses of the HFrEF polypill. The dose of initiation and titration will be at the investigator's discretion. The HFrEF polypill will be delivered by licensed physicians responsible for managing heart failure at participating sites. Eligible providers must have formal medical qualifications in Sri Lanka and be actively involved in the care of patients with HFrEF. This includes cardiologists, internists, or general practitioners with experience in heart failure management. All participating physicians will receive standardized training on the study protocol including titration protocol, HFrEF polypill composition, and guidance for patient counseling prior to trial initiation to ensure consistent and accurate delivery of the intervention. Participants receiving the HFrEF polypill will also receive a "HFrEF polypill card" that delineates the drugs and doses included in the HFrEF polypill combination and contact information for the local study team in case of hospitalization at another facility.

HFrEF polypill combinations by strength:

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 from their healthcare providers. Providers will be encouraged to treat all participants according to international and local clinical practice guidelines. Participants in the intervention group will be provided with the HFrEF polypill by the study, and participants in the control group will be provided HFrEF medications through the pharmacy at the public hospital site(s) in Sri Lanka where they are generally free of cost.

Typ studie

Intervenční

Zápis (Odhadovaný)

1656

Fáze

  • Fáze 3

Kontakty a umístění

Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.

Studijní kontakt

  • Jméno: Anubha Agarwal, MD MSc
  • Telefonní číslo: 314-362-1291
  • E-mail: anubha@wustl.edu

Studijní záloha kontaktů

Kritéria účasti

Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.

Kritéria způsobilosti

Věk způsobilý ke studiu

  • Dospělý
  • Starší dospělý

Přijímá zdravé dobrovolníky

Ne

Popis

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 m2)
  3. Raised serum potassium >5 mEq/L.
  4. Symptomatic hypotension or systolic BP <100 mmHg as per the average of last 2 of the 3 measurements at visit 1.
  5. Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
  6. History of type 1 diabetes mellitus.
  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.

Studijní plán

Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.

Jak je studie koncipována?

Detaily designu

  • Primární účel: Léčba
  • Přidělení: Randomizované
  • Intervenční model: Paralelní přiřazení
  • Maskování: Singl

Zbraně a zásahy

Skupina účastníků / Arm
Intervence / Léčba
Experimentální: Studijní intervenční rameno
Účastníci intervenční skupiny budou studie poskytnuty HFREF polypill.
Lék: HFREF Polypill

Srdeční selhání se sníženou ejekční frakcí (HFREF) polypill bude zahrnovat 4 pokyny doporučené léky používané k léčbě pacientů s HFREF. Dávka zahájení a titrace bude na uvážení vyšetřovatele.

Síla polypilu HFREF 1: bisoprolol 2,5 mg + losartan 25 mg + eplerenon 25 mg + dapagliflozin 10 mg; Síla polypilu HFREF 2: bisoprolol 5 mg + losartan 50 mg + eplerenon 25 mg + dapagliflozin 10 mg; Síla polypilu HFREF 3: Bisoprolol 10 mg + losartan 100 + eplerenon 50 mg + dapagliflozin 10 mg
Aktivní komparátor: Control arm
Participants in the comparator control arm will receive usual care, as per their physician's discretion.
Jiný: Srovnávací rameno
Účastníci kontrolní skupiny komparátorů dostanou jejich poskytovatelé zdravotní péče obvyklou péči. Poskytovatelé budou povzbuzováni, aby léčili všechny účastníky podle pokynů mezinárodní a místní klinické praxe.

Co je měření studie?

Primární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

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.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

Sekundární výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Rate of cardiovascular disease mortality
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

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.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Rate of recurrent heart failure hospitalizations
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

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.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Rate of all-cause mortality
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
All-cause mortality is defined as death due to any cause.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Change in left ventricular ejection fraction
Časové okno: Baseline, 12 months
How much the heart's pumping ability changes over one year, measured using a heart ultrasound test (echocardiogram).
Baseline, 12 months
Natriuretic peptide levels change
Časové okno: Baseline, 12 months
Change in a blood test that reflects heart stress using a validated commercially available immunoassay (i.e., BNP) from baseline to 12 months.
Baseline, 12 months
Change in overall and domain specific health-related quality of life
Časové okno: Baseline, 12 months
Health-related quality of life (HRQoL) will be assessed using a validated, translated Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23). The KCCQ-23 measures overall and domain-specific HRQoL, including physical limitation, symptom frequency and impact, quality of life, and social limitation. Scores are transformed to a 0-100 scale, with higher scores indicating better health status; change from baseline to 12 months will be analyzed for overall and domain-specific scores. Overall summary score will be used as a secondary outcome. Domain-specific scores will be considered exploratory.
Baseline, 12 months
Physician-reported New York Heart Association class change
Časové okno: Baseline, 12 months
Change in how severe heart failure symptoms are over 12 months, as rated by the doctor (New York Heart Association class).
Baseline, 12 months
Adherence to guideline-directed medical therapy
Časové okno: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
Medication adherence assessed by pill count.
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
Adherence to Guideline-Directed Medical Therapy
Časové okno: Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
Medication adherence assessed by MARS-5 questionnaire
Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
Persistence to Guideline-Directed Medical Therapy
Časové okno: Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
Medication persistence assessed as continuation of assigned therapy after initiation
Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
Optimization of Guideline-Directed Medical Therapy
Časové okno: 6 and 12 months
Dose optimization assessed as proportion achieving final/target doses
6 and 12 months

Další výstupní opatření

Měření výsledku
Popis opatření
Časové okno
Serious adverse events or sudden unexpected serious adverse reaction
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
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.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Adverse Events of Special Interest
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
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.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Adverse events leading to study drug discontinuation
Časové okno: 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Number of participants who stop the study medication because of side effects during the study.
1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Serum potassium (mEq/L) change
Časové okno: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Mean (average) change in serum potassium levels over study duration
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Serum creatinine (mg/dL) change
Časové okno: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
Mean (average) change in a serum creatinine over study duration
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.

Spolupracovníci a vyšetřovatelé

Zde najdete lidi a organizace zapojené do této studie.

Sponzor

Washington University School of Medicine

Spolupracovníci

National Heart, Lung, and Blood Institute (NHLBI)
Centre for Chronic Disease Control, India
The George Institute
RemediumOne

Publikace a užitečné odkazy

Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.

Užitečné odkazy

Termíny studijních záznamů

Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.

Hlavní termíny studia

Začátek studia (Odhadovaný)

1. června 2026

Primární dokončení (Odhadovaný)

1. prosince 2028

Dokončení studie (Odhadovaný)

1. března 2029

Termíny zápisu do studia

První předloženo

11. února 2026

První předloženo, které splnilo kritéria kontroly kvality

1. května 2026

První zveřejněno (Aktuální)

6. května 2026

Aktualizace studijních záznamů

Poslední zveřejněná aktualizace (Aktuální)

18. května 2026

Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality

14. května 2026

Naposledy ověřeno

1. května 2026

Více informací

Termíny související s touto studií

Klíčová slova

Další relevantní podmínky MeSH

Další identifikační čísla studie

  • 202605087

Plán pro data jednotlivých účastníků (IPD)

Plánujete sdílet data jednotlivých účastníků (IPD)?

NE

Popis plánu IPD

When the study is over, research findings will be available at www.ClinicalTrials.gov and Sri Lanka Clinical Trials Registry. Laboratory results will be shared with participants and their health care providers. The research findings will also be published in the form of research articles or presented at scientific meetings.

Informace o lécích a zařízeních, studijní dokumenty

Studuje lékový produkt regulovaný americkým FDA

Ne

Studuje produkt zařízení regulovaný americkým úřadem FDA

Ne

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