HFrEF Polypill in Sri Lanka RCT
Heart Failure With Reduced Ejection Fraction Polypill in Sri Lanka: A Multi-Center Type I Hybrid Randomized Controlled Trial
The aim of this study is to evaluate, in adults with HFrEF in Sri Lanka, the effects of an HFrEF polypill implementation strategy on the composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations, compared with usual care over a minimum of 12-months of follow-up.
Primary outcome of the study:
1) Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration
Secondary outcomes of the study:
- Rate of cardiovascular disease mortality over study duration
- Rate of recurrent heart failure hospitalizations over the study duration
- Rate of all-cause mortality over the study duration
- Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
- Change in BNP levels at 12 months and end of study
- Change in overall and domain specific health-related quality of life at 12-months and end of study assessed by a translated validated version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-23)
- Change in physician-reported New York Heart Association class at 12-months and end of study
- Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire at baseline, 1-, 6-, 12-months, and end of study. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study.
Safety outcomes:
- Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
- Proportion of participants with adverse events of special interest over study duration
- Proportion of participants with adverse events leading to HF drug discontinuation over study duration
- Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)
- Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL)
Participants will be randomly assigned 1:1 stratified by sex and site to one of two groups, intervention (experimental arm) or usual care (control arm). 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. Both groups will be observed over a minimum of 12-months of follow-up to assess key outcomes.
Przegląd badań
Status
Status
Warunki
Warunki
Interwencja / Leczenie
Interwencja / Leczenie
Szczegółowy opis
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 studiów
Typ studiów
Zapisy (Szacowany)
Zapisy
Faza
Faza
- Faza 3
Kontakty i lokalizacje
Kontakt w sprawie studiów
Kontakt w sprawie studiów
- Nazwa: Anubha Agarwal, MD MSc
- Numer telefonu: +1 314-362-1291
- E-mail: anubha@wustl.edu
Kopia zapasowa kontaktu do badania
- Nazwa: Asita de Silva, MBBS DPhil FRCP
- Numer telefonu: +94 11 2961241
- E-mail: asita@kln.ac.lk
Lokalizacje studiów
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Central Province
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Kandy, Central Province, Sri Lanka, 20000
- Rekrutacyjny
- National Hospital Kandy
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Kontakt:
- Gnanamoorthy Mayurathan
- Numer telefonu: +94 812 222 261
- E-mail: gkmayurathan@yahoo.com
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Pod-śledczy:
- Zanoona Siddeek
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North Western Province
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Kurunegala, North Western Province, Sri Lanka, 60000
- Jeszcze nie rekrutacja
- Teaching Hospital Kurunegala
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Kontakt:
- Thusitha Wijethunga
- Numer telefonu: +94 372 222 261
- E-mail: tjwijethunga@gmail.com
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Pod-śledczy:
- Aruna Jayawarna
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Northern Province
-
Jaffna, Northern Province, Sri Lanka, 40000
- Rekrutacyjny
- Teaching Hospital Jaffna
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Kontakt:
- Poopalan Lakshman
- Numer telefonu: +94 212 223 348
- E-mail: drplcc7@gmail.com
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Pod-śledczy:
- Thepana Sasiharan
-
Pod-śledczy:
- Sebastian Heavenly
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Ratnapura
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Colombo, Ratnapura, Sri Lanka, 70000
- Jeszcze nie rekrutacja
- Rathnapura Teaching Hospital
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Kontakt:
- Chinthaka Hathlahawatta
- Numer telefonu: +94 718036938
- E-mail: chinthaka.hat@gmail.com
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Southern Province
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Galle, Southern Province, Sri Lanka, 80000
- Rekrutacyjny
- National Hospital Galle
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Kontakt:
- Sandamali Premaratne
- Numer telefonu: +94 912 232 267
- E-mail: sandamali.premaratne@gmail.com
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Pod-śledczy:
- Piumi Rajawardhana
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Pod-śledczy:
- T.G Sandamali
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Western Province
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Colombo, Western Province, Sri Lanka, 00100
- Jeszcze nie rekrutacja
- National Hospital of Sri Lanka
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Kontakt:
- Gamini Galappatthy
- Numer telefonu: +94 112 691 111
- E-mail: gamini_galappatthy@hotmail.com
-
Pod-śledczy:
- Chandrike Ponnamperuma
-
Pod-śledczy:
- Thisal Semina
-
Pod-śledczy:
- Tanya Pereira
-
Pod-śledczy:
- Neranja Weerakoon
-
Pod-śledczy:
- Chandana Wijesingha
-
Pod-śledczy:
- Bhathiya Ranasinghe
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Colombo, Western Province, Sri Lanka, 10290
- Jeszcze nie rekrutacja
- University Hospital - General Sir John Kotelawala Defence University
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Kontakt:
- Namal Wijesinghe
- Numer telefonu: +94 112044555
- E-mail: namalw@gmail.com
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Pod-śledczy:
- Subash Karunarathna
-
Pod-śledczy:
- Sandali Wijewardena
-
Pod-śledczy:
- Gishara Hemachandra
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Pod-śledczy:
- Sashini Amarasinghe
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Dehiwala, Western Province, Sri Lanka, 10350
- Rekrutacyjny
- Colombo South Teaching Hospital
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Kontakt:
- M. B. F. Rahuman
- Numer telefonu: +94 112 832 950
- E-mail: faslurcard@yahoo.com
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Pod-śledczy:
- Geethani Gunasekara
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Gampaha, Western Province, Sri Lanka, 11000
- Jeszcze nie rekrutacja
- Gampaha District General Hospital
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Kontakt:
- Suneth Karunarathne
- Numer telefonu: 94 332 222 261
- E-mail: suneth87@gmail.com
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Negombo, Western Province, Sri Lanka, 11500
- Jeszcze nie rekrutacja
- District General Hospital Negombo
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Kontakt:
- Ajith Wanniarachchi
- Numer telefonu: +94 312 222 261
- E-mail: ajithwap@gmail.com
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Pod-śledczy:
- Anusha de Silva
-
Ragama, Western Province, Sri Lanka, 11010
- Rekrutacyjny
- Colombo North Teaching Hospital
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Kontakt:
- Sanjeewa Rajapakse
- Numer telefonu: +94 11 2959261-4
- E-mail: sanjeewargs@yahoo.com
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Pod-śledczy:
- Thushari Gunawardana
-
Pod-śledczy:
- Sinthi Sivarajah
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Pod-śledczy:
- Anjalee Weerasuriya
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Kryteria uczestnictwa
Kryteria kwalifikacji
Kryteria kwalifikacji
Wiek uprawniający do nauki
- Dorosły
- Starszy dorosły
Akceptuje zdrowych ochotników
Opis
Inclusion Criteria:
- 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 left ventricular ejection fraction (EF ≤40%)
- New York Heart Association Class II, III, or IV symptoms
Exclusion Criteria:
- 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.
- Symptomatic bradycardia or second or third-degree heart block without a pacemaker on ECG review at visit 1.
- History of type 1 diabetes mellitus.
- Women who are pregnant, breastfeeding or of childbearing potential and are not using and do not plan to continue using a highly acceptable form of contraception throughout the study (pharmacological or barrier methods).
- 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.
- 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.
- Participant's responsible physician believes it is not appropriate for participant to participate in the study.
- Inability or unwillingness to provide written informed consent.
- Involvement in the planning and/or conduct of the study.
- Unable to complete study procedures and/or plan to move out of the study site area in the next 12 months.
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Randomizowane
- Model interwencyjny: Przydział równoległy
- Maskowanie: Pojedynczy
Liczba ramion
Broń i interwencje
Grupa uczestników / ArmGrupa uczestników / Arm |
Interwencja / LeczenieInterwencja / Leczenie |
|---|---|
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Aktywny komparator: Usual Care
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 will receive their HFrEF medications through the pharmacy at the sites, where guideline-directed medical therapy are dispensed without charge to participants when available on the public hospital formulary.
|
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 will receive their HFrEF medications through the pharmacy at the sites, where guideline-directed medical therapy are dispensed without charge to participants when available on the public hospital formulary.
|
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Eksperymentalny: HFrEF Polypill
The study intervention is a HFrEF polypill consisting of bisoprolol (beta-blocker), losartan (ARB), eplerenone (MRA), and dapagliflozin (SGLT2i) manufactured using the over-encapsulation method. There will be 3 strengths of the HFrEF polypill available: Strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 3: bisoprolol 10 mg + losartan 100 mg + eplerenone 50 mg + dapagliflozin 10 mg Every intervention participant will be established on the highest tolerated strength of the HFrEF polypill, with Strength 3 as the target dose. Following initiation at the strength matched to the participant's background guideline-directed medical therapy, the polypill strength will be advanced by one level at each scheduled study visit aligned with the initiation and titration protocol. |
The study intervention is a HFrEF polypill consisting of bisoprolol (beta-blocker), losartan (ARB), eplerenone (MRA), and dapagliflozin (SGLT2i) manufactured using the over-encapsulation method.
There will be 3 strengths of the HFrEF polypill available: Strength 1: bisoprolol 2.5 mg + losartan 25 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 2: bisoprolol 5 mg + losartan 50 mg + eplerenone 25 mg + dapagliflozin 10 mg Strength 3: bisoprolol 10 mg + losartan 100 mg + eplerenone 50 mg + dapagliflozin 10 mg.
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Co mierzy badanie?
Podstawowe miary wyniku
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month study visits, and every 3 months thereafter 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 or their complications, other vascular causes, or any death of unknown cause unless a non-cardiovascular etiology is clearly established. HF hospitalization is defined as any unplanned hospitalization for at least 24 hours, for which the primary cause is 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 month, 6 month, 9 month, 12 month study visits, and every 3 months thereafter through study completion, an average of 18 months.
|
Miary wyników drugorzędnych
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Rate of cardiovascular disease mortality over study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month study visits, and every 3 months thereafter, 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 or their complications, other 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 month, 6 month, 9 month, 12 month study visits, and every 3 months thereafter, through study completion, an average of 18 months.
|
|
Rate of recurrent heart failure hospitalizations over the study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
HF hospitalization is defined as any unplanned hospitalization for at least 24 hours, for which the primary cause is 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 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
|
Rate of all-cause mortality over the study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
All-cause mortality is defined as death due to any cause.
|
1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
|
Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
Ramy czasowe: Baseline, 12 months, and at study completion, an average of 18 months.
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
|
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Change in BNP levels at 12 months and end of study
Ramy czasowe: Baseline, 12 months, and at study completion, an average of 18 months.
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
|
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Change in overall and domain specific health-related quality of life at 12-months and end of study
Ramy czasowe: Baseline, 12 months, and at study completion, an average of 18 months.
|
Health-related quality of life (HRQoL) will be assessed by a translated validated Kansas City Cardiomyopathy Questionnaire-23 (KCCQ-23)
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
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Change in physician-reported New York Heart Association class at 12-months and end of study
Ramy czasowe: Baseline, 12 months, and at study completion, an average of 18 months.
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
|
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Adherence to guideline-directed medical therapy, persistence and dose optimization
Ramy czasowe: Baseline, 1, 6, 12 months, and at study completion, an average of 18 months
|
Adherence to guideline-directed medical therapy assessed by pill count and MARS-5 questionnaire. Persistence assessed as continuation of assigned therapy at each follow-up visit. Dose optimization assessed as proportion achieving target doses (Strength 3 of the polypill, or comparable individual GDMT doses in the comparator arm) at 6-, 12-months, and end of study. |
Baseline, 1, 6, 12 months, and at study completion, an average of 18 months
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Inne miary wyników
Inne miary wyników
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
Proportion of participants with serious adverse events according to Good Clinical Practice (GCP) guidelines (ICH E6 [R3]) over the study duration.
|
1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
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Proportion of participants with adverse events of special interest over study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
Adverse events of special interest:
|
1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
|
Proportion of participants with adverse events leading to HF drug discontinuation over study duration
Ramy czasowe: 1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
1 month, 3 month, 6 month, 9 month, 12 month visit, and thereafter every 3 months, through study completion, an average of 18 months.
|
|
|
Mean change from baseline to 12-months and end of study in serum potassium (mEq/L)
Ramy czasowe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.
|
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.
|
|
|
Mean change from baseline to 12-months and end of study in serum creatinine (mg/dL)
Ramy czasowe: Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.
|
Baseline, 1 month, 3 months, 6 months, 9 months, 12 months, and at study completion, an average of 18 months.
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Współpracownicy i badacze
Sponsor
Sponsor
Współpracownicy
Współpracownicy
Publikacje i pomocne linki
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Rozpoczęcie studiów
Zakończenie podstawowe (Szacowany)
Zakończenie podstawowe
Ukończenie studiów (Szacowany)
Ukończenie studiów
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Pierwszy wysłany
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia wysłana aktualizacja
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Słowa kluczowe
Dodatkowe istotne warunki MeSH
Inne numery identyfikacyjne badania
Inne numery identyfikacyjne badania
- 202605087
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu IPD
Ramy czasowe udostępniania IPD
Kryteria dostępu do udostępniania IPD
Typ informacji pomocniczych dotyczących udostępniania IPD
- PROTOKÓŁ BADANIA
- SOK ROŚLINNY
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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