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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 3단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: Anubha Agarwal, MD MSc
- 전화번호: +1 314-362-1291
- 이메일: anubha@wustl.edu
연구 연락처 백업
- 이름: Asita de Silva, MBBS DPhil FRCP
- 전화번호: +94 11 2961241
- 이메일: asita@kln.ac.lk
연구 장소
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Central Province
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Kandy, Central Province, 스리랑카, 20000
- 모병
- National Hospital Kandy
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연락하다:
- Gnanamoorthy Mayurathan
- 전화번호: +94 812 222 261
- 이메일: gkmayurathan@yahoo.com
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부수사관:
- Zanoona Siddeek
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North Western Province
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Kurunegala, North Western Province, 스리랑카, 60000
- 아직 모집하지 않음
- Teaching Hospital Kurunegala
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연락하다:
- Thusitha Wijethunga
- 전화번호: +94 372 222 261
- 이메일: tjwijethunga@gmail.com
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부수사관:
- Aruna Jayawarna
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Northern Province
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Jaffna, Northern Province, 스리랑카, 40000
- 모병
- Teaching Hospital Jaffna
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연락하다:
- Poopalan Lakshman
- 전화번호: +94 212 223 348
- 이메일: drplcc7@gmail.com
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부수사관:
- Thepana Sasiharan
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부수사관:
- Sebastian Heavenly
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Ratnapura
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Colombo, Ratnapura, 스리랑카, 70000
- 아직 모집하지 않음
- Rathnapura Teaching Hospital
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연락하다:
- Chinthaka Hathlahawatta
- 전화번호: +94 718036938
- 이메일: chinthaka.hat@gmail.com
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Southern Province
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Galle, Southern Province, 스리랑카, 80000
- 모병
- National Hospital Galle
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연락하다:
- Sandamali Premaratne
- 전화번호: +94 912 232 267
- 이메일: sandamali.premaratne@gmail.com
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부수사관:
- Piumi Rajawardhana
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부수사관:
- T.G Sandamali
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Western Province
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Colombo, Western Province, 스리랑카, 00100
- 아직 모집하지 않음
- National Hospital of Sri Lanka
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연락하다:
- Gamini Galappatthy
- 전화번호: +94 112 691 111
- 이메일: gamini_galappatthy@hotmail.com
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부수사관:
- Chandrike Ponnamperuma
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부수사관:
- Thisal Semina
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부수사관:
- Tanya Pereira
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부수사관:
- Neranja Weerakoon
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부수사관:
- Chandana Wijesingha
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부수사관:
- Bhathiya Ranasinghe
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Colombo, Western Province, 스리랑카, 10290
- 아직 모집하지 않음
- University Hospital - General Sir John Kotelawala Defence University
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연락하다:
- Namal Wijesinghe
- 전화번호: +94 112044555
- 이메일: namalw@gmail.com
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부수사관:
- Subash Karunarathna
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부수사관:
- Sandali Wijewardena
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부수사관:
- Gishara Hemachandra
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부수사관:
- Sashini Amarasinghe
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Dehiwala, Western Province, 스리랑카, 10350
- 모병
- Colombo South Teaching Hospital
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연락하다:
- M. B. F. Rahuman
- 전화번호: +94 112 832 950
- 이메일: faslurcard@yahoo.com
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부수사관:
- Geethani Gunasekara
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Gampaha, Western Province, 스리랑카, 11000
- 아직 모집하지 않음
- Gampaha District General Hospital
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연락하다:
- Suneth Karunarathne
- 전화번호: 94 332 222 261
- 이메일: suneth87@gmail.com
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Negombo, Western Province, 스리랑카, 11500
- 아직 모집하지 않음
- District General Hospital Negombo
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연락하다:
- Ajith Wanniarachchi
- 전화번호: +94 312 222 261
- 이메일: ajithwap@gmail.com
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부수사관:
- Anusha de Silva
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Ragama, Western Province, 스리랑카, 11010
- 모병
- Colombo North Teaching Hospital
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연락하다:
- Sanjeewa Rajapakse
- 전화번호: +94 11 2959261-4
- 이메일: sanjeewargs@yahoo.com
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부수사관:
- Thushari Gunawardana
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부수사관:
- Sinthi Sivarajah
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부수사관:
- Anjalee Weerasuriya
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
|---|---|
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활성 비교기: 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.
|
|
실험적: 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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연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Composite rate of cardiovascular disease mortality and recurrent heart failure hospitalizations over study duration
기간: 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.
|
2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Rate of cardiovascular disease mortality over study duration
기간: 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
기간: 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
기간: 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.
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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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Change in left ventricular ejection fraction at 12-months and end of study assessed by transthoracic echocardiogram
기간: Baseline, 12 months, and at study completion, an average of 18 months.
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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
기간: Baseline, 12 months, and at study completion, an average of 18 months.
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
|
|
Change in overall and domain specific health-related quality of life at 12-months and end of study
기간: 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.
|
|
Change in physician-reported New York Heart Association class at 12-months and end of study
기간: Baseline, 12 months, and at study completion, an average of 18 months.
|
Baseline, 12 months, and at study completion, an average of 18 months.
|
|
|
Adherence to guideline-directed medical therapy, persistence and dose optimization
기간: 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
|
기타 결과 측정
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Proportion of participants with serious adverse events according to Good Clinical Practice guidelines over study duration
기간: 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.
|
|
Proportion of participants with adverse events of special interest over study duration
기간: 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
기간: 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)
기간: 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)
기간: 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.
|
공동 작업자 및 조사자
협력자
협력자
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
기타 연구 ID 번호
- 202605087
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
IPD 공유 기간
IPD 공유 액세스 기준
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .