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
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Anubha Agarwal, MD MSc
- 電話番号：314-362-1291
- メール：anubha@wustl.edu
研究連絡先のバックアップ
- 名前：Adam Hively, MPH
- メール：adamh@wustl.edu
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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 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 medically 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 2 months.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：独身
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：介入群を研究します
介入グループの参加者には、研究によりHFREFポリーピルが提供されます。
|
排出率が低下した心不全（HFREF）ポリーピルには、HFREF患者の治療に使用される4つのガイドライン推奨薬が含まれます。 開始と滴定の用量は、調査員の裁量で行われます。 HFREFポリーピル強度1：ビソプロロール2.5 mg +ロサルタン25 mg +エプレロン25 mg +ダパグリフロジン10 mg; HFREFポリーピル強度2：ビソプロロール5 mg +ロサルタン50 mg +エプレノン25 mg +ダパグリフロジン10 mg; HFREFポリーピル強度3：ビソプロロール10 mg +ロサルタン100 +エプレノン50 mg +ダパグリフロジン10 mg |
|
アクティブコンパレータ：Control arm
Participants in the comparator control arm will receive usual care, as per their physician's discretion.
|
Comparator Control Groupの参加者は、医療提供者から通常のケアを受けます。
プロバイダーは、国際および地域の臨床診療ガイドラインに従ってすべての参加者を治療することをお勧めします。
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations
時間枠：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.
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Rate of cardiovascular disease mortality
時間枠：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
時間枠：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
時間枠：1 month, 3 months, 6 months, 9 months, 12 months, through study completion, an average of 18 months.
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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
時間枠：Baseline, 12 months
|
How much the heart's pumping ability changes over one year, measured using a heart ultrasound test (echocardiogram).
|
Baseline, 12 months
|
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Natriuretic peptide levels change
時間枠：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.
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Baseline, 12 months
|
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Change in overall and domain specific health-related quality of life
時間枠：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.
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Baseline, 12 months
|
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Physician-reported New York Heart Association class change
時間枠：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
|
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Adherence to guideline-directed medical therapy
時間枠：Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
|
Medication adherence assessed by pill count.
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Baseline, 1 month, 3 months, 6 months, 9 months, 12 months
|
|
Adherence to Guideline-Directed Medical Therapy
時間枠：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
|
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Persistence to Guideline-Directed Medical Therapy
時間枠：Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
|
Medication persistence assessed as continuation of assigned therapy after initiation
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Baseline, 1 month, 3 month, 6 month, 9 month, 12 month
|
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Optimization of Guideline-Directed Medical Therapy
時間枠：6 and 12 months
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Dose optimization assessed as proportion achieving final/target doses
|
6 and 12 months
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Serious adverse events or sudden unexpected serious adverse reaction
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
|
協力者と研究者
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
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