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.
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 3
Contactos e Locais
Contato de estudo
- Nome: Anubha Agarwal, MD MSc
- Número de telefone: 314-362-1291
- E-mail: anubha@wustl.edu
Estude backup de contato
- Nome: Adam Hively, MPH
- E-mail: adamh@wustl.edu
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Solteiro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Braço de intervenção em estudo
Os participantes do grupo de intervenção receberão o HFREF Polypill pelo estudo.
|
A insuficiência cardíaca com a fração de ejeção reduzida (HFREF) Polypill incluirá 4 medicamentos recomendados de diretrizes usados para tratar pacientes com HFREF. A dose de iniciação e titulação estará a critério do investigador. HFREF Polypill Resistência 1: bisoprolol 2,5 mg + losartan 25 mg + eplerenona 25 mg + dapagliflozina 10 mg; HFREF Polypill Força 2: bisoprolol 5 mg + losartan 50 mg + eplerenona 25 mg + dapagliflozina 10 mg; HFREF Polypill Força 3: Bisoprolol 10 mg + Losartan 100 + eplerenona 50 mg + dapagliflozina 10 mg |
|
Comparador Ativo: Control arm
Participants in the comparator control arm will receive usual care, as per their physician's discretion.
|
Os participantes do grupo de controle do comparador receberão atendimento usual por seus profissionais de saúde.
Os provedores serão incentivados a tratar todos os participantes de acordo com as diretrizes de prática clínica internacional e local.
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations
Prazo: 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.
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Rate of cardiovascular disease mortality
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 6 and 12 months
|
Dose optimization assessed as proportion achieving final/target doses
|
6 and 12 months
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Serious adverse events or sudden unexpected serious adverse reaction
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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.
|
Colaboradores e Investigadores
Publicações e links úteis
Links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- 202605087
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