Denne side blev automatisk oversat, og nøjagtigheden af ​​oversættelsen er ikke garanteret. Der henvises til engelsk version for en kildetekst.

HFrEF Polypill in Sri Lanka RCT

14. maj 2026 opdateret af: 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.

Studieoversigt

Status

Ikke rekrutterer endnu

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

1656

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

  • Navn: Anubha Agarwal, MD MSc
  • Telefonnummer: 314-362-1291
  • E-mail: anubha@wustl.edu

Undersøgelse Kontakt Backup

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Enkelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Undersøg interventionsarm
Deltagere i interventionsgruppen får HFREF -polypillen ved undersøgelsen.
Medicin: HFREF -polypill

Hjertesvigt med reduceret ejektionsfraktion (HFREF) polypill vil omfatte 4 retningslinje, der er anbefalet medicin, der blev anvendt til behandling af HFREF -patienter. Dosis af initiering og titrering vil være efter efterforskerens skøn.

HFREF Polypill Strength 1: Bisoprolol 2,5 mg + losartan 25 mg + eplerenon 25 mg + dapagliflozin 10 mg; Hfref Polypill Strength 2: Bisoprolol 5 mg + losartan 50 mg + eplerenon 25 mg + dapagliflozin 10 mg; Hfref Polypill Strength 3: Bisoprolol 10 mg + losartan 100 + eplerenon 50 mg + dapagliflozin 10 mg
Aktiv komparator: Control arm
Participants in the comparator control arm will receive usual care, as per their physician's discretion.
Andet: Komparatorarm
Deltagere i Comparator Control Group vil modtage sædvanlig pleje af deres sundhedsudbydere. Udbydere opfordres til at behandle alle deltagere i henhold til internationale og lokale retningslinjer for klinisk praksis.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Composite rate of cardiovascular disease mortality and recurrent HF hospitalizations
Tidsramme: 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.

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Rate of cardiovascular disease mortality
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 6 and 12 months
Dose optimization assessed as proportion achieving final/target doses
6 and 12 months

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Serious adverse events or sudden unexpected serious adverse reaction
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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.

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Washington University School of Medicine

Samarbejdspartnere

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

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Anslået)

1. juni 2026

Primær færdiggørelse (Anslået)

1. december 2028

Studieafslutning (Anslået)

1. marts 2029

Datoer for studieregistrering

Først indsendt

11. februar 2026

Først indsendt, der opfyldte QC-kriterier

1. maj 2026

Først opslået (Faktiske)

6. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

18. maj 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

14. maj 2026

Sidst verificeret

1. maj 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 202605087

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

IPD-planbeskrivelse

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.

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ingen

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Komparatorarm

Søg i lignende forsøg

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

CROs by country

CROs in Russia

Betingelser

Sjældne sygdomme

Narkotikainterventioner

Kosttilskud

Sponsor / samarbejdspartnere

Placeringer

Abonner