Heart Failure
Conditions
Brief summary
The Heart Failure Efficacy and Research Trial (HEART) Platform is a multicenter, randomized platform study designed to improve outcomes for patients with heart failure through the simultaneous and sequential evaluation of multiple interventions across the spectrum of heart failure.
Detailed description
The Heart Failure Efficacy and Research Trial (HEART) Platform is a multicenter, randomized platform clinical trial infrastructure designed to improve outcomes for adults with heart failure through the efficient and continuous evaluation of multiple interventions. The platform enables the simultaneous and sequential testing of therapies across the spectrum of heart failure, with the ability to add, modify, or close interventions ("domains") over time as evidence accumulates and new research questions emerge. HEART uses a master protocol framework with Domain-Specific Appendices (DSAs) that provide intervention-specific eligibility criteria, procedures, safety monitoring, and outcomes, while using shared platform-wide processes for governance, operations, data collection, and participant protections. This modular documentation structure allows platform updates and domain evolution without requiring complete revisions to all platform components, supporting long-term sustainability and reduced regulatory burden. Participants are enrolled into one of two mutually exclusive patient states at the time of randomization: (1) State 1: Worsening Heart Failure (WHF), which includes patients hospitalized or treated in the emergency department for acute heart failure requiring active management; and (2) State 2: Ambulatory Heart Failure, which includes stable outpatients with established heart failure receiving ongoing management and without recent heart failure hospitalization. Patient state determines eligibility for specific domains and supports state-specific analyses. Each HEART domain operates as a semi-autonomous trial within the broader infrastructure, with domain-specific scientific leadership and funding, while benefiting from shared core trial procedures. Domains may be conducted as vanguard/feasibility studies, Phase II trials, or Phase III trials, depending on the maturity of evidence and research objectives, and interventions may advance ("graduate") to later-phase evaluations within the platform. The default primary endpoint for Phase III trials within the platform is time to first event of death or cardiovascular hospitalization; however, specific primary outcomes are determined at the domain level to match the intervention and development phase. The HEART Platform incorporates formal governance and safety oversight, including a Platform Steering Committee and independent Data Safety Monitoring Board (DSMB), with standardized adverse event definitions and reporting procedures. The platform is conducted in accordance with Good Clinical Practice, the Declaration of Helsinki, and applicable ethical and regulatory requirements, with ethics approval obtained for the master protocol and each individual domain.
Interventions
OTHERDomain Intervention(s)
Participants randomized to the experimental arm will receive an intervention being evaluated within an eligible HEART Platform domain at the time of randomization. Domain interventions may change over time as domains are added, modified, or closed in accordance with the platform master protocol and domain-specific protocols.
OTHERControl / Standard of Care Comparator
Participants randomized to the comparator arm will receive concurrent control within eligible HEART Platform domains. Control may include placebo and/or standard-of-care management, depending on the domain-specific protocol.
Sponsors
University of Alberta
Canadian VIGOUR Centre
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Depends on domains
Intervention model description
This is a randomized platform trial in which multiple therapeutic domains (interventions) may be evaluated concurrently or sequentially over time within a shared master protocol. Participants are assigned to interventions within active domains based on eligibility at the time of randomization. Domains may be added, modified, or closed during the platform lifecycle.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
(HEART Platform) * Participants are eligible for inclusion if they meet all of the following: * Age ≥18 years (or legal age of majority in participant's country of residence). * Diagnosis of heart failure, and eligible to be classified into one of the HEART platform states at the time of randomization: * State 1: Worsening Heart Failure (WHF): currently hospitalized for acute decompensated heart failure or emergency department patients requiring intravenous therapy for heart failure; OR * State 2: Ambulatory Heart Failure: stable outpatients with established heart failure diagnosis, receiving ongoing HF management and without HF hospitalization within the prior 30 days. * Able and willing to provide written informed consent (or consent via a legally authorized representative, where applicable). * Meets all applicable domain-specific eligibility criteria for at least one active HEART Platform domain at the time of screening/randomization.
Exclusion criteria
(HEART Platform) * Participants will be excluded if any of the following apply: * Inability to provide informed consent (and no legally authorized representative available when applicable). * Not eligible for assignment to either HEART platform state (State 1 or State 2). * Presence of conditions or circumstances that, in the investigator's opinion, would make study participation unsafe or not feasible (e.g., inability to comply with study procedures or follow-up). * Does not meet the eligibility requirements for any active HEART Platform domain. * Any domain-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to first occurrence of all-cause death or cardiovascular hospitalization | Up to 365 days (or as defined in domain-specific protocol) | Time from randomization to the first event of all-cause death or cardiovascular hospitalization. This represents the platform default primary endpoint for Phase III domain evaluations. Outcomes for each intervention are defined within each HEART Platform domain protocol. The outcome measures listed in this registration represent platform-level outcomes and default endpoints used across domains where applicable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality | Up to 365 days | All-cause mortality after randomization. |
| Cardiovascular hospitalization | Up to 365 days | Occurrence of cardiovascular hospitalization after randomization. |
| Heart failure hospitalization | Up to 365 days | Occurrence of hospitalization due to worsening heart failure. |
| All-cause hospitalization | Up to 365 days | Occurrence of any hospitalization for any cause during the follow-up period of up to 365 days. |
| Quality-adjusted days alive and out of the hospital | Up to 365 days | Number of days alive and out of hospital following randomization, adjusted for health-related quality of life. |
| Organ-support free days | Up to 30 days | Number of days alive and free of organ support (e.g., mechanical ventilation, vasopressor therapy, or renal replacement therapy) within 30 days of enrollment. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score | Up to 365 days | KCCQ Overall Summary Score, a patient-reported measure of heart failure symptoms, physical and social function, and quality of life. Scores range from 0 to 100, with higher scores indicating better health status. Assessed at follow-up time points up to 365 days. |
| EQ-5D-5L Health Utility Score | Up to 365 days | Health-related quality of life measured using the EQ-5D-5L instrument. The EQ-5D-5L index score typically ranges from less than 0 (worse than death) to 1 (perfect health), with higher scores indicating better health status. Assessed at follow-up time points up to 365 days. |
Contacts
CONTACTJustin Ezekowitz, MD
PRINCIPAL_INVESTIGATORJustin Ezekowitz, MD
University of Alberta
Outcome results
None listed