Heart Failure Efficacy and Research Trial (HEART) Platform (HEART)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Other: Domain Intervention(s); Other: Control / Standard of Care Comparator

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.

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Justin Ezekowitz, MD; Phone Number: 780-492-0712; Email: jae2@ualberta.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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 exclusion criteria applicable to the intervention/domain(s) for which the participant would otherwise be eligible.
• Additional inclusion and exclusion criteria apply for each individual HEART Platform domain and will be specified in the relevant domain protocol(s).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active Domain Intervention(s); Participants will be randomized to receive one of the active intervention strategies being evaluated within eligible HEART Platform domains at the time of randomization. Eligible domains and interventions may change over time as domains are initiated, modified, or closed.	Other: Domain 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.
Placebo Comparator: Control / Standard of Care Comparator; Participants will be randomized to a concurrent control group within eligible HEART Platform domains. The control group may include placebo and/or standard-of-care management, as specified in each active domain protocol.	Other: Control / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first occurrence of all-cause death or cardiovascular hospitalization	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.	Up to 180 days (or as defined in domain-specific protocol)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular hospitalization	Occurrence of cardiovascular hospitalization after randomization.	Up to 180 days
All-cause mortality	All-cause mortality after randomization.	Up to 180 days
Heart failure hospitalization	Occurrence of hospitalization due to worsening heart failure.	Up to 180 days
Days Alive and Out of Hospital	Number of days alive and out of hospital following randomization.	Up to 180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS)	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Total Symptom Score from baseline to Day 5 comparing treatment groups. The Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) ranges from 0 to 100, where higher scores indicate fewer heart failure symptoms and better health status, and lower scores indicate more severe symptoms and worse health status.	Baseline to Day 90)
Safety outcomes (Serious Adverse Events)	Incidence of serious adverse events (SAEs) and adverse events of special interest, as defined in the master protocol and domain protocols.	Up to 30 days (or through end of treatment/participation)

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Canadian VIGOUR Centre
• Investigators: Principal Investigator: Justin Ezekowitz, MD, University of Alberta

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): March 1, 2036
• Study Completion (Estimated): March 1, 2037

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: February 19, 2026
• First Posted (Actual): February 23, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: HEART-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No