PRIMA-HF: Predicting Myocardial Recovery in Heart Failure Using Cardiac Imaging HAI-HF: High Dosing vs. Standard Dosing Adenosine During Myocardial Perfusion in Heart Failure (PRIMA-HF)

December 19, 2025 updated by: Sarah Lindhøj Kvorning, Gødstrup Hospital

PRIMA-HF PRedicting Recovery of Left Ventricular Function With Multimodality Cardiac IMAging in Patients With de Novo Heart Failure HAI-HF: High-Dose Adenosine During Perfusion Imaging in Heart Failure: Rationale and Design of the HAI-HF Trial

Background:

Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous condition with variable potential for left ventricular ejection fraction (LVEF) recovery. While LVEF improvement and reverse remodeling predict better outcomes, the determinants that predict left ventricular recovery remain poorly understood. An expert panel of the Journal of American College of Cardiology highlighted the need for improved HFrEF phenotyping to clarify recovery patterns and support personalized management and risk stratification.

Methods:

PRIMA-HF is a prospective prediction study designed to determine whether baseline cardiac multimodality imaging can predict LVEF recovery in patients with de novo HFrEF (n=180). The imaging protocol includes cardiac magnetic resonance (CMR), coronary computed tomography and [¹⁵O]H₂O positron emission tomography ([¹⁵O]H₂O-PET) and echocardiography. Patients will also undergo a six-minute walk test, blood volume measurement, and blood sampling. The primary outcome is the change in LVEF from baseline to approx. after 3-12 months (or after full optitration in GDMT), assessed by CMR.

In 60 patients from the PRIMA-HF cohort, the randomized, double-blind study High Dose Adenosine During Perfusion Imaging in Heart Failure (HAI-HF) will be conducted. HAI-HF evaluates whether high-dose adenosine (210 µg/kg/min) versus standard-dose (140 µg/kg/min) during [¹⁵O]H₂O-PET changes the stress myocardial blood flow, which is the primary endpoint.

Aim:

The PRIMA-HF study comprehensively characterizes patients with newly diagnosed HFrEF through multimodality imaging and systematically assesses change in LVEF using CMR. The study's deep phenotyping approach integrates clinical, imaging, biomarker, and functional data to capture disease heterogeneity, rather than relying on traditional measures such as LVEF or symptom class. This enables the identification of distinct patient subgroups with shared pathophysiological mechanisms.

The HAI-HF trial examines whether higher adenosine doses improve [¹⁵O]H₂O-PET perfusion imaging in HFrEF.

Together, the studies will advance understanding of myocardial recovery, improve perfusion assessment, and support development of a predictive model for HFrEF prognosis.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Herning, Denmark, 7400
        • University Clinic of Cardiovascular Reseach

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years
  • Capable and has provided written informed consent
  • LVEF ≤ 40% by echocardiography in connection with hospitalization for heart failure or in connection with outpatient evaluation for heart failure

Exclusion Criteria:

  • Previous diagnosis of heart failure
  • Unable to understand the patient information
  • Pregnancy, as the study involves ionizing radiation.
  • Current severe valvular disease (as defined by the Danish national treatment guidelines on cardio.dk)
  • Atrial fibrillation with a heart rate > 130 beats per minute during the inclusion echocardiography
  • Cardiac surgery within 6 months prior to inclusion
  • Acute exacerbation of existing chronic obstructive pulmonary disease
  • Severe asthma or chronic obstructive pulmonary disease with FEV1 < 1L
  • any contraindication for adenosine stress testing
  • Severe renal failure < 15 mL/min/1.73m² or dialysis
  • Advanced liver disease (Child-Pugh class C)
  • Endocarditis at inclusion/baseline
  • Isolated right-sided heart failure
  • Malignant disease treated with chemotherapy or radiotherapy, or expected life expectancy under 1 year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low-dose then High-dose Adenosine
Diagnostic test: HAI-HF: Adenosine Stress [¹⁵O]H₂O PET Imaging
HAI-HF: Patients will be randomized in a 1:1 ratio to one of two dosing sequences: high-dose followed by low-dose adenosine, or low-dose followed by high-dose adenosine.
Drug: Two different doses of adenosine
Testing if high dose adenosine (210 ug/kg/min) during perfusion imaging results in a higher myocardial blood flow compared to standard dose (140 ug/kg/min) in patients with HFrEF
Experimental: High-dose then Low-dose Adenosine
Diagnostic test: HAI-HF: Adenosine Stress [¹⁵O]H₂O PET Imaging
HAI-HF: Patients will be randomized in a 1:1 ratio to one of two dosing sequences: high-dose followed by low-dose adenosine, or low-dose followed by high-dose adenosine.
Drug: Two different doses of adenosine
Testing if high dose adenosine (210 ug/kg/min) during perfusion imaging results in a higher myocardial blood flow compared to standard dose (140 ug/kg/min) in patients with HFrEF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PRIMA-HF: Left ventricular ejection fraction (LVEF)
Time Frame: PRIMA-HF: Baseline through study completion, an average of 3 months
Change in LVEF (continuous variable, absolute change in LVEF in percent points)
PRIMA-HF: Baseline through study completion, an average of 3 months
HAI-HF: Stress Myocardial Blood Flow (MBF)
Time Frame: Baseline and periprocedural
Change in stress MBF (continuous variable, ml/min/g)
Baseline and periprocedural

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PRIMA-HF: Kansas City Cardiomyopathy Questionaire (KCCQ-12)
Time Frame: Baseline through study completion, an average of 3 months
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) (points, continuous data)
Baseline through study completion, an average of 3 months
PRIMA-HF: 6 minutes-walk-test
Time Frame: Baseline through study completion, an average of 3 months
Change in 6MWT distance (meters, continuous data)
Baseline through study completion, an average of 3 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
PRIMA-HF: Blood volume
Time Frame: Baseline through study completion, an average of 3 months
Change in blodvolume (L, continuous data)
Baseline through study completion, an average of 3 months
PRIMA-HF: NT-Pro-BNP
Time Frame: Baseline through study completion, an average of 3 months
Change in NT-Pro-BNP (pg/mL or pmol/L, continuous data)
Baseline through study completion, an average of 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gødstrup Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 8, 2025

Primary Completion (Estimated)

April 30, 2029

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

November 17, 2025

First Submitted That Met QC Criteria

November 17, 2025

First Posted (Estimated)

November 21, 2025

Study Record Updates

Last Update Posted (Actual)

December 26, 2025

Last Update Submitted That Met QC Criteria

December 19, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1-10-72-126-25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The study will adhere to all applicable regulations and guidelines governing the transfer of individual participantdata (IPD), which will be biological material (blood samples), abroad, ensuring that all data are handled confidentially and in full compliance with relevant legislation.

IPD Sharing Time Frame

Data sharing is planned after the enrollment of 200 patients in PRIMA-HF, which is anticipated to be achieved by the end of 2027. Approximately two months thereafter, we expect to have completed the necessary analyses, at which point the availability of individual participant data will cease.

Upon completion of the project, collaborating partners will destroy all data in accordance with our agreements and applicable requirements.

IPD Sharing Access Criteria

We plan to send biological material for proteomics measurements for further analysis to either deCODE, Reykjavik, Iceland, or Olink, Uppsala, Sweden. This will only take place after legal approval has been obtained in the Central Denmark Region.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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