Feasibility Trial for a Right Ventricular Failure Platform Trial

NCT06570473 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CRAVE-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

The primary objective of the CRAVE feasibility trial is to assess the feasibility of conducting a larger CRAVE platform trial by performing a randomized trial of 30 participants with pulmonary hypertension and right ventricular dysfunction, comparing empagliflozin or ranolazine plus standard of care to standard of care alone.

Conditions

Pulmonary Hypertension; Right Ventricular Dysfunction; Right Heart Failure

Keywords

Pulmonary Hypertension; Right Ventricular Dysfunction; Right Heart Failure; Empagliflozin; Ranolazine

Outcome Measures

Primary Outcomes (5)

• The proportion of eligible participants approached that consent

  (target ≥30%)

  16 weeks

• The proportion of participants who consent that are randomized

  (target ≥90%)

  16 weeks

• Average enrolment rate of participants per centre per month

  (target ≥1 participant per centre/month)

  16 weeks

• Loss of follow up or death

  Loss of follow up (target at 16 weeks ≤5%)

  16 weeks

• Ability to capture data for secondary outcomes

  (target ≥90% completion)

  16 weeks

Secondary Outcomes (10)

• RV function

  16 weeks

• Natriuretic peptides

  16 weeks

• Hemodynamics

  16 weeks

• Exercise capacity measured virtually

  16 weeks

• Exercise capacity measured in-person

  16 weeks

Study Arms (3)

Empagliflozin

EXPERIMENTAL

Participants in the empagliflozin arm will receive 10 mg by mouth once daily and standard of care.

Drug: Empagliflozin

Ranolazine

EXPERIMENTAL

Participants in the ranolazine arm will receive ranolazine 500 mg by mouth twice daily, which will be increased to 1000 mg twice daily after 2 weeks (unless concurrently using moderate CYP 3A4 inhibitors, then dose is limited to 500 mg twice daily) and will receive standard of care.

Drug: Ranolazine

Standard of Care

NO INTERVENTION

Participants in this group will receive standard of care.

Interventions

Empagliflozin DRUG

Tablet

Also known as: Jardiance

Empagliflozin

Ranolazine DRUG

Tablet

Also known as: Corzyna

Ranolazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Able to provide informed consent.
• Able to comply with all study procedures.
• History of RV dysfunction or RHF secondary to any of:
• a. Group 1 PH, pulmonary arterial hypertension b. Group 2 PH, left heart disease with normal left ventricular ejection fraction (LVEF) \> 50% and a previous RHC demonstrating combined pre and post-capillary PH, defined as: i. mPAP \>20 mmHg ii. PAWP \> 15 mmHg iii. PVR\> 2 WU c. Group 3 PH d. Group 4 PH, chronic thromboembolic PH that is either persistent after pulmonary endarterectomy or inoperable due to distal disease.
• Symptomatic with current NYHA Functional Class II-IV
• Biomarker and 2D echocardiogram evidence of RV dysfunction within 3 months:
• NT-proBNP \>300 ng/L and qualitative evidence of at least 'mild' RV dysfunction on echocardiography OR NT-proBNP\<300 ng/L and qualitative evidence of at least moderate RV dysfunction and/or dilatation on 2D echocardiogram AND
• A quantitative 2D echocardiogram with evidence of RV dysfunction defined as having both of the following:
• i. TAPSE ≤18 mm ii. RV dilatation (RV diameter \> 42 mm at the base).
• Receiving loop diuretics or mineralocorticoid receptor antagonists for at least 4 weeks.
• Access to an iOS or android smart phone or tablet.

You may not qualify if:

• Estimated glomerular filtration rate (eGFR) \<30 ml/min.
• LVEF \< 50%
• Normal RV size and function
• Severe aortic or mitral valvular disease
• Moderate or severe hepatic dysfunction (Child-Pugh Class B or C)
• Participants requiring augmentation of diuretics or otherwise not meeting definition for clinical stability
• Pregnancy or lactation
• Unable to provide consent and comply with follow-up visits
• Listed for lung, heart or heart/lung transplantation
• Myocardial infarction or acute coronary syndrome within 90 days of screening
• Enrolled in another interventional trial
• Planned cardiac or thoracic surgical intervention in the next 6 months.
• Known hypersensitivity to empagliflozin or ranolazine.
• Concurrent treatment with:
• strong inhibitors of Cytochrome P450 3A4 (CYP 3A4), (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, nelfinavir, ritonavir, indinavir, saquinavir and grapefruit juice)

Sponsors & Collaborators

• University of Alberta: lead
• Canadian Heart Function Alliance: collaborator
• Accelerating Clinical Trials Consortium: collaborator
• Ottawa Heart Institute Research Corporation: collaborator
• Team PHenomenal Hope: collaborator

Study Sites (5)

University of Calgary

Calgary, Alberta, T1Y 6J4, Canada

NOT YET RECRUITING

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

RECRUITING

The University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

NOT YET RECRUITING

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5A5, Canada

NOT YET RECRUITING

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Hypertension, Pulmonary; Ventricular Dysfunction, Right; Heart Failure

Interventions

empagliflozin; Ranolazine

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Ventricular Dysfunction; Heart Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jason Weatherald, MD,MSc,FRCPC

  University of Alberta

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason Weatherald, MD,MSc,FRCPC

CONTACT

780-492-9937; weathera@ualberta.ca

Courtney Gubbels, BA

CONTACT

780-492-1113; courtney.gubbels@ualberta.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 26, 2024
• Study Start: July 15, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)