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NOT YET RECRUITING
NCT07857772
PHASE2

This Will be a Randomized Comparison of the Proteomic Effects of Vicadrostat/Empagliflozin Versus Empagliflozin and Versus Empagliflozin/Spironolactone in Heart Failure Patients With Preserved Ejection Fraction

Sponsor: Baim Institute for Clinical Research

View on ClinicalTrials.gov

Summary

The SPECTRA-HFpEF Study is a randomized, double-blind, Phase 2 clinical study designed to evaluate and compare the biological effects of vicadrostat in combination with empagliflozin, empagliflozin alone, and spironolactone in combination with empagliflozin in adults with heart failure and preserved ejection fraction. The study will enroll approximately 200 participants with chronic heart failure, New York Heart Association Class II to IV symptoms, and left ventricular ejection fraction greater than 40%. The primary objective is to determine whether treatment with vicadrostat/empagliflozin produces differential changes in circulating plasma proteins compared with spironolactone/empagliflozin, using a broad proteomic panel measured over the course of treatment. These proteomic changes may help identify biological pathways affected by each treatment strategy, including pathways related to inflammation, myocardial fibrosis and remodeling, kidney function, cardiac stress, and aldosterone-related signaling. Participants will complete an approximately 26-week study period, including screening, treatment, and follow-up phases. After screening and any required washout of prior sodium-glucose cotransporter 2 inhibitor therapy, participants will receive open-label empagliflozin and will be randomized in a blinded manner to receive vicadrostat or placebo during the first treatment period. During the second treatment period, participants will receive either continued vicadrostat with empagliflozin or spironolactone with empagliflozin. During the third treatment period, vicadrostat or spironolactone will be discontinued while empagliflozin is continued. Blood and urine samples will be collected at specified visits to evaluate changes in proteomic markers, renin-angiotensin-aldosterone system biomarkers, collagen turnover markers, sex hormone markers, kidney function, proteinuria, inflammatory biomarkers, and cardiac stress biomarkers. Echocardiography and patient-reported health status assessments will also be performed to explore potential effects on cardiac structure, function, symptoms, and quality of life. The study is intended to improve understanding of how aldosterone synthase inhibition with vicadrostat differs from mineralocorticoid receptor antagonism with spironolactone when each is used with empagliflozin in patients with heart failure and preserved ejection fraction. By comparing treatment-related proteomic and biomarker changes across study arms, the study may provide insight into mechanistic differences between these therapeutic approaches and help inform future development of targeted combination therapies for heart failure. Safety and tolerability will be monitored throughout the study through collection of adverse events, serious adverse events, vital signs, electrocardiograms, physical examinations, and clinical laboratory assessments, including kidney function and serum potassium monitoring.

Official title: A Randomized Comparison of the Proteomic Effects of Vicadrostat/Empagliflozin Versus Empagliflozin and Versus Empagliflozin/Spironolactone in Heart Failure Patients With Preserved Ejection Fraction

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

200

Start Date

2027-03

Completion Date

2028-09

Last Updated

2026-10-05

Healthy Volunteers

No

Interventions

DRUG

empa plus vica

Participants will be randomized to to this arm will receive empa (open-label)/vica (blinded). In treatment period 1 those randomized to empa/vica will be administered one tablet of empa 10 mg QD and one tablet of vica 10 mg QD for 8 weeks. In treatment period 2 for those randomized to empa/vica will continue to take empa 10 mg QD and vica 10 mg QD plus a placebo-matching spiro for 10 weeks. In treatment period 3, this group will receive open-label empa 10 mg QD for 4 weeks.

DRUG

Comparator: empa 10 plus spironolactone

For those randomized to empa (open-label) spiro (blinded), in treatment period 1 they will be administered one tablet of empa 10 mg QD and vica matching placebo for 8 weeks. In treatment period 2 for those randomized to empa/spiro, they will take empa 10 mg QD, spiro 25 mg titrating to 50 mg QD plus a vica matching placebo tablet for 10 weeks. In treatment period 3, this group will receive open-label empa 10 mg QD for 4 weeks.