Effect of Dapagliflozin on Submaximal Exercise Tolerance in Heart Failure

NCT04956809 | Completed Phase 2 FDA Drug

• 1 other identifier: 848538
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine whether and how the FDA-approved drug dapagliflozin (Dapa) improves submaximal exercise endurance and skeletal muscle oxidative phosphorylation capacity (SkM OxPhos) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF).

Conditions

HFrEF

Outcome Measures

Primary Outcomes (1)

• The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo.

  24 Months

Study Arms (2)

Dapagliflozin 10mg

ACTIVE COMPARATOR

Active arm will be 6 weeks in duration, separated by a 2-week wash-out period.

Drug: Dapagliflozin 10Mg Tab

Placebo

PLACEBO COMPARATOR

Placebo arm will be 6 weeks in duration, separated by a 2-week wash-out period.

Drug: Placebo

Interventions

Dapagliflozin 10Mg Tab DRUG

This will be a single-center randomized, placebo controlled, double-blind, 2-treatment, 2-phase cross-over trial in 27 HFrEF subjects: (A) Dapa 10 mg daily; (B) Placebo.

Dapagliflozin 10mg

Placebo DRUG

This will be a single-center randomized, placebo controlled, double-blind, 2-treatment, 2-phase cross-over trial in 27 HFrEF subjects: (A) Dapa 10 mg daily; (B) Placebo.

Placebo

Eligibility Criteria

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

You may qualify if:

• Diagnosis of HFrEF with NYHA Class II-III functional class, which has been present for at least two months
• Left ventricular ejection fraction ≤ 40%
• Stable medical therapy for at least 1 month
• Plasma NT-proBNP level of: ≥ 200pg/mL; OR ≥ 125pg/mL if they were hospitalized for HF within the past 12 months; or ≥ 250 pg/mL if patient had atrial fibrillation/flutter on baseline ECG

You may not qualify if:

• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrollment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes mellitus
• Age \<18 years old
• Pregnancy: Women of childbearing potential will undergo a urine pregnancy test during the screening visit.
• Uncontrolled atrial fibrillation, as defined by a resting heart rate \> 100 beats per minute at the time of the baseline assessment
• Paroxysmal atrial fibrillation (Afib) or flutter with \>1 hour of continuous Afib documented within the previous 6 months (prior to screening or randomization), direct-current (DC) cardioversion or ablation procedure for Afib within 6 months, or plan to attempt to restore sinus rhythm (with drug therapy, ablation, or DC cardioversion) within 6 months of randomization. Subjects with persistent Afib and no sinus rhythm documented in the prior 6 months are permitted.
• Hemoglobin \< 10 g/dL
• eGFR \< 25 mL/min/1.73m\^2, or unstable or rapidly progressing renal disease at the time of randomization
• Subject inability/unwillingness to exercise
• Greater than moderate left sided valvular disease (mitral regurgitation, aortic stenosis, aortic regurgitation), moderate or greater mitral stenosis, severe right-sided valvular disease
• Known hypertrophic, infiltrative, restrictive or inflammatory cardiomyopathy
• Clinically significant pericardial disease, as per investigator judgment
• Current angina due to clinically significant epicardial coronary disease, as per investigator judgment
• Acute coronary syndrome or coronary intervention within the past 2 months
• Primary pulmonary artery hypertension (WHO Group 1 Pulmonary Arterial Hypertension)

Sponsors & Collaborators

• University of Pennsylvania: lead
• Amgen: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19054, United States

Location

MeSH Terms

Interventions

dapagliflozin

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 9, 2021
• Study Start: October 22, 2021
• Primary Completion: June 1, 2023
• Study Completion: June 1, 2023
• Last Updated: December 12, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)