Short-term Effects of Dapagliflozin on Peak VO2 in HFrEF

NCT04197635 | Completed Phase 4 DMC

• 2 other identifiers: ESR-17-13447(DAPA-HF)2018-002614-12
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be a double-blind multicenter randomized study (1:1) to evaluate the effect of dapagliflozin 10 mg per day or placebo on short-term functional capacity evaluated through changes in peak oxygen consumption.

Conditions

Heart Failure With Reduced Ejection Fraction

Keywords

Heart Failure with Reduced Ejection Fraction; Functional Capacity; Quality of life

Outcome Measures

Primary Outcomes (1)

• Functional capacity

  Changes in peak oxygen consumption (VO2) at baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. VO2 is only one measure and is expressed as milliliters of oxygen per kilogram of body weight per minute (oxygen in milliliters, weight in kilograms, and time in minutes and expressed in ml/kg/min).

  At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.

Secondary Outcomes (6)

• Left ventricular volumes

  At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.

• Left ventricular ejection fraction

  At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.

• Left atrial volume

  At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.

• Echocardiographic parameters of diastolic function

  At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo.

• Evaluation of health related quality of life by Minnesota Living with Heart Failure Questionnaire (MLHFQ)

  At 30 and 90 days after starting treatment with dapagliflozin or placebo.

Study Arms (2)

Dapagliflozin 10 mg

ACTIVE COMPARATOR

After providing informed consent, patients will be randomly assigned to receive dapagliflozin 10 mg per day.

Diagnostic Test: Maximal functional capacity by cardiopulmonary exercise testing; Diagnostic Test: Echocardiography; Behavioral: Evaluation of health related quality of life; Diagnostic Test: Submáximal functional capacity assesment by 6 minutes walk test; Other: Clinical evaluation

Placebo identical to dapagliflozin 10 mg

PLACEBO COMPARATOR

After providing informed consent, patients will be randomly assigned to receive placebo (one tablet a day orally).

Diagnostic Test: Maximal functional capacity by cardiopulmonary exercise testing; Diagnostic Test: Echocardiography; Behavioral: Evaluation of health related quality of life; Diagnostic Test: Submáximal functional capacity assesment by 6 minutes walk test; Other: Clinical evaluation

Interventions

Maximal functional capacity by cardiopulmonary exercise testing DIAGNOSTIC_TEST

It will be done with cycle ergometer (CORTEX Metamax3B), starting with 10W of power and increasing 10W every minute. During the test, heart rate, rhythm and blood pressure will be monitored. Gas exchange data shall be evaluated every 10 seconds and the peak oxygen consumption (peak VO2) shall be considered the maximum value obtained during the last 20 seconds of exercise. The main parameters to be determined are: maximum functional capacity, peak VO2, slope of the VE/VCO2 ratio, and chronotropic incompetence variables. It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.

Also known as: peak oxygen consumption

Dapagliflozin 10 mg; Placebo identical to dapagliflozin 10 mg

Echocardiography DIAGNOSTIC_TEST

The following parameters will be evaluated: a)left ventricular volumes; b) left ventricular systolic function; and c)left atrial volume and E/e' ratio. It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.

Also known as: Diastolic and Systolic function

Dapagliflozin 10 mg; Placebo identical to dapagliflozin 10 mg

Evaluation of health related quality of life BEHAVIORAL

Assessment of the quality of life through the Minnesota Living with Heart Failure Questionnaire (MLHFQ), Spanish version. It will be completed at baseline and at 30 and 90 days after treatment initiation. The score of the questionnaire is 0 to 105 points.

Also known as: Quality of life

Dapagliflozin 10 mg; Placebo identical to dapagliflozin 10 mg

Submáximal functional capacity assesment by 6 minutes walk test DIAGNOSTIC_TEST

It will be performed in an area equipped for cardiopulmonary resuscitation. Subjects will be asked not to perform a vigorous physical exercise in the previous 2 hours. They will be allowed to have a light meal before the test. Before the test, the vital signs will be determined in a seated position after a rest of 10 minutes. Subjects will be instructed to walk at their own pace to cover as much distance as possible in 6 minutes. It will be performed by a trained nurse blind to study treatment at baseline and at 30 and 90 days after treatment initiation.

Also known as: 6 minutes walk test

Dapagliflozin 10 mg; Placebo identical to dapagliflozin 10 mg

Clinical evaluation OTHER

Evaluation of signs and symptoms of heart failure

Dapagliflozin 10 mg; Placebo identical to dapagliflozin 10 mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant or his legal representative is willing and able to give informed consent for participation in the study.
• Male or female, aged ≥18 years.
• Established documented diagnosis of symptomatic HF (NYHA functional class II-III), which has been present for at least 2 months.
• LVEF ≤40% documented in the last 3 months by echocardiography or cardiac magnetic resonance.
• NT-proBNP ≥600 pg/ml.
• Patients should receive background standard of care for HFrEF at judgment of the investigator.
• Estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73m2 (DMRD formula) at enrolment.

You may not qualify if:

• Inability to perform a valid (respiratory exchange ratio -RER- ≥1.05) baseline cardiopulmonary exercise test (CPET)
• Patients receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment, or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes
• Symptomatic hypotension or systolic blood pressure \<95 mmHg
• Current acute decompensated HF or hospitalization due to decompensated HF \<4 weeks prior to enrolment
• Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 12 weeks prior to enrolment
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or cardiac valve repair/replacement within 12 weeks prior to enrolment, or planned to undergo any of these operations after randomization
• Implantation of a cardiac resynchronization therapy (CRT) device within 12 weeks prior to enrolment or intent to implant a CRT device
• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
• HF due to restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic (obstructive) cardiomyopathy, or uncorrected severe primary cardiac valve disease
• Symptomatic bradycardia or second or third-degree heart block without a pacemaker
• Severe renal dysfunction (eGFR\<30 ml/min/1.73m2) or prior admission for acute renal failure in the last 4 weeks.
• Pregnant or lactating women
• Woman of childbearing age, unless they are using highly effective contraceptive methods.
• Patients with severe hepatic impairment (Child-Pugh class C).

Sponsors & Collaborators

• Fundación para la Investigación del Hospital Clínico de Valencia: lead

Study Sites (1)

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (4)

• Nunez J, Palau P, Dominguez E, Mollar A, Nunez E, Ramon JM, Minana G, Santas E, Facila L, Gorriz JL, Sanchis J, Bayes-Genis A. Early effects of empagliflozin on exercise tolerance in patients with heart failure: A pilot study. Clin Cardiol. 2018 Apr;41(4):476-480. doi: 10.1002/clc.22899. Epub 2018 Apr 17.

  PMID: 29663436 BACKGROUND

• Lorenzo M, Jacobs-Cacha C, Palau P, Amiguet M, Seller J, Nunez E, Espriella R, Gorriz JL, Minana G, Sanchis J, Bayes-Genis A, Soler MJ, Packer M, Nunez J; DAPA-VO2 Investigators. Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status. JACC Heart Fail. 2023 Nov;11(11):1611-1622. doi: 10.1016/j.jchf.2023.07.010. Epub 2023 Sep 6.

  PMID: 37676213 DERIVED

• Amiguet M, Palau P, Dominguez E, Seller J, Pinilla JMG, de la Espriella R, Minana G, Valle A, Sanchis J, Gorriz JL, Bayes-Genis A; DAPA VO2 investigators; Nunez J. Dapagliflozin and short-term changes on circulating antigen carbohydrate 125 in heart failure with reduced ejection fraction. Sci Rep. 2023 Jun 30;13(1):10591. doi: 10.1038/s41598-023-37491-5.

  PMID: 37391470 DERIVED

• Palau P, Amiguet M, Dominguez E, Sastre C, Mollar A, Seller J, Garcia Pinilla JM, Larumbe A, Valle A, Gomez Doblas JJ, de la Espriella R, Minana G, Mezcua AR, Santas E, Bodi V, Sanchis J, Pascual-Figal D, Gorriz JL, Bayes-Genis A, Nunez J; DAPA-VO2 Investigators (see Appendix). Short-term effects of dapagliflozin on maximal functional capacity in heart failure with reduced ejection fraction (DAPA-VO2 ): a randomized clinical trial. Eur J Heart Fail. 2022 Oct;24(10):1816-1826. doi: 10.1002/ejhf.2560. Epub 2022 Jun 6.

  PMID: 35604416 DERIVED

MeSH Terms

Interventions

Echocardiography; Diastole; Quality of Life; Walk Test

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Myocardial Contraction; Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Muscle Relaxation; Muscle Contraction; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Health Status; Demography; Epidemiologic Measurements; Public Health; Environment and Public Health; Exercise Test

Study Officials

• Julio Nuñez Villota

  Fundación para la Investigación del Hospital Clínico de Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: After providing informed consent, patients will be randomly assigned, with a remote, web-based computer-generated block randomization procedure in an allocation 1:1 ratio, to either receive dapagliflozin 10 mg per day or placebo (one tablet a day orally). This system will allow the maintenance of the randomization codes and the opening of them if necessary. Investigators and patients will be blinded to treatment allocations. Knowing that no treatment crossings between both groups are expected, there is no need of planning washing periods.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Clinical Professor

Model Details: This study will be a double-blind multicenter randomized study (1:1) to evaluate the effect of dapagliflozin 10 mg per day or placebo on short-term functional capacity evaluated through changes in peak oxygen consumption The patients will be randomized to receive dapagliflozin or placebo. Once the inclusion criteria are fulfilled and the informed consent signed, patients will be randomized, and efficacy endpoints will be evaluated at 3 time points: 1) baseline (before dapagliflozin/placebo administration), 2) 30 days after randomization, and, 3) 90 days after randomization.

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: December 13, 2019
• Study Start: June 1, 2019
• Primary Completion: August 14, 2021
• Study Completion: April 19, 2022
• Last Updated: April 27, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)