Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Short-term Effects of Dapagliflozin on Peak VO2 in HFrEF (DAPA-VO2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04197635
Recruitment Status : Completed
First Posted : December 13, 2019
Last Update Posted : April 27, 2022
Sponsor:
Information provided by (Responsible Party):
Julio Nuñez, Fundación para la Investigación del Hospital Clínico de Valencia

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.

Condition or disease Intervention/treatment Phase
Heart Failure With Reduced Ejection Fraction 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 Phase 4

Detailed Description:

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. This trial will include patients with stable symptomatic heart failure with reduced ejection fraction (HFrEF). 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. An intermediate clinical visit will be performed one week after study initiation.

Pre-and post-treatment evaluations (at baseline, 30 and 90 days) will include clinical assessment, cardiopulmonary exercise stress test, echocardiography, 6-minute walk test (6MWT), and quality of life indicators (Minnesota Living with Heart Failure Questionnaire -MLHFQ).

The investigators postulate that dapagliflozin 10 mg/day improves short-term functional capacity of patients with symptomatic HFrEF through multifactorial mechanisms, such as diuretic effect and improvement in myocardial energetic efficiency.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment
Official Title: Short-term Effects of Dapagliflozin on Peak VO2 in Patients With Heart Failure With Reduced Ejection Fraction
Actual Study Start Date : June 1, 2019
Actual Primary Completion Date : August 14, 2021
Actual Study Completion Date : April 19, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Active Comparator: Dapagliflozin 10 mg
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
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.
Other Name: peak oxygen consumption

Diagnostic Test: Echocardiography
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.
Other Name: Diastolic and Systolic function

Behavioral: Evaluation of health related quality of life
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.
Other Name: Quality of life

Diagnostic Test: Submáximal functional capacity assesment by 6 minutes walk 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.
Other Name: 6 minutes walk test

Other: Clinical evaluation
Evaluation of signs and symptoms of heart failure

Placebo Comparator: Placebo identical to dapagliflozin 10 mg
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
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.
Other Name: peak oxygen consumption

Diagnostic Test: Echocardiography
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.
Other Name: Diastolic and Systolic function

Behavioral: Evaluation of health related quality of life
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.
Other Name: Quality of life

Diagnostic Test: Submáximal functional capacity assesment by 6 minutes walk 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.
Other Name: 6 minutes walk test

Other: Clinical evaluation
Evaluation of signs and symptoms of heart failure




Primary Outcome Measures :
  1. Functional capacity [ Time Frame: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. ]
    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).


Secondary Outcome Measures :
  1. Left ventricular volumes [ Time Frame: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. ]

    The following parameters will be evaluated:

    Left ventricular diastolic volume (measured in milliliters, mL) and systolic volume (measured in milliliters, mL) It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.


  2. Left ventricular ejection fraction [ Time Frame: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. ]

    The following parameter will be evaluated:

    Left ventricular ejection fraction (measured by simpson method and expressed in percentage, %).

    It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.


  3. Left atrial volume [ Time Frame: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. ]

    The following parameter will be evaluated:

    Determination of 2-dimensional derived left atrial volume (volumen measured in milliliters, mL) indexed for body surface area (body surface area expressed in square meters -m2-) and expressed in mL/m2.

    It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.


  4. Echocardiographic parameters of diastolic function [ Time Frame: At baseline, 30 and 90 days after starting treatment with dapagliflozin or placebo. ]

    The following parameter of diastolic function will be evaluated:

    - E/e' ratio: value of E velocity-expressed in cm/s- / averaged value of septal and lateral side e´velocity - expressed in cm/s- of the mitral annulus by pulsed tissue Doppler.

    It will be performed by a trained cardiologist blind to study treatment at baseline and at 30 and 90 days after treatment initiation.


  5. Evaluation of health related quality of life by Minnesota Living with Heart Failure Questionnaire (MLHFQ) [ Time Frame: At 30 and 90 days after starting treatment with dapagliflozin or placebo. ]
    Assessment of the quality of life through the Minnesota Living with Heart Failure Questionnaire (MLHFQ). It will be completed at baseline and at 30 and 90 days after treatment initiation. The score values are ranged between 0 to 105 points.

  6. Submáximal functional capacity assesment by 6 minutes walk test [ Time Frame: at 30 and 90 days after starting treatment with dapagliflozin or placebo. ]
    It will be performed in an area equipped for cardiopulmonary resuscitation. Subjects will be asked not to perform 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 (measured in meters) 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04197635


Locations
Layout table for location information
Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Fundación para la Investigación del Hospital Clínico de Valencia
Investigators
Layout table for investigator information
Principal Investigator: Julio Nuñez Villota Fundación para la Investigación del Hospital Clínico de Valencia
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Julio Nuñez, Principal Investigator, Clinical Professor, Fundación para la Investigación del Hospital Clínico de Valencia
ClinicalTrials.gov Identifier: NCT04197635    
Other Study ID Numbers: ESR-17-13447(DAPA-HF)
2018-002614-12 ( EudraCT Number )
First Posted: December 13, 2019    Key Record Dates
Last Update Posted: April 27, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Julio Nuñez, Fundación para la Investigación del Hospital Clínico de Valencia:
Heart Failure with Reduced Ejection Fraction
Functional Capacity
Quality of life
Additional relevant MeSH terms:
Layout table for MeSH terms
Heart Failure
Heart Diseases
Cardiovascular Diseases