HFrEFPhase 2NCT04956809
Effect of Dapagliflozin on Submaximal Exercise Tolerance in Heart Failure
A Phase 2 study testing Dapagliflozin 10Mg Tab in people with HFrEF, run by University of Pennsylvania at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HFrEF
- What is being tested?
- Dapagliflozin 10Mg Tab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Oct 2021to 1 Jun 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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)
- Clinically significant lung disease as defined by: Chronic Obstructive Pulmonary Disease meeting Stage III or greater GOLD criteria (FEV1<50% predicted), treatment with oral steroids within the past 6 months for an exacerbation of obstructive lung disease, current use of supplemental oxygen aside from nocturnal oxygen for the treatment of obstructive sleep apnea.
- Desaturation to <90% on the baseline maximal effort cardiopulmonary exercise test will also be grounds for exclusion
- Clinically-significant ischemia, as per investigator's judgement, on stress testing without either (1) subsequent revascularization, (2) an angiogram demonstrating the absence of clinically significant epicardial coronary artery disease, as per investigator judgment; (3) a follow-up 'negative' stress test, particularly when using a more specific technique (i.e., a negative perfusion imaging test following a 'positive' ECG stress test)
- Exercise induced regional wall motion abnormalities suggestive of ongoing ischemia during the baseline maximal effort cardiopulmonary exercise test will be exclusionary
- Implantation of a CRT device within 12 weeks prior to enrollment or intent to implant a CRT device during the study period
- Previous cardiac transplantation or implantation of a ventricular assist device, or implantation expected after randomization
- Symptomatic bradycardia or second- or third-degree heart block, in the absence of a pacemaker
- Significant liver disease impacting synthetic function or volume control (ALT/AST > 3x ULN, Albumin < 3.0 g/dL)
- Severe right ventricular dysfunction
- Baseline resting seated systolic blood pressure > 180 mmHg or <90 mmHg
- Orthostatic blood pressure response to the transition from supine to standing (>20 mmHg reduction in systolic blood pressure 2-3 minutes after standing)
- Active participation in another study that utilizes an investigational agent (observational studies/registries allowed)
- Any condition that, in the opinion of the investigator, will interfere with the completion of the study. This may include comorbid or psychiatric conditions that may impede successful completion of the protocol, or logistical concerns (e.g. inability to travel to the exercise unit).
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Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19054
About this study
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
- Being tested
- Dapagliflozin 10Mg Tab, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10Mg TabDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin 10mg | Active comparator | Active arm will be 6 weeks in duration, separated by a 2-week wash-out period. Receives: Drug: Dapagliflozin 10Mg Tab |
| Placebo | Placebo comparator | Placebo arm will be 6 weeks in duration, separated by a 2-week wash-out period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo.
Measured: 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2021
- Study start22 Oct 2021
- Primary completion1 Jun 2023
- Study completion1 Jun 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HFrEFStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Kenneth B Margulies, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04956809
- Sponsor's protocol ID
- 848538
- Status last verified
- Dec 2023
- First submitted
- 30 Jun 2021
- Last updated
- 12 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Dapagliflozin on Submaximal Exercise Tolerance in Heart Failure
- ClinicalTrials.gov ID
- NCT04956809
- Acronym / sponsor ID
- 848538
- Conditions
- HFrEF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 22 Oct 2021 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Jun 2023 (actual)
- First posted
- 9 Jul 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin 10mg | Active comparator | Drug: Dapagliflozin 10Mg TabActive arm will be 6 weeks in duration, separated by a 2-week wash-out period. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo arm will be 6 weeks in duration, separated by a 2-week wash-out period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (29 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dapagliflozin 10Mg TabThis 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. | Drug | Dapagliflozin 10mg |
| PlaceboThis 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. | Drug | Placebo |
Primary outcome
The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo.
Time frame: 24 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Dapagliflozin 10Mg Tab in people with HFrEF, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint will be the change in submaximal exercise endurance (time to exhaustion at 75% of peak workload) between Dapa and placebo. (time frame: 24 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2023.