DETERMINE-reduced - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Reduced Ejection Fraction
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| ClinicalTrials.gov Identifier: NCT03877237 |
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Recruitment Status :
Completed
First Posted : March 15, 2019
Last Update Posted : March 23, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Heart Failure With Reduced Ejection Fraction (HFrEF) | Drug: Dapagliflozin Other: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 313 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | International, Multicentre, Parallel-group, Randomised, Double-blind, Placebo-controlled, Phase III Study Evaluating the Effect of Dapagliflozin on Exercise Capacity in Heart Failure Patients With Reduced Ejection Fraction |
| Actual Study Start Date : | April 9, 2019 |
| Actual Primary Completion Date : | March 7, 2020 |
| Actual Study Completion Date : | March 7, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Dapagliflozin
Green, diamond shaped, film coated tablets 10 mg administered orally, once daily
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Drug: Dapagliflozin
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks. |
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Placebo Comparator: Placebo
Green, diamond shaped, film coated tablets placebo administered orally, once daily
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Other: Placebo
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks. |
- Change from baseline in Kansas-City Cardiomyopathy Questionnaire-Total Symptom Score (KCCQ-TSS) at Week16 (higher scores represent less HF symptom frequency and burden). [ Time Frame: At baseline and at Week16 ]
To determine whether dapagliflozin is superior to placebo in patients with chronic heart failure with the New York Heart Association (NYHA) Functional Class II-IV (range I-IV, higher class represents worse functional class) and reduced ejection fraction (LVEF≤40%) [HFrEF] in:
- reducing patient-reported HF symptoms
- reducing patient-reported physical limitation
- improving exercise capacity
- Change from baseline in Kansas-City Cardiomyopathy Questionnaire-Physical Limitation Score (KCCQ-PLS) at Week16 (higher scores represent less physical limitation due to HF) [ Time Frame: At baseline and at Week16 ]
To determine whether dapagliflozin is superior to placebo in patients with chronic heart failure with the New York Heart Association (NYHA) Functional Class II-IV (range I-IV, higher class represents worse functional class) and reduced ejection fraction (LVEF≤40%) [HFrEF] in:
- reducing patient-reported HF symptoms
- reducing patient-reported physical limitation
- improving exercise capacity
- Change from baseline in 6-minute walk distance (6MWD) at Week16 (larger distances represent better functional capacity). [ Time Frame: At baseline and at Week16 ]
To determine whether dapagliflozin is superior to placebo in patients with chronic heart failure with the New York Heart Association (NYHA) Functional Class II-IV (range I-IV, higher class represents worse functional class) and reduced ejection fraction (LVEF≤40%) [HFrEF] in:
- reducing patient-reported HF symptoms
- reducing patient-reported physical limitation
- improving exercise capacity
- Change from baseline at the end of the study in the total time spent in light to vigorous physical activity, as assessed using a wearable activity monitor (accelerometer). [ Time Frame: From baseline until the week starting at Week14. ]To determine whether dapagliflozin is superior to placebo in increasing time spent non-sedentary, evaluated in a subset of at least 100 patients
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| Ages Eligible for Study: | 18 Years to 150 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Provision of signed informed consent prior to any study specific procedures
- Male or female, aged ≥18 years
- Documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 8 weeks
- LVEF≤40%
- Elevated NT-proBNP levels
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Patients should receive background standard of care as described below: All HFrEF patients should be treated according to locally recognised guidelines on standard of care treatment with both drugs and devices, as appropriate. Guideline-recommended medications should be used at recommended doses unless contraindicated or not tolerated. Therapy should have been individually optimised and stable for ≥4 weeks (this does not apply to diuretics) before visit 1 and include (unless contraindicated or not tolerated):
- an ACE inhibitor, or ARB or sacubitril/valsartan and
- a beta-blocker and
- if considered appropriate by the patient's treating physician; a mineral corticoid receptor antagonis
- 6MWD≥100 metres and ≤425 metres at enrolment and randomization.
Exclusion Criteria:
- Presence of any condition that precludes exercise testing
- Participation in a structured exercise training programme in the 1 month prior to screening or planned to start during the trial
- Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
- Type 1 diabetes mellitus
- eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at enrolment, unstable or rapidly progressing renal disease at time of randomisation
- Systolic BP <95 mmHg on 2 consecutive measurements
- Systolic BP ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements
- Current acute decompensated HF or hospitalisation due to decompensated HF <4 weeks prior to enrolment
- MI, unstable angina, coronary revascularization ablation of atrial flutter/fibrillation, valve repair/replacement, implantation of a cardiac resynchronization therapy device within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization.
- Stroke or transient ischemic attack within 12 weeks prior to enrolment.
- Primary pulmonary hypertension, chronic pulmonary embolism, severe pulmonary disease including COPD.
- Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
- HF due to infiltrative cardiomyopathy, active myocarditis, constrictive pericarditis, cardiac tamponade, known genetic hypertrophic cardiomyopathy or obstructive hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy/dysplasia, or uncorrected primary valvular disease
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): NCT03877237
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| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03877237 |
| Other Study ID Numbers: |
D169EC00002 2018-003442-16 ( EudraCT Number ) |
| First Posted: | March 15, 2019 Key Record Dates |
| Last Update Posted: | March 23, 2020 |
| Last Verified: | March 2020 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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