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DETERMINE-preserved - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Preserved Ejection Fraction

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ClinicalTrials.gov Identifier: NCT03877224
Recruitment Status : Not yet recruiting
First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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 Preserved Ejection Fraction (HFpEF)

Condition or disease Intervention/treatment Phase
Heart Failure With Preserved Ejection Fraction (HFpEF) Drug: Dapagliflozin Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 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 Preserved Ejection Fraction
Estimated Study Start Date : April 5, 2019
Estimated Primary Completion Date : February 21, 2020
Estimated Study Completion Date : February 21, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dapagliflozin
Green, diamond shaped, film coated tablets 10 mg administered orally, once daily
Drug: Dapagliflozin
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.

Placebo Comparator: Placebo
Green, diamond shaped, film coated tablets placebo administered orally, once daily
Other: Placebo
Tablets administered orally once daily. Treatment start within 24h after randomisation for 16 weeks.




Primary Outcome Measures :
  1. Change from baseline in 6-minute walking distance (6MWD) at Week16 [ Time Frame: From baseline to Week16 ]
    To determine whether dapagliflozin is superior to placebo in increasing exercise capacity in patients with chronic heart failure New York Heart Association (NYHA) Functional Class II-IV and preserved ejection fraction (LVEF>40%)


Secondary Outcome Measures :
  1. Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Total symptom score (TSS) at Week16 [ Time Frame: From baseline to Week16 ]
    To determine whether dapagliflozin is superior to placebo in improving patient-reported HF symptoms. The KCCQ is a self administered 23 item instrument, measuring: physical functioning, symptoms, social functioning, self-efficacy and knowledge and quality of life. Scores are transformed to a range from 0-100 in which higher score reflects better outcome


Other Outcome Measures:
  1. Change from baseline at end of study (ie, the week starting at week 14) in mean movement intensity 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 movement intensity during walking.

  2. Change from baseline at end of study (ie, the week starting at week 14) in vector magnitude 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 vector magnitude units per minute.

  3. Change from baseline in serum NT-proBNP at Week16 [ Time Frame: From baseline to Week16 ]
    To determine whether dapagliflozin is superior to placebo in reducing serum N-terminal pro b-type natriuretic peptide (NT-proBNP)

  4. Change from baseline at end of study (ie, the week starting at week 14) in 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 in light to vigorous physical activity.

  5. Change from baseline in proportion of patients with worsened NYHA Functional Classification at Week16. [ Time Frame: From baseline to Week16 ]
    To determine whether dapagliflozin is superior to placebo in reducing the proportion of patients with worsened NYHA Functional Classification



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years to 150 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provision of signed informed consent prior to any study specific procedures
  • Male or female, aged ≥40 years
  • Established documented diagnosis of symptomatic HFpEF (NYHA functional class II-IV), which has been present for at least 8 weeks
  • LVEF>40% and evidence of structural heart disease
  • Elevated NT-proBNP levels
  • Patients should receive background standard of care as described below: All patients will be treated according to locally recognised guidelines on standard of care treatment for patients with HFpEF. Therapy should have been individually optimised and stable for ≥4 weeks (this does not apply to diuretics) and include (unless contraindicated or not tolerated) treatment of co morbidities (including high blood pressure, ischaemic heart disease, atrial fibrillation).
  • 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

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): NCT03877224


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

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Sponsors and Collaborators
AstraZeneca

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03877224     History of Changes
Other Study ID Numbers: D169EC00001
2018-003441-42 ( EudraCT Number )
First Posted: March 15, 2019    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: March 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs