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Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. (DELIVER)

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ClinicalTrials.gov Identifier: NCT03619213
Recruitment Status : Recruiting
First Posted : August 7, 2018
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE August 2, 2018
First Posted Date  ICMJE August 7, 2018
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE August 27, 2018
Estimated Primary Completion Date June 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 2, 2018)
Time to the first occurrence of any of the components of this composite: 1) CV death; 2) Hospitalisation for HF; 3) Urgent HF visit (e.g., emergency department or outpatient visit) [ Time Frame: Up to approximately 33 months ]
To determine whether dapagliflozin is superior to placebo, when added to standard of care, in reducing the composite of CV death and HF events (hospitalisation for HF or urgent HF visit) in patients with HF and preserved systolic function
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03619213 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 2, 2018)
  • Total number of (first and recurrent) hospitalisations for HF and CV death [ Time Frame: up to approximately 33 months ]
    To determine whether dapagliflozin is superior to placebo in reducing the total number of recurrent HF hospitalisations and CV death
  • Change from baseline in the total symptom score (TSS) of the KCCQ at 8 months [ Time Frame: Evaluated at 8 months after randomization ]
    To determine whether dapagliflozin is superior to placebo in improving Patient Reported Outcomes measured by KCCQ
  • Proportion of patients with worsened NYHA class from baseline to 8 months [ Time Frame: Evaluated at 8 months after randomization ]
    To determine whether dapagliflozin is superior to placebo in reducing the proportion of patients with worsened NYHA class
  • Time to the occurrence of death from any cause [ Time Frame: up to approximately 33 months ]
    To determine whether dapagliflozin is superior to placebo in reducing all-cause mortality
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 2, 2018)
Serious adverse events (SAEs), adverse events leading to treatment discontinuation (DAEs), amputations, adverse events (AEs) leading to amputation and potential risk factor AEs for amputations affecting lower limbs [ Time Frame: up to approximately 33 months ]
Safety: To evaluate the safety and tolerability of dapagliflozin compared to placebo in patients with HFpEF
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure.
Official Title  ICMJE An International, Double-blind, Randomised, Placebo-Controlled Phase III Study to Evaluate the Effect of Dapagliflozin on Reducing CV Death or Worsening Heart Failure in Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
Brief Summary This is an international, multicentre, parallel-group, event-driven, randomised, double-blind, placebo-controlled study in HFpEF patients, evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily in addition to background regional standard of care therapy, including treatments to control co-morbidities, in reducing the composite of CV death or heart failure events.
Detailed Description This is an international, multicentre, parallel-group, event-driven, randomised, double-blind study in patients with HFpEF, evaluating the effect of dapagliflozin 10 mg versus placebo, given once daily in addition to background regional standard of care therapy, including treatments to control co-morbidities, in reducing the composite of CV death and heart failure events (hospitalisations for HF or urgent HF visits). Adult patients aged ≥40 years with HFpEF (LVEF >40% and evidence of structural heart disease) and New York Heart Association (NYHA) class II-IV who are eligible according to the inclusion/exclusion criteria will be randomised in a 1:1 ratio to receive either dapagliflozin 10 mg or placebo. Both out-patients and in-patients hospitalised for heart failure and off intravenous heart failure-therapy for 24 hours can be randomised. It is estimated that approximately 8000 patients at 400-500 sites in 20-25 countries will need to be enrolled to reach the target of approximately 4700 randomised patients.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
International, Double-blind, Randomised, Placebo-Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Heart Failure With Preserved Ejection Fraction
Intervention  ICMJE
  • Drug: Dapagliflozin
    10 mg tablets given once daily, per oral use.
    Other Names:
    • Forxiga TM
    • Farxiga TM
  • Drug: Placebo
    Placebo matching dapagliflozin 10 mg
Study Arms  ICMJE
  • Experimental: Dapagliflozin
    Patients will be randomized 1:1 to either dapagliflozin or placebo.
    Intervention: Drug: Dapagliflozin
  • Placebo Comparator: Placebo
    Placebo matching dapagliflozin.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 2, 2018)
4700
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 22, 2021
Estimated Primary Completion Date June 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of signed informed consent prior to any study specific procedures.
  2. Male or female patients age ≥40 years.
  3. Documented diagnosis of symptomatic heart failure (NYHA class II-IV) at enrolment, and a medical history of typical symptoms/signs of heart failure ≥6 weeks before enrolment with at least intermittent need for diuretic treatment.
  4. Left Ventricular Ejection Fraction (LVEF) >40% and evidence of structural heart disease (i.e. left ventricular hypertrophy or left atrial enlargement ) documented by the most recent echocardiogram, and/or cardiac MR within the last 12 months prior to enrolment. For patients with prior acute cardiac events or procedures that may reduce LVEF, e.g. as defined in exclusion criterion 6, qualifying cardiac imaging assessment at least 12 weeks following the procedure/event is required.
  5. Elevated NT-pro BNP levels.
  6. Both ambulatory and hospitalised patients may be enrolled and randomised. Patients currently hospitalised for HF, must be off intravenous HF medications for at least 24 before randomisation.

Further details regarding inclusion criteria 4-6 may apply.

Exclusion Criteria:

  1. Receiving therapy with an SGLT2 inhibitor within 4 weeks prior to randomisation or previous intolerance to an SGLT2 inhibitor.
  2. Type 1 diabetes mellitus (T1D).
  3. eGFR <25 mL/min/1.73 m2 (CKD-EPI formula) at Visit 1.
  4. Systolic blood pressure (BP) <95 mmHg on 2 consecutive measurements at 5-minute intervals, at Visit 1 or at Visit 2.
  5. Systolic BP≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at 5-minute intervals, at Visit 1 or at Visit 2.
  6. MI, unstable angina, coronary revascularization (percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)), ablation of atrial flutter/fibrillation, valve repair/replacement within 12 weeks prior to enrolment. Before enrolment, these patients must have their qualifying echocardiography and/or cardiac MRI examination at least 12 weeks after the event.
  7. Planned coronary revascularization, ablation of atrial flutter/fibrillation and valve repair/replacement.
  8. Stroke or transient ischemic attack (TIA) within 12 weeks prior to enrolment.
  9. Probable alternative or concomitant diagnoses which in the opinion of the investigator could account for the patient's HF symptoms and signs (e.g. anaemia, hypothyroidism).
  10. Body mass index >50 kg/m2.

Further exclusion criteria may apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 40 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Listed Location Countries  ICMJE Argentina,   Bulgaria,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Hungary,   Japan,   Mexico,   Netherlands,   Peru,   Poland,   Romania,   Russian Federation,   Saudi Arabia,   Spain,   Taiwan,   United States,   Vietnam
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03619213
Other Study ID Numbers  ICMJE D169CC00001
2018-000802-46 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account AstraZeneca
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP