Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure (DAPA-HF)

• ClinicalTrials.gov Identifier: NCT03036124
• Recruitment Status: Completed
• First Posted: January 30, 2017
• Last Update Posted: August 15, 2019
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: January 26, 2017
• First Posted Date: January 30, 2017
• Last Update Posted Date: August 15, 2019
• Actual Study Start Date: February 8, 2017
• Actual Primary Completion Date: July 17, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 17, 2017): Time to the first occurrence of any of the components of the composite: CV death or hospitalization for HF or an urgent HF visit. [ Time Frame: From randomization visit (day 0) up to approximately 3 years ]
• Original Primary Outcome Measures (submitted: January 26, 2017): Time to the first occurrence of any of the components of the composite: CV death or hospitalization for HF or an urgent HF visit. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
• Change History: Complete list of historical versions of study NCT03036124 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: January 16, 2018)

• Time to the first occurrence of either of the components of the composite: CV death or hospitalization for HF. [ Time Frame: From randomization visit (day 0) up to approximately 3 years ]
• Total number of (first and recurrent) HF hospitalizations and CV death. [ Time Frame: From randomization visit (day 0) up to approximately 3 years ]
• Change from baseline measured at 8 months in the total symptom score of the Kansas City Cardiomyopathy Questionnaire (KCCQ), a specific HF patient reported outcome questionnaire. [ Time Frame: From randomization visit (day 0) up to 8 months (day 240) ]
• Time to the first occurrence of any of the components of the composite: ≥50% sustained decline in eGFR or reaching End Stage Renal Disease (ESRD) or renal death. [ Time Frame: From randomization visit (day 0) up to approximately 3 years ]
  End Stage Renal Disease (ESRD) is defined as;

  • Sustained eGFR <15 mL/min/1.73m^2 or,
  • Chronic dialysis treatment or,
  • Receiving a renal transplant
• Time to death from any cause. [ Time Frame: From randomization visit (day 0) up to approximately 3 years ]

Original Secondary Outcome Measures (submitted: January 26, 2017)

• Time to the first occurrence of either of the components of the composite: CV death or hospitalization for HF. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
• Total number of (first and recurrent) HF hospitalizations and CV death. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
• Change from baseline measured at 8 months in the clinical summary score of the KCCQ, a specific HF patient reported outcome questionnaire. [ Time Frame: From randomization visit (day 0) up to 8 months (day 240) ]
• Time to the first occurrence of any of the components of the composite: ≥50% sustained decline in eGFR or reaching End Stage Renal Disease (ESRD) or renal death. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]
  End Stage Renal Disease (ESRD) is defined as;

  • Sustained eGFR <15 ml/min/1.73m2 or,
  • Chronic dialysis treatment or,
  • Receiving a renal transplant
• Time to death from any cause. [ Time Frame: From randomization visit (day 0) up to approximatley 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure
• Official Title: Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure With Reduced Ejection Fraction
• Brief Summary: The purpose of this study is to evaluate the effect of dapagliflozin on the incidence of worsening heart failure or cardiovascular death in patients with chronic heart failure with reduced ejection fraction
• Detailed Description: This is an international, multicentre, parallel group, event-driven, randomized, double-blind, placebo-controlled study in patients with chronic heart failure with reduced ejection fraction (HFrEF), evaluating the effect of dapagliflozin versus placebo, given once daily in addition to background regional standard of care therapy, for the prevention of cardiovascular (CV) death or reduction of heart failure (HF) events.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Intervention

• Drug: Dapagliflozin
  10 mg or 5 mg tablets given once daily, per oral use.
  Other Names:

  • Forxiga TM
  • Farxiga TM
• Drug: Placebo
  Placebo matching dapagliflozin 10 mg or 5 mg.

Study Arms

• 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 *: McMurray JJV, DeMets DL, Inzucchi SE, Køber L, Kosiborod MN, Langkilde AM, Martinez FA, Bengtsson O, Ponikowski P, Sabatine MS, Sjöstrand M, Solomon SD; DAPA-HF Committees and Investigators. The Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial: baseline characteristics. Eur J Heart Fail. 2019 Jul 15. doi: 10.1002/ejhf.1548. [Epub ahead of print]

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 12, 2018): 4744
• Original Estimated Enrollment (submitted: January 26, 2017): 4500
• Actual Study Completion Date: July 17, 2019
• Actual Primary Completion Date: July 17, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Provision of signed informed consent prior to any study specific procedures
• Male or female, aged ≥18 years
• Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV), which has been present for at least 2 months
• LVEF≤40%
• Elevated NT-proBNP levels
• Patients should receive background standard of care for HFrEF and be treated according to locally recognized guidelines
• eGFR ≥30 mL/min/1.73 m^2 (CKD-EPI formula) at enrolment (visit 1)

Exclusion Criteria:

• Receiving therapy with an SGLT2 inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
• Type 1 diabetes mellitus
• Symptomatic hypotension or systolic BP <95 mmHg at 2 out of 3 measurements either at visit 1 or visit 2
• Current acute decompensated HF or hospitalization due to decompensated HF <4 weeks prior to enrolment
• MI, unstable angina, stroke or transient ischemic attack within 12 weeks prior to enrolment
• Coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization
• Implantation of a CRT 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 primary valvular disease
• Symptomatic bradycardia or second or third degree heart block without a pacemaker
• Severe (eGFR <30 mL/min/1.73 m^2 by CKD-EPI), unstable or rapidly progressing renal disease at the time of randomization

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 130 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Germany, Hungary, India, Japan, Netherlands, Poland, Russian Federation, Slovakia, Sweden, Taiwan, United Kingdom, United States, Vietnam
• Removed Location Countries: Czech Republic

Administrative Information

• NCT Number: NCT03036124
• Other Study ID Numbers: D1699C00001; 2016-003897-41 ( 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

• IPD Sharing Statement: Not Provided
• Responsible Party: AstraZeneca
• Study Sponsor: AstraZeneca
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: August 2019