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)

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ClinicalTrials.gov Identifier: NCT03036124

Recruitment Status : Completed

First Posted : January 30, 2017

Results First Posted : September 1, 2020

Last Update Posted : September 1, 2020

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

Tracking Information

First Submitted Date ^ICMJE

January 26, 2017

First Posted Date ^ICMJE

January 30, 2017

Results First Submitted Date ^ICMJE

July 6, 2020

Results First Posted Date ^ICMJE

September 1, 2020

Last Update Posted Date

September 1, 2020

Actual Study Start Date ^ICMJE

February 8, 2017

Actual Primary Completion Date

July 17, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure or Urgent Visit Due to Heart Failure. [ Time Frame: Up to 27.8 months. ]

Primary efficacy

Original Primary Outcome Measures ^ICMJE

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

Current Secondary Outcome Measures ^ICMJE

Subjects Included in the Composite Endpoint of CV Death or Hospitalization Due to Heart Failure. [ Time Frame: Up to 27.8 months. ]
Secondary
Events Included in the Composite Endpoint of Recurrent Hospitalizations Due to Heart Failure and CV Death. [ Time Frame: Up to 27.8 months. ]
Secondary
Change From Baseline in the KCCQ Total Symptom Score [ Time Frame: Baseline and 8 months or death before 8 months ]
KCCQ is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The KCCQ total symptom score incorporates the symptom domains into a single score. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.
Subjects Included in the Composite Endpoint of ≥50% Sustained Decline in eGFR, ESRD or Renal Death. [ Time Frame: Up to 27.8 months. ]
Secondary
Subjects Included in the Endpoint of All-cause Mortality. [ Time Frame: Up to 27.8 months. ]
Secondary

Original Secondary Outcome Measures ^ICMJE

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 ^ICMJE

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 ^ICMJE

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 ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition ^ICMJE

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)

Intervention ^ICMJE

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 ^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 *

* 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

Completed

Actual Enrollment ^ICMJE

4744

Original Estimated Enrollment ^ICMJE

4500

Actual Study Completion Date ^ICMJE

July 17, 2019

Actual Primary Completion Date

July 17, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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 ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years to 130 Years (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

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 ^ICMJE

NCT03036124

Other Study ID Numbers ^ICMJE

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 ^ICMJE

Not Provided

Responsible Party

AstraZeneca

Study Sponsor ^ICMJE

AstraZeneca

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

AstraZeneca

Verification Date

August 2020

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

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