Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure

Chronic Heart Failure With Reduced Ejection Fraction (HFrEF) Clinical Trial

— DAPA-HF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03036124
• Other study ID #: D1699C00001
• Secondary ID: 2016-003897-41
• Status: Completed
• Phase: Phase 3
• Start date: February 8, 2017
• Est. completion date: July 17, 2019

Study information

• Verified date: August 2020
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4744
• Est. completion date: July 17, 2019
• Est. primary completion date: July 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Heart Failure With Reduced Ejection Fraction (HFrEF)
• Heart Failure

Intervention

Drug:
• Dapagliflozin
10 mg or 5 mg tablets given once daily, per oral use.
• Placebo
Placebo matching dapagliflozin 10 mg or 5 mg.

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autonoma Buenos Aires
Argentina	Research Site	Ciudad Autonoma de Buenos Aire
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	Córdoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Esperanza
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Quilmes
Argentina	Research Site	Quilmes
Argentina	Research Site	Ramos Mejía
Argentina	Research Site	Rosario
Argentina	Research Site	Rosario
Argentina	Research Site	San Luis
Argentina	Research Site	San Martin
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Nicolás
Argentina	Research Site	Santa Fe
Argentina	Research Site	Vicente Lopez
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Brasilia
Brazil	Research Site	Brasillia
Brazil	Research Site	Campina Grande do Sul
Brazil	Research Site	Campinas
Brazil	Research Site	Curitiba
Brazil	Research Site	Goiânia
Brazil	Research Site	Marilia
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Uberlandia
Brazil	Research Site	Votuporanga
Bulgaria	Research Site	Blagoevgrad
Bulgaria	Research Site	Dimitrovgrad
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kyustendil
Bulgaria	Research Site	Lom
Bulgaria	Research Site	Pleven
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Canada	Research Site	Abbotsford	British Columbia
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	New Westminster	British Columbia
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	North Vancouver	British Columbia
Canada	Research Site	North York	Ontario
Canada	Research Site	Oakville	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Peterborough	Ontario
Canada	Research Site	Port Perry	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Rimouski	Quebec
Canada	Research Site	Saint John	New Brunswick
Canada	Research Site	Saint-Jerome	Quebec
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Terrebonne	Quebec
Canada	Research Site	Waterloo	Ontario
Canada	Research Site	York	Ontario
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Bengbu
China	Research Site	Changchun
China	Research Site	Changsha
China	Research Site	Chifeng
China	Research Site	Dalian
China	Research Site	Guangzhou
China	Research Site	Haerbin
China	Research Site	Lanzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Ningbo
China	Research Site	Pingxiang
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Shenzhen
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xuzhou
China	Research Site	Xuzhou
China	Research Site	Yinchuan
China	Research Site	Zhuhai
Czechia	Research Site	Benesov
Czechia	Research Site	Brno
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Czechia	Research Site	Louny
Czechia	Research Site	Ostrava-Dubina
Czechia	Research Site	Plzen
Czechia	Research Site	Praha
Czechia	Research Site	Praha 2
Czechia	Research Site	Praha 4
Czechia	Research Site	Praha 5
Czechia	Research Site	Trebic
Denmark	Research Site	Hellerup
Denmark	Research Site	Herlev
Denmark	Research Site	Hvidovre
Denmark	Research Site	København Ø
Denmark	Research Site	Odense C
Denmark	Research Site	Svendborg
Germany	Research Site	Bad Oeynhausen
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Dresden
Germany	Research Site	Dresden
Germany	Research Site	Hamburg
Germany	Research Site	Homburg
Germany	Research Site	Kassel
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	Papenburg
Germany	Research Site	Stuttgart
Germany	Research Site	Wermsdorf
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Kecskemét
Hungary	Research Site	Mosonmagyaróvár
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Hungary	Research Site	Szentes
Hungary	Research Site	Zalaegerszeg
India	Research Site	Ahmedabad
India	Research Site	Aurangabad
India	Research Site	Bangalore
India	Research Site	Belagavi
India	Research Site	Ernakulam
India	Research Site	Gurgaon
India	Research Site	Kanpur
India	Research Site	Karamsad
India	Research Site	Kolkata
India	Research Site	Maharashtra
India	Research Site	Nadiad
India	Research Site	Nagpur
India	Research Site	Nagpur
India	Research Site	New Delhi
India	Research Site	Pune
India	Research Site	Pune
Japan	Research Site	Adachi-ku
Japan	Research Site	Aki-gun,
Japan	Research Site	Azumino-shi
Japan	Research Site	Beppu-shi
Japan	Research Site	Bunkyo-ku
Japan	Research Site	Chikushino-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fujisawa-shi
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Japan	Research Site	Fukuoka-shi
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Japan	Research Site	Hiratsuka-shi
Japan	Research Site	Hitachinaka-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Itabashi-ku
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Japan	Research Site	Kasama-shi
Japan	Research Site	Kishiwada-shi
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Japan	Research Site	Matsumoto-shi
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Japan	Research Site	Nishinomiya-shi
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Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakai-shi,Kita-ku
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sanyoonoda-shi
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Japan	Research Site	Sendai-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Shimonoseki-shi
Japan	Research Site	Shinjuku-ku
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Japan	Research Site	Tachikawa-shi
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Japan	Research Site	Takasaki-shi
Japan	Research Site	Toride-shi
Japan	Research Site	Tsuchiura-shi
Japan	Research Site	Tsukuba-shi
Japan	Research Site	Ueda-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Wakayama-shi
Japan	Research Site	Wako-shi
Japan	Research Site	Yokohama-shi
Netherlands	Research Site	Apeldoorn
Netherlands	Research Site	Den Bosch
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Gouda
Netherlands	Research Site	Groningen
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Sneek
Netherlands	Research Site	Veldhoven
Poland	Research Site	Bochnia
Poland	Research Site	Gdynia
Poland	Research Site	Jaslo
Poland	Research Site	Katowice
Poland	Research Site	Kedzierzyn Kozle
Poland	Research Site	Kraków
Poland	Research Site	Legnica
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olawa
Poland	Research Site	Plock
Poland	Research Site	Sokólka
Poland	Research Site	Torun
Poland	Research Site	Wierzchoslawice
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Gatchina
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	Tver
Russian Federation	Research Site	Yekaterinburg
Slovakia	Research Site	Brezno
Slovakia	Research Site	Kosice
Slovakia	Research Site	Lucenec
Slovakia	Research Site	Martin
Slovakia	Research Site	Nove Zamky
Slovakia	Research Site	Presov
Slovakia	Research Site	Svidnik
Slovakia	Research Site	Trebisov
Slovakia	Research Site	Trnava
Slovakia	Research Site	Zilina
Sweden	Research Site	Göteborg
Sweden	Research Site	Lund
Sweden	Research Site	Ostersund
Sweden	Research Site	Stockholm
Sweden	Research Site	Umeå
Taiwan	Research Site	Changhua City
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kweishan Shiang
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
United Kingdom	Research Site	Airdrie
United Kingdom	Research Site	Clydebank
United Kingdom	Research Site	Cottingham
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Inverness
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Paisley
United States	Research Site	Alexandria	Louisiana
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bakersfield	California
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bangor	Maine
United States	Research Site	Beaumont	Texas
United States	Research Site	Beverly Hills	California
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Bridgewater	New Jersey
United States	Research Site	Bronx	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Burlington	North Carolina
United States	Research Site	Chalmette	Louisiana
United States	Research Site	Cleveland	Ohio
United States	Research Site	Columbia	Maryland
United States	Research Site	Columbus	Ohio
United States	Research Site	Cortlandt Manor	New York
United States	Research Site	Cumming	Georgia
United States	Research Site	Dallas	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Fairhope	Alabama
United States	Research Site	Falls Church	Virginia
United States	Research Site	Farmington	Utah
United States	Research Site	Flint	Michigan
United States	Research Site	Flint	Michigan
United States	Research Site	Grand Island	Nebraska
United States	Research Site	Great Falls	Montana
United States	Research Site	Haverhill	Massachusetts
United States	Research Site	Hazel Crest	Illinois
United States	Research Site	Houston	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jerseyville	Illinois
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kingwood	Texas
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Lake Worth	Florida
United States	Research Site	Lansing	Michigan
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Memphis	Tennessee
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mobile	Alabama
United States	Research Site	Naples	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	New Brunswick	New Jersey
United States	Research Site	New Smyrna Beach	Florida
United States	Research Site	New York	New York
United States	Research Site	Omaha	Nebraska
United States	Research Site	Orchard Park	New York
United States	Research Site	Palm Springs	California
United States	Research Site	Pembroke Pines	Florida
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Poughkeepsie	New York
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Richmond	Virginia
United States	Research Site	Rosedale	New York
United States	Research Site	Saint Augustine	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas
United States	Research Site	Seattle	Washington
United States	Research Site	Seattle	Washington
United States	Research Site	Sheffield	Alabama
United States	Research Site	Somerset	New Jersey
United States	Research Site	Stockton	California
United States	Research Site	Torrance	California
United States	Research Site	Tucker	Georgia
United States	Research Site	Tullahoma	Tennessee
United States	Research Site	Tupelo	Mississippi
United States	Research Site	Tyler	Texas
United States	Research Site	Vista	California
United States	Research Site	Wellington	Florida
United States	Research Site	Wilmington	Delaware
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Hcmc
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh
Vietnam	Research Site	Ho Chi Minh

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Denmark,  Germany,  Hungary,  India,  Japan,  Netherlands,  Poland,  Russian Federation,  Slovakia,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure or Urgent Visit Due to Heart Failure.	Primary efficacy	Up to 27.8 months.
Secondary	Subjects Included in the Composite Endpoint of CV Death or Hospitalization Due to Heart Failure.	Secondary	Up to 27.8 months.
Secondary	Events Included in the Composite Endpoint of Recurrent Hospitalizations Due to Heart Failure and CV Death.	Secondary	Up to 27.8 months.
Secondary	Change From Baseline in the KCCQ Total Symptom Score	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.	Baseline and 8 months or death before 8 months
Secondary	Subjects Included in the Composite Endpoint of =50% Sustained Decline in eGFR, ESRD or Renal Death.	Secondary	Up to 27.8 months.
Secondary	Subjects Included in the Endpoint of All-cause Mortality.	Secondary	Up to 27.8 months.

External Links

•   redacted protocol
•   redacted Statistical Analysis Plan