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

Heart Failure With Preserved Ejection Fraction Clinical Trial

— DELIVER  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03619213
• Other study ID #: D169CC00001
• Secondary ID: 2018-000802-46
• Status: Completed
• Phase: Phase 3
• Start date: August 27, 2018
• Est. completion date: March 27, 2022

Study information

• Verified date: July 2023
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 11000 patients at approximately 400-500 sites in 20-25 countries will need to be enrolled to reach the target of approximately 6100 randomised patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6263
• Est. completion date: March 27, 2022
• Est. primary completion date: March 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 130 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

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

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Catamarca
Argentina	Research Site	Ciudad Autonoma de Buenos Aire
Argentina	Research Site	Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	Cordoba
Argentina	Research Site	Córdoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Ramos Mejía
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Argentina	Research Site	San Nicolás
Argentina	Research Site	Santa Fe
Belgium	Research Site	Aalst
Belgium	Research Site	Brasschaat
Belgium	Research Site	Bruxelles
Belgium	Research Site	Huy
Belgium	Research Site	Kortrijk
Belgium	Research Site	Leuven
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Belo Horizonte
Brazil	Research Site	Blumenau
Brazil	Research Site	Campina Grande do Sul
Brazil	Research Site	Campinas
Brazil	Research Site	Campinas
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Votuporanga
Bulgaria	Research Site	Dimitrovgrad
Bulgaria	Research Site	Haskovo
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pleven
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	Stara Zagora
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Brampton	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Cambridge	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Laval	Quebec
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Newmarket	Ontario
Canada	Research Site	North York	Ontario
Canada	Research Site	Oshawa	Ontario
Canada	Research Site	Port Perry	Ontario
Canada	Research Site	Saint-Jerome	Quebec
Canada	Research Site	Scarborough	Ontario
Canada	Research Site	Terrebonne	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Trois-Rivieres	Quebec
Canada	Research Site	Waterloo	Ontario
Canada	Research Site	Winnipeg	Manitoba
Canada	Research Site	York	Ontario
China	Research Site	Baotou
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Cangzhou
China	Research Site	Changchun
China	Research Site	Changchun
China	Research Site	Chengdu
China	Research Site	Chifeng
China	Research Site	Dalian
China	Research Site	Daqing
China	Research Site	Fuzhou
China	Research Site	Fuzhou
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Haerbin
China	Research Site	Jinan
China	Research Site	Lanzhou
China	Research Site	Nanchang
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Nanjing
China	Research Site	Pingxiang
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Wuhan
China	Research Site	Xi'an
China	Research Site	Yinchuan
Czechia	Research Site	Benesov
Czechia	Research Site	Brandys nad Labem
Czechia	Research Site	Brno
Czechia	Research Site	Jaromer
Czechia	Research Site	Kladno
Czechia	Research Site	Louny
Czechia	Research Site	Nachod
Czechia	Research Site	Ostrava-Dubina
Czechia	Research Site	Pardubice
Czechia	Research Site	Praha 2
Czechia	Research Site	Pribram
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Gyor
Hungary	Research Site	Kecskemét
Hungary	Research Site	Miskolc
Hungary	Research Site	Nyíregyháza
Hungary	Research Site	Székesfehérvár
Hungary	Research Site	Szekszárd
Hungary	Research Site	Szentes
Hungary	Research Site	Szolnok
Hungary	Research Site	Zalaegerszeg
Japan	Research Site	Adachi-ku
Japan	Research Site	Asahi-shi
Japan	Research Site	Azumino-shi
Japan	Research Site	Beppu-shi
Japan	Research Site	Chuo-ku
Japan	Research Site	Fujisawa-shi
Japan	Research Site	Fujisawa-shi
Japan	Research Site	Funabashi-shi
Japan	Research Site	Hachioji-shi
Japan	Research Site	Hamada-shi
Japan	Research Site	Hamamatsu-shi
Japan	Research Site	Higashiohmi-shi
Japan	Research Site	Ichinomiya-shi
Japan	Research Site	Iizuka-shi
Japan	Research Site	Iwakuni-shi
Japan	Research Site	Kanazawa-shi
Japan	Research Site	Kasugai-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Koga-shi
Japan	Research Site	Kuki-shi
Japan	Research Site	Kure-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Mito-shi
Japan	Research Site	Miura-gun
Japan	Research Site	Nakagami-gun
Japan	Research Site	Nishinomiya-shi
Japan	Research Site	Oita-shi
Japan	Research Site	Saga-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Suita-shi
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Takasago-shi
Japan	Research Site	Toride-shi
Japan	Research Site	Tsu-shi
Japan	Research Site	Tsuchiura-shi
Japan	Research Site	Ueda-shi
Japan	Research Site	Ureshino-shi
Japan	Research Site	Utsunomiya-shi
Mexico	Research Site	Aguascalientes
Mexico	Research Site	Culiacán
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mazatlán
Mexico	Research Site	Mexico
Mexico	Research Site	México
Mexico	Research Site	Monclova
Mexico	Research Site	Monterey
Mexico	Research Site	Monterrey
Mexico	Research Site	Querétaro
Mexico	Research Site	Tijuana
Mexico	Research Site	Veracruz
Mexico	Research Site	Veracruz
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Arnhem
Netherlands	Research Site	Den Haag
Netherlands	Research Site	Dordrecht
Netherlands	Research Site	Groningen
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Leiderdorp
Netherlands	Research Site	Meppel
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Uden
Netherlands	Research Site	Veldhoven
Peru	Research Site	Bellavista
Peru	Research Site	Callao
Peru	Research Site	Chancay
Peru	Research Site	Chorrillos
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	San Isidro
Peru	Research Site	Urb. El Chipe
Poland	Research Site	Bialystok
Poland	Research Site	Bochnia
Poland	Research Site	Chojnice
Poland	Research Site	Gdansk
Poland	Research Site	Gdynia
Poland	Research Site	Gdynia
Poland	Research Site	Jaslo
Poland	Research Site	Katowice
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Olawa
Poland	Research Site	Opole
Poland	Research Site	Plock
Poland	Research Site	Rzeszów
Poland	Research Site	Torun
Poland	Research Site	Wierzchoslawice
Poland	Research Site	Wroclaw
Romania	Research Site	Brasov
Romania	Research Site	Craiova
Romania	Research Site	Iasi
Romania	Research Site	Iasi
Romania	Research Site	Iasi
Romania	Research Site	Tg Mures
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Moscow
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	Tver
Saudi Arabia	Research Site	Dammam
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Jeddah
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Saudi Arabia	Research Site	Riyadh
Spain	Research Site	A Coruña
Spain	Research Site	Barcelona
Spain	Research Site	Hospitalet de Llobregat(Barcel
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Sanlúcar De Barrameda (Cádiz)
Spain	Research Site	Santiago(A Coruña)
Spain	Research Site	Sevilla
Spain	Research Site	Valencia
Spain	Research Site	Valencia
Spain	Research Site	Villamartín (Cádiz)
Taiwan	Research Site	Hsinchu
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Taichung
Taiwan	Research Site	Tainan
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei
Taiwan	Research Site	Taipei City
Taiwan	Research Site	Taoyuan City
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Anderson	Indiana
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bay City	Michigan
United States	Research Site	Beaumont	Texas
United States	Research Site	Beverly Hills	California
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Bridgewater	New Jersey
United States	Research Site	Buffalo	New York
United States	Research Site	Burlington	Vermont
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chicago	Illinois
United States	Research Site	Chicago	Illinois
United States	Research Site	Clearwater	Florida
United States	Research Site	Doylestown	Pennsylvania
United States	Research Site	Fairhope	Alabama
United States	Research Site	Falls Church	Virginia
United States	Research Site	Flint	Michigan
United States	Research Site	Flint	Michigan
United States	Research Site	Great Falls	Montana
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Gurnee	Illinois
United States	Research Site	Hammond	Louisiana
United States	Research Site	Houma	Louisiana
United States	Research Site	Humble	Texas
United States	Research Site	Jackson	Tennessee
United States	Research Site	Kansas City	Missouri
United States	Research Site	Kansas City	Missouri
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Leesburg	Virginia
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Loma Linda	California
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mobile	Alabama
United States	Research Site	Monroe	Louisiana
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Munster	Indiana
United States	Research Site	Naples	Florida
United States	Research Site	Nashville	Tennessee
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Ocala	Florida
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Providence	Rhode Island
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Augustine	Florida
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Paul	Minnesota
United States	Research Site	Sheffield	Alabama
United States	Research Site	Sherman	Texas
United States	Research Site	Stamford	Connecticut
United States	Research Site	Tucson	Arizona
United States	Research Site	Tullahoma	Tennessee
United States	Research Site	Wilmington	North Carolina
Vietnam	Research Site	Hanoi
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,  Belgium,  Brazil,  Bulgaria,  Canada,  China,  Czechia,  Hungary,  Japan,  Mexico,  Netherlands,  Peru,  Poland,  Romania,  Russian Federation,  Saudi Arabia,  Spain,  Taiwan, 

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.	Dual primary efficacy; Primary endpoint analysed in all patients randomised (Full analysis set).; The analysis was assessed on Full Analysis Set, including events occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months
Primary	Subjects Included in the Composite Endpoint of CV Death, Hospitalization Due to Heart Failure or Urgent Visit Due to Heart Failure for LVEF <60% Subpopulation	Dual primary efficacy; Primary endpoint analysed in all patients randomised with LVEF < 60% at baseline.; The analysis was assessed on Full Analysis Set, including events occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months
Secondary	Events Included in the Composite Endpoint of CV Death or Recurrent Heart Failure Event (Hospitalization Due to Heart Failure or Urgent Heart Failure Visit)	Secondary efficacy; Total number of heart failure events (first and recurrent) and cardiovascular death, analysed in all randomized patients.; The analysis was assessed on Full Analysis Set, including events occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months
Secondary	Events Included in the Composite Endpoint of CV Death or Recurrent Heart Failure Event (Hospitalization Due to Heart Failure or Urgent Heart Failure Visit) for LVEF <60% Subpopulation	Secondary efficacy; Total number of heart failure events (first and recurrent) and cardiovascular death, analysed in all randomized patients with LVEF < 60% at baseline; The analysis was assessed on Full Analysis Set, including events occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months
Secondary	Change From Baseline in the KCCQ Total Symptom Score at 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.	Baseline and 8 months or death before 8 months
Secondary	Subjects Included in the Endpoint of Cardiovascular Death	Secondary efficacy; The analysis was assessed on Full Analysis Set, including deaths occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months
Secondary	Subjects Included in the Endpoint of All-cause Mortality	Secondary efficacy; The analysis was assessed on Full Analysis Set, including deaths occurring on or prior to Primary Analysis Censoring Date.	Up to 42.1 months

External Links

•   Redacted Clinical Study Protocol
•   Redacted CSR Synopsis
•   Redacted Statistical Analysis Plan