Dapagliflozin Effects on Cardiometabolic Outcomes in Patients With an Acute Heart Attack.

Heart Failure Clinical Trial

— DAPA-MI  

Official title:

A Registry-based, Randomised, Double-blind, Placebo-Controlled Cardiovascular Outcomes Trial to Evaluate the Effect of Dapagliflozin on Cardiometabolic Outcomes in Patients Without Diabetes With Acute Myocardial Infarction at Increased Risk for Subsequent Development of Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04564742
• Other study ID #: D169DC00001
• Secondary ID: 2020-000664-31
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2020
• Est. completion date: July 5, 2023

Study information

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

Clinical Trial Summary

This study will evaluate the effect of dapagliflozin versus placebo, given once daily in addition to Standard of Care (SoC) therapies for patients with myocardial infarction (MI), for hospitalisation for heart failure (HHF), cardiovascular (CV) death, and other cardiometabolic outcomes.

Description:

This is a multicentre, parallel group double-blind, placebo-controlled phase 3 registry-based randomised controlled trial (R-RCT) in patients without diabetes presenting with myocardial infarction (MI) (ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI)) and evidence of impaired regional or global LV systolic function or definite evidence of Q wave MI on ECG. In the study the effect of dapagliflozin versus placebo, given once daily in addition to SoC therapy will be evaluated for the hospitalisation for HF, CV death, and other cardiometabolic outcomes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4017
• Est. completion date: July 5, 2023
• Est. primary completion date: July 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Participant must be =18 at the time of signing the informed consent

• Confirmed MI, either STEMI or NSTEMI, according to the fourth universal definition of MI (Thygesen et al 2019), within the preceding 7 days, or 10 days if earlier randomisation is not feasible

• Evidence of impaired regional or global LV systolic function at any timepoint during current MI-related hospitalisation (established with echocardiogram, radionuclide ventriculogram, contrast angiography or cardiac MRI) or definitive evidence on ECG of Q wave MI (defined as presence of Q waves in two or more contiguous leads, excluding leads III and aVR, and meeting all the following criteria: at least 1.5 mm in depth; at least 30 ms in duration; and, if R wave present, more than 25% of the size of the subsequent R wave)

• Hemodynamically stable at randomization (no episodes of symptomatic hypotension, or arrhythmia with haemodynamic compromise in the last 24 hours).

• Male or female

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol

• Provision of signed and dated, written informed consent prior to any mandatory study specific procedures, sampling, and analyses

Exclusion Criteria:

• Known type 1 diabetes mellitus (T1DM) or T2DM at the time for admission. Patients with hyperglycaemia, but without a diagnosis of diabetes mellitus prior to the index event, are eligible at the discretion of the Investigator. Patients who present with signs and symptoms consistent with ketoacidosis, including nausea, vomiting, abdominal pain, malaise and shortness of breath should be assessed for ketoacidosis, and if ketoacidosis is confirmed the patient should not be randomized.

• Chronic symptomatic HF with a prior HHF within the last year and known reduced ejection fraction (LVEF=40 %), documented before the current MI hospitalization

• Severe (eGFR <20 mL/min/1.73 m2 by local laboratory), unstable or rapidly progressing renal disease at the time of randomization

• Severe hepatic impairment (Child-Pugh class C) at the time of inclusion into the trial

• Active malignancy requiring treatment at the time of screening, except for basal cell- or squamous cell carcinoma of the skin, presumed possible to treat successfully

• Any non-CV condition, eg malignancy, with a life expectancy of less than two years based on the investigator´s clinical judgement

• Currently on treatment, or with an indication for treatment, with a sodium glucose co-transporter 2 inhibitor (SGLT2-inhibitor)

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Heart Failure
• Infarction
• Myocardial Infarction

Intervention

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

Locations

Country	Name	City	State
Sweden	Research Site	Alingsås
Sweden	Research Site	Borås
Sweden	Research Site	Eskilstuna
Sweden	Research Site	Falun
Sweden	Research Site	Gävle
Sweden	Research Site	Göteborg
Sweden	Research Site	Göteborg
Sweden	Research Site	Halmstad
Sweden	Research Site	Hässleholm
Sweden	Research Site	Helsingborg
Sweden	Research Site	Jönköping
Sweden	Research Site	Kalix
Sweden	Research Site	Karlshamn
Sweden	Research Site	Karlskoga
Sweden	Research Site	Karlskrona
Sweden	Research Site	Karlstad
Sweden	Research Site	Kiruna
Sweden	Research Site	Köping
Sweden	Research Site	Lidköping
Sweden	Research Site	Linköping
Sweden	Research Site	Lund
Sweden	Research Site	Malmö
Sweden	Research Site	Mölndal
Sweden	Research Site	Norrköping
Sweden	Research Site	Örebro
Sweden	Research Site	Östersund
Sweden	Research Site	Skellefteå
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Trollhättan
Sweden	Research Site	Umeå
Sweden	Research Site	Uppsala
Sweden	Research Site	Varberg
Sweden	Research Site	Värnamo
Sweden	Research Site	Västerås
Sweden	Research Site	Ystad
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Ashford
United Kingdom	Research Site	Basingstoke
United Kingdom	Research Site	Bath
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Blackpool
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Bridgend
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Buckhurst Hill
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Cardiff
United Kingdom	Research Site	Clydebank
United Kingdom	Research Site	Coventry
United Kingdom	Research Site	Derby
United Kingdom	Research Site	Dundee
United Kingdom	Research Site	East Kilbride
United Kingdom	Research Site	Edgbaston
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Exeter
United Kingdom	Research Site	Gillingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Harefield
United Kingdom	Research Site	Harrow
United Kingdom	Research Site	Headington
United Kingdom	Research Site	Hull
United Kingdom	Research Site	Kettering
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Lincoln
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Merthyr Tydfil
United Kingdom	Research Site	Middlesborough
United Kingdom	Research Site	Newcastle upon Tyne
United Kingdom	Research Site	Newport
United Kingdom	Research Site	Norwich
United Kingdom	Research Site	Nottingham
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Pontyclun
United Kingdom	Research Site	Portsmouth
United Kingdom	Research Site	Rhyl
United Kingdom	Research Site	Scarborough
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Southampton
United Kingdom	Research Site	Stevenage
United Kingdom	Research Site	Stoke on Trent
United Kingdom	Research Site	Sunderland
United Kingdom	Research Site	Swansea
United Kingdom	Research Site	Taunton
United Kingdom	Research Site	Torquay
United Kingdom	Research Site	Truro
United Kingdom	Research Site	Wakefield
United Kingdom	Research Site	Wigan
United Kingdom	Research Site	Wolverhampton
United Kingdom	Research Site	Worcester
United Kingdom	Research Site	Worthing

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Uppsala University

Countries where clinical trial is conducted

Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The hierarchical composite endpoint of Death (CV death followed by non-CV death), Hosp due to heart failure (adjudicated followed by investigator reported), Non-fatal MI, AF/flutter event, New onset of T2DM, last visit NYHA class, and weight loss =5%		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	The hierarchical composite endpoint of Death (CV death followed by non-CV death), Hospitalisation due to heart failure (adjudicated followed by investigator reported), Non-fatal MI, AF/flutter event, New onset of T2DM, and last visit NYHA class		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to the first occurrence of any of the components of this composite: • HHF • CV death		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to the first occurrence of any of the components of this composite: • MI • Stroke (incl. ischaemic, haemorrhagic and undetermined stroke) • CV death		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to CV death		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to the first occurrence of a fatal or a non-fatal MI		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to new onset of T2DM		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Change from baseline in Body weight		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to hospitalisation for any cause		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient
Secondary	Time to death of any cause		From randomization visit up to approximately 30 months, with a minimum follow-up time of at least 3 months for each patient