Clinical trial NCT04564742: Dapagliflozin Effects on Cardiometabolic Outcomes in Patients With an Acute Heart Attack.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Myocardial Infarction
Heart Failure
Keywords: Myocardial Infarction
Cardiovascular Outcome Trial
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Uppsala University
First posted: 2020-09-25
Enrollment: 4017
Sex: ALL
Minimum age (years): 18
Maximum age (years): 130
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Analysis of the Hierarchical Primary Composite Endpoint (Full Analysis Set)
timeFrame: 29 months
Secondary outcomes:
Other outcomes:
Locations:
city: Alingsås
country: Sweden
facility: Research Site
city: Borås
country: Sweden
facility: Research Site
city: Eskilstuna
country: Sweden
facility: Research Site
city: Falun
country: Sweden
facility: Research Site
city: Gävle
country: Sweden
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Halmstad
country: Sweden
facility: Research Site
city: Helsingborg
country: Sweden
facility: Research Site
city: Hässleholm
country: Sweden
facility: Research Site
city: Jönköping
country: Sweden
facility: Research Site
city: Kalix
country: Sweden
facility: Research Site
city: Karlshamn
country: Sweden
facility: Research Site
city: Karlskoga
country: Sweden
facility: Research Site
city: Karlskrona
country: Sweden
facility: Research Site
city: Karlstad
country: Sweden
facility: Research Site
city: Kiruna
country: Sweden
facility: Research Site
city: Köping
country: Sweden
facility: Research Site
city: Lidköping
country: Sweden
facility: Research Site
city: Linköping
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Malmö
country: Sweden
facility: Research Site
city: Mölndal
country: Sweden
facility: Research Site
city: Norrköping
country: Sweden
facility: Research Site
city: Skellefteå
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Trollhättan
country: Sweden
facility: Research Site
city: Umeå
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
city: Varberg
country: Sweden
facility: Research Site
city: Värnamo
country: Sweden
facility: Research Site
city: Västerås
country: Sweden
facility: Research Site
city: Ystad
country: Sweden
facility: Research Site
city: Örebro
country: Sweden
facility: Research Site
city: Östersund
country: Sweden
facility: Research Site
city: Aberdeen
country: United Kingdom
facility: Research Site
city: Ashford
country: United Kingdom
facility: Research Site
city: Basingstoke
country: United Kingdom
facility: Research Site
city: Bath
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Blackpool
country: United Kingdom
facility: Research Site
city: Bradford
country: United Kingdom
facility: Research Site
city: Bridgend
country: United Kingdom
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Buckhurst Hill
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Clydebank
country: United Kingdom
facility: Research Site
city: Coventry
country: United Kingdom
facility: Research Site
city: Derby
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: East Kilbride
country: United Kingdom
facility: Research Site
city: Edgbaston
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Gillingham
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Harefield
country: United Kingdom
facility: Research Site
city: Harrow
country: United Kingdom
facility: Research Site
city: Headington
country: United Kingdom
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
city: Kettering
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Lincoln
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Merthyr Tydfil
country: United Kingdom
facility: Research Site
city: Middlesborough
country: United Kingdom
facility: Research Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Research Site
city: Newport
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Pontyclun
country: United Kingdom
facility: Research Site
city: Portsmouth
country: United Kingdom
facility: Research Site
city: Rhyl
country: United Kingdom
facility: Research Site
city: Scarborough
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
city: Stevenage
country: United Kingdom
facility: Research Site
city: Stoke on Trent
country: United Kingdom
facility: Research Site
city: Sunderland
country: United Kingdom
facility: Research Site
city: Swansea
country: United Kingdom
facility: Research Site
city: Taunton
country: United Kingdom
facility: Research Site
city: Torquay
country: United Kingdom
facility: Research Site
city: Truro
country: United Kingdom
facility: Research Site
city: Wakefield
country: United Kingdom
facility: Research Site
city: Wigan
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
city: Worcester
country: United Kingdom
facility: Research Site
city: Worthing
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Uppsala University
name: Stefan James
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University
name: Jonas Oldgren
role: STUDY_CHAIR
References: