Dapagliflozin effects on cardiometabolic outcomes in patients with an acute heart attack. - DAPA-MI

Study identifier:D169DC00001

ClinicalTrials.gov identifier:NCT04564742

EudraCT identifier:2020-000664-31

CTIS identifier:N/A

Study Complete

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

Medical condition

Acute Myocardial Infarction

Phase

Phase 3

Healthy volunteers

Study drug

Dapagliflozin, Placebo

Sex

All

Actual Enrollment

4017

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 22 Dec 2020

Primary Completion Date: 05 Jul 2023

Study Completion Date: 05 Jul 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2025 by AstraZeneca

Collaborators

Uppsala Clinical Research Center

Inclusion and exclusion 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)

Location

Research Site

Sheffield, United Kingdom, S5 7AU

Location

Research Site

Blackpool, United Kingdom, FY3 8NR

Location

Research Site

Leicester, United Kingdom, LE3 9QP

Location

Research Site

Bradford, United Kingdom, BD9 6RJ

Location

Research Site

Hull, United Kingdom, HU16 5JQ

Location

Research Site

Newcastle upon Tyne, United Kingdom, NE7 7DN

Location

Research Site

Headington, United Kingdom, OX3 9DU

Location

Research Site

Wolverhampton, United Kingdom, WV10 0QP

Arms	Assigned Interventions
Experimental: Dapagliflozin Patients will be randomized 1:1 to either dapagliflozin or placebo	Drug: Dapagliflozin Dapagliflozin 10 mg tablets given once daily, per oral use Other Name: Forxiga TM Other Name: Farxiga TM
Placebo Comparator: Placebo Placebo matching dapagliflozin	Drug: Placebo Placebo matching dapagliflozin 10 mg tablets given once daily, per oral use

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Dapa 10 mg	Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily
Placebo	Control, Green, plain, diamond shaped, film coated tablets, once daily

Participant Flow: Overall Study

	Dapa 10 mg	Placebo
STARTED	2019	1998
COMPLETED	2014	1994
NOT COMPLETED	5	4
Lost to Follow-up	1	0
Consent Withdrawal	4	4

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Dapa 10 mg	Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily
Placebo	Control, Green, plain, diamond shaped, film coated tablets, once daily

Baseline Measures

	Dapa 10 mg	Placebo	Total
Number of Participants [units: Participants]	2019	1998	4017
Sex: Female, Male [units: Participants]
Female	388	419	807
Male	1631	1579	3210
Race/Ethnicity, Customized [units: Participants]
American Indian or Alaska Native	0	0	0
Asian	64	52	116
Black or African American	8	15	23
Native Hawaiian or other Pacific Islander	0	0	0
Other	40	37	77
White	1905	1893	3798
MISSING	2	1	3
Age, Customized [units: Participants]
>65 years	831	799	1630
<=65 years	1188	1199	2387
Age Continuous [units: Years] Mean ± Standard Deviation Age (Years)	63.0 ± 11.06	62.8 ± 10.64	62.9 ± 10.85

Outcome Measures

1. Primary Outcome Measure: Analysis of the hierarchical primary composite endpoint (full analysis set) [ Time Frame: 29 months ]

Measure Type	Primary
Measure Name	Analysis of the hierarchical primary composite endpoint (full analysis set)
Measure Description	Study participants received dapagliflozin 10 mg or matching placebo, given once daily in addition to SoC. Overall, the mean study duration was 12.0 months (time in study until last visit) with an accumulated 4023.9 participant-years. The maximum study duration for any participant was 29 months. "Number of Events" for NYHA corresponds to the number of participants with a non-missing value for NYHA functional class at the last visit, and that all participants with a non-missing value take part in the analysis comparing their NYHA class value with all other participants with a NYHA value, according to the win-ratio method.
Time Frame	29 months
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All participants are included in the analysis; Each row item displays the number of participants for the given event, and without preceding events defined in the hierarchical order.

Reporting Groups

	Description
Dapa 10 mg	Active, Green, plain, diamond shaped, film coated tablet, 10 mg once daily
Placebo	Control, Green, plain, diamond shaped, film coated tablets, once daily

Measured Values

	Dapa 10 mg	Placebo
Number of Participants Analyzed [units:participants]	2019	1998
Analysis of the hierarchical primary composite endpoint (full analysis set) [units: Participants]
The hierachical composite endpoint of all components	1990	1970
Death, adjudicated	41	33
Hospitalisation due to HF	32	41
Non-fatal MI	29	32
AF/Flutter event	8	15
New onset of T2DM	40	74
NYHA Classification at last visit, measuring limitations of physical activity	1839	1773
Body Weight decrease of at least 5% at last visit	684	468

Statistical Analysis 1 for Analysis of the hierarchical primary composite endpoint (full analysis set)

Groups^[1]	All groups
Method^[3]	Other [Win Ratio Analysis]
P-Value^[4]	<0.001
Other^[5]	1.34
95% Confidence Interval	( 1.20 to 1.50 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The primary objective of the study was to determine if the clinical benefit of dapagliflozin was superior as compared with placebo, utilizing a hierarchical composite endpoint and win-ratio (WR) method. With a presumed WR of 1.20, 4000 patients were provide an 80% statistical power for the primary endpoint, maintaining a 1:1 allocation between treatments. The primary analysis was based on the intention-to-treat principle using the Full Analysis Set.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	A closed testing procedure including a pre-specified hierarchical ordering of the primary and secondary endpoints was utilised. No multiplicity control was placed on the exploratory endpoints.
[5]	Other relevant estimation information:
	No text entered.

Serious Adverse Events

Time Frame	Time frame was from date of randomization and up to and including last day in study, up to 29 months.
Additional Description	No text entered.

Reporting Groups

	Description
Dapa 10 mg	Description (Arm-group)
Placebo	Description (Arm-group)