DAPAgliflozine to attenuate cardiac RemOdeling afTEr aCuTe myOcardial infarction

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

19 Nov 2024 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511882-13-01

EudraCT number

2022-001901-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Assess the efficacy of dapagliflozin, in addition to standard recommended therapy compared to standard recommended therapy alone (i.e. with placebo) on cardiac systolic function and remodeling at 6 months from randomization by transthoracic echocardiography (TTE), in AMI patients with LV dysfunction.

Secondary objectives 1

1. assess the efficacy and safety of dapagliflozin compared to placebo in addition to optimal secondary prevention in the prevention of cardiac dysfunction after AMI with LV dysfunction, using changes in several parameters assessed from baseline to Month 6 (+4 weeks) including pulmonary congestion by TTE, clinical outcomes, biomarkers and severe complications related to dapagliflozin. In addition, cardiac remodeling will assessed by TTE using changes in cardiac volumes and strain

Conditions and MedDRA coding

Cardiac failure

Regulatory references

Plan to share IPD

Yes

IPD plan description

All of the individual participant data collected during the trial, subject to compliance to regulations, will be available. Document (Study protocol, statistical analysis plan, informed consent form, clinical study report, analytic code) will be also available. Data will be available immediately following publication ending 2 years after publication, with investigators whose proposed use of the data has been approved by the PI and / or the review commitee if relevant. Proposals should be directed to [email protected]. To gain access, data requestors will need to sign a data access agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 years
2. STEMI (e.g., ST elevation above the J-point of ≥0.1 millivolt in ≥two contiguous leads or left bundle branch block) or very high-risk NSTEMI (e.g., dynamic ECG changes or ongoing chest pain or acute heart failure or hemodynamic instability independent of ECG changes or life-threatening ventricular arrhythmias) with LV dysfunction (LVEF ≤45%); after completion of PCI or angiography procedure
3. eGFR ≥25 mL/Min per 1.73m²
4. Systolic blood pressure (SBP) before first dosing >100 mmHg and/or Diastolic blood pressure (DBP) >70 mmHg before first dosing
5. Ability to provide written informed consent and willing to participate in the 6-month follow-up period.
6. Affiliation to a national health care system (AME are not allowed).

Exclusion criteria 18

1. Cardiogenic shock (SBP <90 mmHg with clinical signs of low output or patients requiring inotropic agents) at randomization
2. Impossibility to evaluate cardiac remodeling using TTE (e.g., pacemaker or defibrillator …)
3. Atrial fibrillation rhythm at randomization
4. Life expectancy <6 month
5. Known pregnancy at time of randomization
6. Breastfeeding women
7. Females of childbearing potential without adequate contraceptive methods (i.e. sterilization, intrauterine device, vasectomized partner; or medical history of hysterectomy)
8. Current participation in another interventional trial
9. Patients under guardianship or curatorship
10. Referred to surgery for coronary artery bypass grafting (CABG) or treatment of acute complications (e.g. ventricular septal rupture)
11. Any other form of diabetes than diabetes type 2
12. History of diabetic ketoacidosis (DKA)
13. Known contra-indication to SGLT-2 inhibitors (hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption)
14. >1 episode of severe hypoglycemia within the last 6 months under treatment with insulin or sulfonylurea
15. Acute symptomatic urinary tract infection (UTI) or genital infection at the time of randomization
16. Concomitant long-term treatment (and/or within the 4 weeks prior to the baseline visit) with any SGLT-2 inhibitor (dapagliflozin, canagliflozin, empagliflozin)
17. Echocardiographic examination of insufficient quality to permit adequate analysis of the study end-points.
18. Patients with a known hypersensitivity to dapagliflozin or any of the excipients of the product.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Two primary endpoints will allow to evaluate two independent and potent predictors of mortality after AMI: 1)Cardiac systolic function, assessed by change in left ventricular ejection fraction (LVEF) from baseline to Month 6) (+4 weeks) by TTE
2. 2) Remodeling, assessed by change in left atrium volume (LAV) from baseline to Month 6 ) (+4 weeks) by TTE

Secondary endpoints 4

1. Secondary endpoints: comparison in each group from baseline to Month 6 (+ 4 weeks) using TTE - Change in left ventricular end-systolic volume (LVESV) - Change in left ventricular end-diastolic volume (LVEDV) - Change in LV global longitudinal strain (LS) - Change in left atrial strain (LAS)
2. Secondary endpoints: comparison between both groups (experimental vs. placebo) - Duration of hospital stay (index hospitalization) - All-cause mortality at 6-months - Cardiovascular death or worsening HF at 6-months - Number of re-admission due to HF at 6-months
3. Change from baseline to Month 6 (+ 4 weeks) in LVESV, LVEDV, LAV, LVEF, LV global LS, LAS and pulmonary congestion (normal lung, mild, moderate or severe ultrasound lung comets [ULCs]) using TTE at month 6 - Change from baseline to Month 6 (+ 4 weeks) in plasma levels of NT-pro BNP and HBA1C - Change in body weight from baseline to Month 6 (+4 weeks)
4. Adverse events, with particular focus to those potentially related to dapagliflozin complications (e.g., all symptoms of volume depletion, major hypoglycemia, genital infections, diabetes ketoacidosis, changes in liver function parameters [ASAT, ALAT ≥3 USN], changes in renal function parameters [creatine x2, eGFR <30 mL/Min per 1.73m²]), fractures, and lower limb amputations) at Month 6)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Coordinating Investigator

Locations

1 EU/EEA country · 32 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications