Sodium-glucose cotransporter-2 inhibitors to stabilize coronary ather-osclerosis progression after acute myocardial infarction in women and men with diabetes mellitus

2025-523375-29-00 Therapeutic confirmatory (Phase III) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 9 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Authorised, recruitment pending
Participants planned 300
Countries 1
Sites 9

Myocardial Infarction

To evaluate the effect of SGLT2i on coronary atheroscle-rosis progression on native (untreated) coronary segments in diabetic patients after an AMI treated with successful PCI.

Key facts

Sponsor
Humanitas Mirasole S.p.A.
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2026-02-06
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
AIFA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the effect of SGLT2i on coronary atheroscle-rosis progression on native (untreated) coronary segments in diabetic patients after an AMI treated with successful PCI.

Secondary objectives 5

  1. To assess the correlation between changes in markers of systemic inflammation and coro-nary atherosclerosis progression, based on the hypothesis of SGLT2i-mediated anti-inflammatory effect as a major determinant of their anti-atherosclerotic activity
  2. To perform a prospective evaluation of the adherence to SGLT2i therapy in diabetic women and men, and to report the relative incidence of specific causes for drug discontinuation in both genders
  3. To compare the degree of neointimal hyperplasia on coronary segments which have been treated during primary PCI in patients receiving versus not receiving SGLT2i. Neointimal hyper-plasia will be assessed and quantified by mean of repeat CCTAs
  4. To evaluate the relative decrease in the proportion of high-risk plaque features, as de-scribed using CCTA, at 1 year after AMI in patients who have been treated with SGLT2i
  5. To evaluate the efficacy in terms of improved glycaemic control of adding SGLT2i on top of optimal antidiabetic therapy

Conditions and MedDRA coding

Myocardial Infarction

VersionLevelCodeTermSystem organ class
20.0 PT 10012601 Diabetes mellitus 100000004861
20.0 PT 10000891 Acute myocardial infarction 100000004849

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

  1. Age ≥18 years
  2. Established diagnosis of non-insulin-dependent diabetes mellitus
  3. Hospital admission for AMI (with or without ST-segment elevation); AMI diagnosis should be confirmed with a troponin measurement according to the Fourth Universal Definition of Myocardial Infarction
  4. Successful PCI
  5. Complete revascularization obtained within the index hospitalization
  6. Ability to provide informed consent

Exclusion criteria 9

  1. Known intolerance/contraindications to SGLT2i therapy
  2. Ongoing treatment with SGLT2i at the time of AMI
  3. Contraindications to undergo CCTA
  4. Insulin-dependent diabetes mellitus
  5. Incomplete revascularization with indication to staged PCI on non-culprit lesions
  6. Left ventricular ejection fraction <35% prior to discharge
  7. Known allergy to aspirin or ticagrelor
  8. Known pregnancy
  9. Life expectancy <1 year for non-cardiac conditions

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The primary endpoint will be the change in total coronary percentage atheroma volume (PAV) on native (untreated) segments assessed by coronary CT angiography (CCTA) from baseline to 12 months follow-up. Change in PAV is defined as the difference between PAV at baseline and PAV at 12 months follow-up (PAV change = baseline PAV - 12 months PAV).

Secondary endpoints 1

  1. The secondary endpoints will include: inflammatory biomarkers, biochemical markers of glycaemic control, features of high-risk plaque composition evaluated at CCTA, degree of neointimal hyper-plasia on treated coronary segments at CCTA, adherence to therapy.

Investigational products

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

Test 6

Forxiga 10 mg film-coated tablets

PRD2427550 · Product

Active substance
Dapagliflozin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
3650 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK01 — -
Marketing authorisation
EU/1/12/795/009
MA holder
ASTRAZENECA AB
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Jardiance 10 mg film-coated tablets

PRD1594848 · Product

Active substance
Empagliflozin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
10 mg milligram(s)
Max total dose
3650 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK03 — -
Marketing authorisation
EU/1/14/930/010
MA holder
BOEHRINGER INGELHEIM INTERNATIONAL GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Jardiance 25 mg film-coated tablets

PRD1594891 · Product

Active substance
Empagliflozin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
25 mg milligram(s)
Max total dose
9125 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK03 — -
Marketing authorisation
EU/1/14/930/001
MA holder
BOEHRINGER INGELHEIM INTERNATIONAL GMBH
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Invokana 100 mg film-coated tablets

PRD3349139 · Product

Active substance
Canagliflozin
Substance synonyms
JNJ-28431754, JNJ-28431754-ZAE
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
100 mg milligram(s)
Max total dose
36500 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK02 — -
Marketing authorisation
EU/1/13/884/002
MA holder
JANSSEN-CILAG INTERNATIONAL NV
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Forxiga 5 mg film-coated tablets

PRD3658035 · Product

Active substance
Dapagliflozin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
5 mg milligram(s)
Max total dose
1825 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK01 — -
Marketing authorisation
EU/1/12/795/001
MA holder
ASTRAZENECA AB
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Invokana 300 mg film-coated tablets

PRD3349143 · Product

Active substance
Canagliflozin
Substance synonyms
JNJ-28431754, JNJ-28431754-ZAE
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
300 mg milligram(s)
Max total dose
109500 mg milligram(s)
Max treatment duration
12 Month(s)
Authorisation status
Authorised
ATC code
A10BK02 — -
Marketing authorisation
EU/1/13/884/008
MA holder
JANSSEN-CILAG INTERNATIONAL NV
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Humanitas Mirasole S.p.A.

7 Total trials 3 Recruiting 2 Ended
Academic / Non-commercial
Sponsor organisation
Humanitas Mirasole S.p.A.
Address
Via Alessandro Manzoni 56
City
Rozzano
Postcode
20089
Country
Italy

Scientific contact point

Organisation
Humanitas Mirasole S.p.A.
Contact name
Prof. Giulio Stefanini

Public contact point

Organisation
Humanitas Mirasole S.p.A.
Contact name
Prof. Giulio Stefanini

Locations

1 EU/EEA country · 9 investigational sites

By country

CountryMS statusPlanned subjectsSites
Italy Authorised, recruitment pending 300 9
Rest of world — 0 —

Investigational sites

Italy

9 sites · Authorised, recruitment pending
Humanitas Mirasole S.p.A.
Cardiovascular Department, Via Alessandro Manzoni 56, 20089, Rozzano
Azienda Ospedaliera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
UOC Geriatrics and Internal Medicine, Piazza Luigi Miraglia 2, 80138, Naples
Azienda Ospedaliera Policlinico Universitario Tor Vergata
System Medicine Department, Viale Oxford 81, 00133, Rome
Azienda Ospedaliero Universitaria Pisana
Pathology Department; Cardiothoracic Department, Via Paradisa 2, 56124, Pisa
Ospedale Galeazzi S.p.A.
Division of University Cardiology, Via Cristina Belgioioso 173, 20157, Milan
Azienda Ospedaliero-Universitaria Sant Andre
Division of Cardiology, Via Di Grottarossa 1035-1039, 00189, Rome
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Cardiovascular and Toracic Department, Corso Bramante 88, 10126, Turin
Azienda Ospedaliera Regionale San Carlo
Cardiology, Via Potito Petrone, 85100, Potenza
Ospedale Santa Maria Goretti Latina
UOC UTIC Cardiology, Viale Michelangelo Buonarroti, 04100, Latina

Results and documents

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

Documents 16 files

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

TypeTitleVersion
Protocol (for publication) D1_ Protocol 2025-523375-29-00 3.0
Protocol (for publication) D4_Patient facing document_diary form 1.0
Recruitment arrangements (for publication) K1_Recruitment arrangements 1
Subject information and informed consent form (for publication) L1_SIS and ICF adults altri centri 2
Subject information and informed consent form (for publication) L1_SIS and ICF adults altri centri V2 21Dec2025_tc 2
Subject information and informed consent form (for publication) L1_SIS and ICF adults IRCCS Humanitas 2
Subject information and informed consent form (for publication) L1_SIS and ICF adults IRCCS Humanitas V2 21Dec2025_tc 2
Subject information and informed consent form (for publication) L2_Other subject information material_GPLetter altri centri 1
Subject information and informed consent form (for publication) L2_Other subject information material_GPLetter IRCCS Humanitas 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Forxiga 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Forxiga 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Invokana 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Invokana 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Jardiance 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Jardiance 1
Synopsis of the protocol (for publication) D1_ Protocol synopsis_IT 2025-523375-29-00 3.0

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-10-17 Italy Acceptable
2026-02-02
 2026-02-06
2 SUBSTANTIAL MODIFICATION SM-2 2026-02-27 Italy Acceptable 2026-03-16

Related clinical trials