Impact of Oral Semaglutide on Platelet Reactivity in Patients with Diabetes Mellitus or Overweight with High Risk or established Cardiovascular Disease: the SEMA-PLAT Study

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

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Authorised, recruitment pending

Participants planned 212

Countries 1

Sites 1

Diabetes Mellitus

Key facts

Sponsor: Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Nutritional and Metabolic Diseases [C18]
Decision date (initial): 2026-04-23
Transition trial: No
Low-intervention: Yes
Rare-disease indication: No
Vulnerable population: No
Funding sources: Università La Sapienza - Roma

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response

Cohort 1:
To explore the effects of different doses of oral semaglutide versus control on platelet reactivity in type 2 diabetic patients with an indication to GLP-1 RA undergoing aspirin or aspirin + clopidogrel.
Cohort 2:
To explore the effects of different doses of subcutaneous semaglutide versus control on platelet reactivity in obese (BMI≥30 kg/m2) or overweight (BMI≥27 kg/m2) non-diabetic patients with at least one weight-related comorbidity or established CV disease, undergoing aspirin or aspirin + clopidogrel.

Secondary objectives 2

Cohort 1: • Secondary Objective: To explore the effects of different doses of oral semaglutide versus control on markers of thrombus formation, inflammation, oxidative stress, endothelial function and autophagy in type 2 diabetic patients with an indication to GLP-1 RA undergoing aspirin or aspirin + clopidogrel.
Cohort 2: • Secondary Objective: To explore the effects of different doses of subcutaneous semaglutide versus control on markers of thrombus formation, inflammation, oxidative stress, endothelial function, and autophagy in obese (BMI≥30 kg/m2) or overweight (BMI≥27 kg/m2) non-diabetic patients with at least one weight-related comorbidity or established CV disease, undergoing aspirin or aspirin + clopidogrel.

Conditions and MedDRA coding

Diabetes Mellitus

Version	Level	Code	Term	System organ class
28.0	PT	10067585	Type 2 diabetes mellitus	100000004861
20.0	SOC	10007541	Cardiac disorders	11
24.1	PT	10033307	Overweight	100000004861
20.0	PT	10029883	Obesity	100000004861

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

Cohort 1: Type 2 Diabetes mellitus AND an indication for GLP-1 RA treatment as per the ESC guidelines. Cohort 2: BMI≥30kg/m2 OR BMI≥27 kg/m2 non-diabetic patients AND an indication for GLP-1 RA treatment as per the ESC guidelines, including patients with the presence of at least one weight-related comorbidities (hypertension, dyslipidemia, obstructive sleep apnea), OR established CV disease, defined as prior MI, stroke (ischemic and hemorrhagic stroke), or symptomatic PAD (as evidenced by intermittent claudication with ankle–brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease).
On treatment with aspirin (81-100 mg/od) alone or aspirin (81-100 mg/od) plus clopidogrel (75mg/od) as per standard of care since at least 14 days before enrolment;
Male or female aged >45 and <75 years;
Are willing to be consented and to understand the study requirements, to adhere to study treatments, and complete all assessments and all scheduled visits, per Investigator judgment.
All women of childbearing potential must agree to use highly effective contraception from the time of informed consent until at least 8 weeks after the last dose of the investigational medicinal product.
Blood tests not older than 2 months including hemoglobin (Hb), estimated glomerular filtration rate (eGFR), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

Exclusion criteria 17

Myocardial infarction, stroke, hospitalization for unstable angina pectoris, transient ischemic attack or other arterial or venous thrombosis within the past 90 days prior to the day of screening
On treatment with anticoagulant agents or with antiplatelets other than aspirin or aspirin and clopidogrel
Use of any DPP-4 inhibitor, any GLP-1 RA or pramlintide within 30 days prior to screening
Known or suspected hypersensitivity to semaglutide or related products;
Concomitant or expected chronic use of steroids or non-steroidal anti-inflammatory drugs;
Patient has a diagnosis of type 1 DM, or a history of ketoacidosis
Presence of severe heart failure – systolic or diastolic NYHA Class 4;
Presence of end stage renal impairment defined as eGFR <15ml/min, chronic or intermittent hemodialysis or peritoneal dialysis
Known severe liver disease
History or presence of acute or chronic pancreatitis
History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g., subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
Proliferative retinopathy or maculopathy requiring acute treatment
Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy in the previous 5 years
Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
Currently enrolled in a competing randomized trial or less than 30 days since ending another trial with an investigational product or device
Presence of medical conditions that would make the patient unlikely to compliant with study related procedures
Women who are pregnant, breast feeding or may be considering pregnancy during the study period

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

Change in platelet reactivity assessed by light transmission aggregometry [LTA] following ADP (2 and 5 μmol/L) and collagen (2 μg/mL) stimuli between groups at T3;

Secondary endpoints 1

Changes between groups at different time points (T1, T2 and T3) in: • Markers of thrombus formation (T-TAS AUC, P-selectin, aGPIIbIIIa, PDMP) • Inflammatory markers (IL-1, IL-6); • Oxidative stress markers (H₂O₂, sNOX2-dp, HBA); • Endothelial function markers (NO, endothelin-1); • Autophagy markers (p62, LC3, ATG5).

Investigational products

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

Test 8

Rybelsus 14 mg tablets

PRD7996062 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 14 mg milligram(s)
Max total dose: 630 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/008
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Wegovy 1.7 mg solution for injection in pre-filled pen

PRD9446838 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS INJECTION
Max daily dose: 1.7 mg milligram(s)
Max total dose: 76.5 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/21/1608/004
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rybelsus 3 mg tablets

PRD7996055 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 3.00 mg milligram(s)
Max total dose: 135 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/001
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Wegovy 1 mg solution for injection in pre-filled pen

PRD9446837 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS INJECTION
Max daily dose: 1.00 mg milligram(s)
Max total dose: 45.00 mg milligram(s)
Max treatment duration: 45 Week(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/21/1608/003
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Wegovy 0.25 mg solution for injection in pre-filled pen

PRD9446835 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS INJECTION
Max daily dose: 0.25 mg milligram(s)
Max total dose: 11.25 mg/g milligram(s)/gram
Max treatment duration: 45 Month(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/21/1608/001
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Rybelsus 7 mg tablets

PRD7996059 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: TABLET
Route of administration: ORAL USE
Max daily dose: 7 mg milligram(s)
Max total dose: 315 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/20/1430/005
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Wegovy 2.4 mg solution for injection in pre-filled pen

PRD9446839 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS INJECTION
Max daily dose: 2.40 mg milligram(s)
Max total dose: 108 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/21/1608/005
MA holder: NOVO NORDISK A/S
MA country: EU
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Wegovy 0.5 mg solution for injection in pre-filled pen

PRD9446846 · Product

Active substance: Semaglutide
Substance synonyms: NNC0113-0217
Pharmaceutical form: SOLUTION FOR INJECTION
Route of administration: SUBCUTANEOUS INJECTION
Max daily dose: 0.50 mg milligram(s)
Max total dose: 22.50 mg milligram(s)
Max treatment duration: 45 Day(s)
Authorisation status: Authorised
ATC code: A10BJ06 — -
Marketing authorisation: EU/1/21/1608/002
MA holder: NOVO NORDISK A/S
MA country: Norway
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Comparator 2

Clopidogrel Medreg 75 mg filmom obalené tablety

PRD10022665 · Product

Active substance: Clopidogrel
Pharmaceutical form: FILM-COATED TABLET
Route of administration: ORAL
Max daily dose: 75 mg milligram(s)
Max total dose: 15375 mg milligram(s)
Max treatment duration: 205 Day(s)
Authorisation status: Authorised
ATC code: B01AC04 — CLOPIDOGREL
Marketing authorisation: 16/0261/22-S
MA holder: MEDREG S.R.O.
MA country: Slovakia
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Acetylsalicylic acid Krka 100 mg enterotabletter

PRD4747549 · Product

Active substance: Acetylsalicylic Acid
Pharmaceutical form: GASTRO-RESISTANT TABLET
Route of administration: ORAL
Max daily dose: 100 mg milligram(s)
Max total dose: 20500 mg milligram(s)
Max treatment duration: 205 Month(s)
Authorisation status: Authorised
ATC code: B01AC06 — ACETYLSALICYLIC ACID
Marketing authorisation: 54356
MA holder: KRKA, D.D., NOVO MESTO
MA country: Sweden
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali

Sponsor organisation: Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali
Address: Via Franco Faggiana 1668
City: Latina
Postcode: 04100
Country: Italy

Scientific contact point

Organisation: Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali
Contact name: Mattia Galli

Public contact point

Organisation: Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali
Contact name: Mattia Galli

Locations

1 EU/EEA country · 1 investigational sites

By country

Country	MS status	Planned subjects	Sites
Italy	Authorised, recruitment pending	212	1
Rest of world	—	0	—

Investigational sites

Italy

1 site · Authorised, recruitment pending

Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali

Cardiology, Via Franco Faggiana 1668, 04100, Latina

Results and documents

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

Documents 23 files

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

Type	Title	Version
Protocol (for publication)	D1_Protocol_2025-522486-29-01_ V2_03March2026_tc_redacted	3
Protocol (for publication)	D1_Protocol_2025-522486-29-01_redacted	3
Recruitment arrangements (for publication)	K1_Recruitment arrangements_2025-522486-29-01	3
Recruitment arrangements (for publication)	K1_Recruitment arrangements_2025-522486-29-01_TC	3
Subject information and informed consent form (for publication)	L1_Informativa e consenso trattamento dei dati personali_V1_18112025_2025-522486-29-01	1
Subject information and informed consent form (for publication)	L1_SIS and ICF adult_Coorte1_2025-522486-29-01	3
Subject information and informed consent form (for publication)	L1_SIS and ICF adult_Coorte1_2025-522486-29-01_V2_TC	3
Subject information and informed consent form (for publication)	L1_SIS and ICF adult_Coorte2_2025-522486-29-01	3
Subject information and informed consent form (for publication)	L1_SIS and ICF adult_Coorte2_2025-522486-29-01_V2_TC	3
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	BLANK	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_ASA_100mg_2025-522486-29-01	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_Clopidogrel_75mg_2025-522486-29-01	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_Rybelsus_2025-522486-29-01	1
Summary of Product Characteristics (SmPC) (for publication)	G2_SmPC_Wegovy_2025-522486-29-01	1
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ENG_2025-522486-29-01_redacted	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ENG_2025-522486-29-01_V2_03March2026_tc_redacted	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ITA_2025-522486-29-01_redacted	3
Synopsis of the protocol (for publication)	D1_Protocol Synopsis_ITA_2025-522486-29-01_V2_03March2026_tc_redacted	3

Application history

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

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2025-12-24	Italy	Acceptable 2026-04-22	2026-04-23

Impact of Oral Semaglutide on Platelet Reactivity in Patients with Diabetes Mellitus or Overweight with High Risk or established Cardiovascular Disease: the SEMA-PLAT Study

Overview

Key facts

Trial design

Main objective

Secondary objectives 2

Conditions and MedDRA coding

Eligibility criteria

Inclusion criteria 6

Exclusion criteria 17

Endpoints

Primary endpoints 1

Secondary endpoints 1

Investigational products

Test 8

Comparator 2

Sponsors and contacts

Casa Di Cura Accreditata Istituto Chirurgico Ortopedico Traumatologico Marco Pasquali

Scientific contact point

Public contact point

Locations

By country

Investigational sites

Results and documents

Documents 23 files

Application history

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