METFORMIN EMBONATE for Small abdominal aortic aneurysm (AAA)

Inclusion criteria

• {"criterion_text":"- Provision of written informed consent\n- Male and female patients\n- Age 50-80 years\n- Documented AAA Ø 30-49 mm for men and 30-44 mm for women\n- No history of diabetes mellitus and fasting p-glucose <7.0 mmol/L"}

Exclusion criteria

• {"criterion_text":"- Short expected survival.\n- History of current or previous diabetes mellitus.\n- Current or previous use of metformin.\n- Not expected to tolerate metformin.\n- Contraindications to metformin treatment according to SmPC: a) Renal failure with glomerular filtration rate (GFR) <45ml/min according to the revised Lund-Malmö formula. b) Hypersenisitivity to metformin or any of the excipients included in the tablet. c) Acute metabolic acidosis. d) Diabetic pre-coma. e) Acute conditions with the potential to alter renal function such as; dehydration, severe infection or shock. f) Acute or chronic disease which may cause tissue hypoxia such as; decompensated heart failure, respiratory failure, recent myocardial infarction or shock. g) Hepatic insufficiency, acute alcohol intoxication, alcoholism.\n- Known or suspected connective tissue disorder (Marfans syndrome, etc), infected or inflammatory aneurysm, aneurysm development after aortic dissection or previous surgery of the infrarenal aorta.\n- Enrolment in either another investigational drug or medical device study or another investigational study of an approved drug or medical device within 30 days prior to enrolment of the current study.\n- If, in the opinion of the investigator, it is not in the patient's medical interest to participate in the study or the patient is unlikely to be able to comply with the study protocol.\n- Pregnancy. Women of childbearing potential are only included after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test as well as willingness to comply with highly effective anti-contraception throughout the study period"}

Primary endpoints

• {"endpoint_text":"- To examine if 2 g metformin administered daily over a five-year period slows AAA growth rate in patients with small AAAs who do not have diabetes mellitus measured as computed tomography (CT) imaging assessed AAA diameter. Measured at baseline versus 24 and 60 months of treatment.","definition_or_measurement_approach":"Computed tomography (CT) imaging assessed AAA diameter; measurements compared baseline vs 24 months and 60 months of treatment."}

Secondary endpoints

• {"endpoint_text":"- To examine if metformin; a) limits increase in CT-assessed AAA volume; b) ultrasound assessed AAA diameter; c) improve health-related quality of life; and d) represent a cost-effective treatment to reduce the need for AAA surgery.","definition_or_measurement_approach":"a) CT-assessed AAA volume change; b) ultrasound-assessed AAA diameter; c) validated health-related quality of life instruments; d) health economic/cost-effectiveness analyses to assess reduction in need for AAA surgery."}
• {"endpoint_text":"- Safety objective. To determine adverse events; primarily related to known side effects of metformin and possible unexpected effects on AAA, related to metformin treatment after two and five years treatment.","definition_or_measurement_approach":"Adverse events collection and safety monitoring at 24 months and 60 months, focusing on known metformin side effects and potential unexpected AAA-related effects."}
• {"endpoint_text":"- Exploratory objectives. To examine; a) if there is a dose or time related response of metformin regarding the primary or secondary endpoints; and b) if metformin favorably modify circulating inflammation and matrix remodeling biomarkers; or c) affect perivascular adipose tissue.","definition_or_measurement_approach":"Exploratory analyses of dose/time-response relationships; measurement of circulating inflammation and matrix remodeling biomarkers; imaging/biologic assessment of perivascular adipose tissue."}

Sweden

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

8

Number Of Sites

10

Number Of Participants

400

Denmark

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

15-11-2024

Processing Time Days

11

Number Of Sites

1

Number Of Participants

50

Netherlands

Earliest CTIS Part Ii Submission Date

04-11-2024

Latest Decision Or Authorization Date

11-11-2024

Processing Time Days

7

Number Of Sites

1

Number Of Participants

50

Primary sponsor

Full Name

Uppsala University

Organisation Type

Educational Institution

Country Of Registered Address

Sweden

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}