Does metformin reduce growth rate of small abdominal aortic aneurysms?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uppsala University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

12 Dec 2019 → ongoing

Decision date (initial)

2024-11-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Uppsala University, Department of Surgical Sciences

External identifiers

EU CT number

2024-517387-37-00

EudraCT number

2018-004289-33

ClinicalTrials.gov

NCT04224051

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To investigate if 2 g metformin daily over 60 months reduce yearly growth rate of small abdominal aortic aneurysms in patients with no
history of diabetes.
At 24 months a Stop/Go interim analysis will be performed for safety and efficacy.

Secondary objectives 1

1. To investigate if metformin 2 g per day is tolerable and safe, affects quality of life, affects biomarkers associated with aortic aneurysms and may represent a cost effective medical treatment in patients with a small abdominal aortic aneurysm and no history diabetes.

Conditions and MedDRA coding

Small abdominal aortic aneurysm (AAA) under active surveillance; 30-49 mm in diameter for men and 30-44 mm in diameter for women

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Provision of written informed consent
2. Male and female patients
3. Age 50-80 years
4. Documented AAA Ø 30-49 mm for men and 30-44 mm for women
5. No history of diabetes mellitus and fasting p-glucose <7.0 mmol/L

Exclusion criteria 9

1. Short expected survival.
2. History of current or previous diabetes mellitus.
3. Current or previous use of metformin.
4. Not expected to tolerate metformin.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 3

1. 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.
2. 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.
3. 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.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uppsala University

Sponsor organisation

Uppsala University

Address

Box 256

City

Uppsala

Postcode

751 05

Country

Sweden

Scientific contact point

Organisation

Uppsala University

Contact name

Department of Surgical Sciences

Public contact point

Organisation

Uppsala University

Contact name

Department of Surgical Sciences

Third parties 1

Locations

3 EU/EEA countries · 12 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 12 files

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

Application history

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