Clinical trial NCT04224051: Metformin for Abdominal Aortic Aneurysm Growth Inhibition
Official title: Metformin for AAA Growth Inhibition, a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE2
Conditions: Abdominal Aortic Aneurysm
Lead sponsor: Uppsala University Hospital
Sponsor class: OTHER
First posted: 2020-01-13
Enrollment: 500
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A multi-centre population-based open-label randomized controlled trial with allocation concealment and blinded outcome assessment will examine if up to 2g metformin daily slows AAA growth in patients with small AAAs who do not have diabetes.

Detailed description: Subjects with no history of diabetes will be recruited from a cohort of patients with diagnosed AAA and a maximum aortic diameter of 30-49mm for men and 30-44mm for women.

A total of 500 subjects with AAA will be included in the study, 250 in each study arm. Patients will be randomised to metformin or standard care in a 1:1 ratio.

CT imaging and AAA US will be performed at baseline, 24 months and end of study, as well as if necessary according to clinical routine. Study drug will start at baseline and continue through completion.

When all enrolled subjects have completed the 24-month follow-up (including imaging) an interim analysis will be performed to assess for efficacy and safety; if there is no trend towards a positive effect or signs of a harmful effect of metformin, the study will be stopped at this phase.

Eligibility criteria: Inclusion Criteria:

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. Fasting p-glucose \<7.0 mmol/L. Fasting is defined as no caloric intake for ≥8 h.

Exclusion Criteria:

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
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. Enrollment 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 enrollment 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.

Primary outcomes:
measure: Abdominal aortic aneurysm (AAA) diameter growth rate
timeFrame: 5 years
Secondary outcomes:
measure: Abdominal aortic aneurysm (AAA) volume growth rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
state: Sverige
Study officials:
affiliation: Uppsala University Hospital
name: Jon Unosson, PhD
role: PRINCIPAL_INVESTIGATOR
References: