Metformin for AAA Growth Inhibition: A randomized controlled trial

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 100

Inclusion Criteria

Provision of written informed consent.
Male and female patients.
Age 50-80 years.
Documented AAA Ø 30-49 mm for men and 30-44 mm for women.
Fasting p-glucose <7.0 mmol/L (WHO 1999). 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:
- Renal failure with glomerular filtration rate (GFR) <45ml/min according to
the revised Lund-Malmo* formula.
- Hypersensitivity to metformin or any of the excipients included in the
tablet.
- Acute metabolic acidosis.
- Diabetic pre-coma.
- Acute conditions with the potential to alter renal function such as;
dehydration, severe infection or shock.
- Acute or chronic disease which may cause tissue hypoxia such as;
decompensated heart failure, respiratory failure, recent myocardial infarction
or shock.
- 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.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To examine if up to 2g metformin administered daily over a five-year period<br /><br>reduces AAA growth as measured by computed tomography (CT) imaging of AAA<br /><br>diameter in patients with small AAAs who do not have diabetes. An interim<br /><br>STOP/GO analysis will be performed after two-years of treatment. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary objectives<br /><br>To examine if metformin limits increase in; a) CT-assessed AAA volume; b)<br /><br>ultrasound assessed AAA diameter; c) improves health-related quality of life;<br /><br>d) reduces the need for surgery (diameter >=55mm) or rupture; and e) represents<br /><br>a cost-effective treatment to reduce the need for AAA surgery.<br /><br><br /><br>Exploratory objectives<br /><br>To examine; a) if there is a dose or time related response of metformin<br /><br>regarding the primary or secondary endpoints; and b) if metformin favorably<br /><br>modifies circulating inflammation and matrix remodeling biomarkers; or c)<br /><br>affects perivascular adipose tissue.<br /><br><br /><br>Safety objective<br /><br>To determine adverse events; primarily related to known side effects of<br /><br>metformin and possible unexpected effects on AAA, related to metformin<br /><br>treatment after two and five years.</p><br>