Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial

N-TA^3CT is a randomized, double-blind, placebo-controlled test of the hypothesis that
doxycycline 100 mg bid, will reduce the rate of increase of maximum transverse diameter of
small (3.5-5.0 cm among men and 3.5 to 4.5 cm among women) abdominal aortic aneurysms. The
primary outcome is abdominal aortic aneurysm (AAA) maximum transverse diameter determined by
CT scans at two-year follow-up with allowance for baseline (pre-randomization) diameter.
Based on an anticipated growth rate of 2.5 mm per year in the placebo group and the current
threshold at which surgical intervention will be offered to trial participants, (5.5 cm in
men, 5.0 cm in women), the upper limit of AAA size for inclusion has been set at 5.0 cm for
men and 4.5 cm for women. Among these subjects, the threshold for repair would be exceeded
only by those exhibiting persistent growth. Secondary outcomes will determine if doxycycline
affects other measures, e.g., MMP-9 levels in plasma and whether these effects are related to
aneurysm growth. Nineteen clinical sites have identified pools of over 1600 patients with
small aneurysm who meet the proposed inclusion/exclusion criteria. Two hundred fifty-eight
patients will be randomized to placebo or doxycycline and their aneurysms followed for change
in diameter at six-month intervals using CT imaging. The alternative hypothesis is that
doxycycline will inhibit the expansion rate by 40% during the two years of observation.
Patients enrolling in N-TA^3CT must be able to give consent for their participation
themselves and meet study eligibility criteria.

Inclusion Criteria:

- Patients 55 years of age or older, women post-surgical menopause or at least two years
since last menses if natural menopause.

- CT scan documented infrarenal abdominal aortic aneurysm with maximum transverse
diameter larger than 35 mm and no greater than 50 mm, in men, and larger than 35 mm
and no greater than 45 mm in women.

Exclusion Criteria:

- Patients will be excluded from the study if they are unable to give their own informed
consent to participate.

- have symptoms related to abdominal aortic aneurysm.

- have other intra-abdominal vascular pathology that may require repair within 24 months
(e.g., renal artery stenosis, large iliac artery aneurysms, iliac occlusive disease,
aneurysmal involvement of the renal artery).

- have had previous abdominal aortic aneurysm repair by open surgical or endovascular
technique.

- have an active malignancy with life expectancy less than two years.

- have an allergy to tetracycline.

- are currently or have been recently treated (previous six months) with tetracycline
derivatives.

- they are currently taking anti-seizure medicines metabolized by pathways influenced by
doxycycline (e.g., carbamazepine, phenytoin, and barbiturates).

- stage II hypertension (patients whose blood pressure is persistently in the range of
systolic > 160 mm Hg or diastolic > 100 mm Hg despite primary physician's best effort
to achieve adequate therapy.

- have dialysis dependent renal failure or impending dialysis treatment for renal
insufficiency.

- have a chronic infection requiring long-term (> 2 weeks) antibiotics.

- have known genetic syndromes responsible for the abdominal aortic aneurysm (e.g.,
Marfan's Syndrome).

- are under treatment with systemic immunosuppressive agents.

- could become pregnant.

- are not good candidates for clinical trial participation.

- are enrolled in another clinical trial.