Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 2

Conditions: Aneurysm

Treatments: Drug: Placebo; Drug: Doxycycline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01756833

R01AG037120 (U.S. NIH Grant/Contract)

HP-00051170

Details and patient eligibility

About

The primary aim of this study is to determine if doxycycline (100 mg bid) will inhibit (by at least 40%) the increase in greatest transverse diameter of small abdominal aortic aneurysms (3.5-5.0 cm in men, 3.5-4.5 cm in women) over a 24-month period of observation in comparison to a placebo-treated control group.

Full description

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.

Enrollment: 261 patients

Sex: All

Ages: 55+ years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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261 participants in 2 patient groups, including a placebo group

Doxycycline

Active Comparator group

Description:

100 mg capsules, twice a day, for a period of two years.

Treatment:

Drug: Doxycycline

Placebo

Placebo Comparator group

Description:

100 mg capsules, twice a day, for a period of two years.

Treatment:

Drug: Placebo