Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 261
- 试验地点
- 22
- 主要终点
- Difference in Z-score for Rank of Maximum Transverse Diameter (MTD) Regressed on Z-score at Baseline to Assess Growth in Abdominal Aortic Aneurysm MTD Determined by CT Scans at Two-year Follow-up and Baseline (Pre-randomization).
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Doxycycline
100 mg capsules, twice a day, for a period of two years.
干预措施: Doxycycline (Drug)
Placebo
100 mg capsules, twice a day, for a period of two years.
干预措施: Placebo (Drug)
结局指标
主要结局
Difference in Z-score for Rank of Maximum Transverse Diameter (MTD) Regressed on Z-score at Baseline to Assess Growth in Abdominal Aortic Aneurysm MTD Determined by CT Scans at Two-year Follow-up and Baseline (Pre-randomization).
时间窗: Baseline and two years from randomization (when patients were late in returning for visits, their data were used up to three years).
Diameters were ranked from smallest to largest. Worse ranks were assigned to surviving patients who underwent aneurysm repair (in order of longest to shortest time from randomization to repair), and worst ranks were assigned to patients who died (in order likewise). Each rank was converted to a z-score corresponding to the value on the standard normal curve of its percentile. The primary analysis was based on linear regression of the change in z-scores from baseline to 2 years. Independent variables were baseline z-score, sex, and a dichotomous variable for the randomly assigned treatment group (0 for placebo, 1 for doxycycline). Missing values were multiply imputed. Higher score corresponds to less favorable outcome. There is no scale associated with these z-scores; the absolute z-scores have no biological meaning or clinically relevant threshold. A z-score of 0 corresponds to the median rank. The maximum and minimum z-scores are +2.41 and -2.41. See References in Protocol Section.
次要结局
- Maximum Transverse Diameter, cm(Six months, one year, and two years (when patients were late in returning for visits their data were used up to three years).)
- Volume, cm^3(Six months, one year, and two years (when patients were late in returning for visits their data were used up to three years).)
- MMP-9, ng/ml(Six months, one year, 18 months, and two years (when patients were late in returning for visits their data were used up to three years).)
- CRP, mg/l(Six months, one year, 18 months, and two years (when patients were late in returning for visits their data were used up to three years).)
研究者
Michael Terrin
Professor
University of Maryland, Baltimore