Department of Surgery, University of Nebraska School of Medicine, Omaha.
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison.
JAMA. 2020 May 26;323(20):2029-2038. doi: 10.1001/jama.2020.5230.
Abdominal aortic aneurysms affect more than 3% of US older adults.
To test whether doxycycline reduces the growth of abdominal aortic aneurysm over 2 years as measured by maximum transverse diameter.
DESIGN, SETTING, AND PARTICIPANTS: Parallel, 2-group, randomized clinical trial that was conducted at 22 US clinical centers between May 2013 and January 2017, and enrolled patients 50 years or older with small (3.5-5.0 cm for men, 3.5-4.5 cm for women) infrarenal aneurysms. The final date of follow-up was July 31, 2018.
Patients were randomized to receive twice daily for 2 years doxycycline 100 mg orally (as capsules) (n = 133) or placebo (n = 128).
The primary outcome was change in abdominal aortic aneurysm maximum transverse diameter measured from CT images at baseline and follow-up at 2 years. Patients were assigned ranks based on the maximum transverse diameter (measured or imputed) of the aorta and also if they underwent aneurysm repair or died. The ranks were converted to scores having a normal distribution to facilitate the primary analysis ("normal scores").
Of 261 patients randomized, no follow-up CT scans were obtained on 7 (3%), leaving a final analysis set of 129 patients assigned to doxycycline and 125 to placebo (mean [SD] age, 71.0 years [7.4 years], 35 women [14%]). The outcome normal scores used in the primary analysis were based on maximum transverse diameter (measured or imputed) in 113 patients (88%) in the doxycycline group and 112 patients (90%) in the placebo group; aneurysm repair in 13 (10%) and 9 (7%), and death in 3 (2%) and 4 (3%), respectively. The primary outcome, normal scores reflecting change in aortic diameter, did not differ significantly between the 2 groups, mean change in normal scores, 0.0262 vs -0.0258 (1-sided P = .71). Mean (SD) baseline maximum transverse diameter was 4.3 cm (0.4 cm) for doxycycline and 4.3 cm (0.4 cm) for placebo. At the 2-year follow-up, the change in measured maximum transverse diameter was 0.36 cm (95% CI, 0.31 to 0.40 cm) for 96 patients in the doxycycline group vs 0.36 cm (95% CI, 0.30 to 0.41 cm) for 101 patients in the placebo group (difference, 0.0; 95% CI, -0.07 to 0.07 cm; 2-sided P = .93). No patients were withdrawn from the study because of adverse effects. Joint pain occurred in 84 of 129 patients (65%) with doxycycline and 79 of 125 (63%) with placebo.
Among patients with small infrarenal abdominal aortic aneurysms, doxycycline compared with placebo did not significantly reduce aneurysm growth at 2 years. These findings do not support the use of doxycycline for reducing the growth of small abdominal aortic aneurysms.
ClinicalTrials.gov Identifier: NCT01756833.
腹主动脉瘤影响超过 3%的美国老年患者。
测试多西环素是否能在 2 年内通过最大横径测量来减少腹主动脉瘤的生长。
设计、设置和参与者：这是一项在美国 22 个临床中心进行的 2 组平行随机临床试验，于 2013 年 5 月至 2017 年 1 月期间招募了 50 岁及以上、瘤径较小（男性为 3.5-5.0cm，女性为 3.5-4.5cm）的肾下型腹主动脉瘤患者。最后随访日期为 2018 年 7 月 31 日。
患者随机分为每日两次、连续 2 年口服多西环素 100mg（胶囊）（n=133）或安慰剂（n=128）组。
主要结果是从 CT 图像基线和 2 年随访时测量的腹主动脉瘤最大横径的变化。根据主动脉最大横径（测量或推断）和是否接受动脉瘤修复或死亡，对患者进行排名。这些排名被转换为具有正态分布的分数，以便于主要分析（“正常分数”）。
在 261 名随机患者中，有 7 名（3%）未进行随访 CT 扫描，最终分析集为 129 名接受多西环素治疗和 125 名接受安慰剂治疗的患者（平均年龄 71.0 岁[7.4 岁]，女性 35 名[14%]）。主要分析中使用的结果正常分数基于 113 名（88%）多西环素组和 112 名（90%）安慰剂组患者的最大横径（测量或推断）；动脉瘤修复分别为 13 名（10%）和 9 名（7%），死亡分别为 3 名（2%）和 4 名（3%）。主要结局，反映主动脉直径变化的正常分数在两组之间没有显著差异，正常分数的平均变化为 0.0262 与-0.0258（单侧 P=0.71）。多西环素组和安慰剂组的基线最大横径分别为 4.3cm（0.4cm）和 4.3cm（0.4cm）。在 2 年随访时，多西环素组 96 名患者的最大横径测量值变化为 0.36cm（95%CI，0.31-0.40cm），安慰剂组 101 名患者的变化为 0.36cm（95%CI，0.30-0.41cm）（差值为 0.0；95%CI，-0.07 至 0.07cm；双侧 P=0.93）。没有患者因不良反应而退出研究。多西环素组 129 名患者中有 84 名（65%）和安慰剂组 125 名患者中有 79 名（63%）出现关节疼痛。
在患有小肾下型腹主动脉瘤的患者中，与安慰剂相比，多西环素在 2 年内并未显著减少动脉瘤生长。这些发现不支持使用多西环素来减少小的腹主动脉瘤的生长。
ClinicalTrials.gov 标识符：NCT01756833。
