Oral doxycycline did not slow growth of small infrarenal abdominal aortic aneurysms in the randomized N-TA3 CT trial, researchers reported.
Changes in aortic diameter with the antibiotic to reduce inflammation were no different than with placebo at 2 years (one-sided P=0.71), using a nonparametric analysis to simultaneously account for the ranked outcomes of maximum transverse diameter of the aorta (measured or imputed), aneurysm repair, and death.
From measurements on CT, aortic diameters grew by the same +0.36 cm over that period in both doxycycline recipients and controls, found Michael Terrin, MDCM, MPH, of the University of Maryland School of Medicine in Baltimore, and colleagues.
“This study found doxycycline treatment and CT scan follow-up to be feasible, but doxycycline in the dose tested in this study did not reduce the growth of small abdominal aortic aneurysms or reduce the circulating level of MMP-9, the enzyme most strongly implicated in tissue disruption in animal models,” they wrote in a paper published online in JAMA.
Even though N-TA3 CT did not produce positive results for the tetracycline antibiotic tested, the trial did show that maximum transverse diameters on small abdominal aortic aneurysms did not quickly become larger or smaller over 2 years.
“The annual rate of growth observed is smaller than previously reported, suggesting that intervals between CT scan imaging may be lengthened,” according to Terrin’s team.
No pharmaceutical agent has been proven to reduce the rate of growth or prevent rupture of abdominal aortic aneurysms, they said. For bigger aneurysms (>5.5 cm in men or 5.0 cm in women), the sole treatment is open or endovascular repair, they noted.
N-TA3 CT enrolled people with abdominal aortic aneurysms in the size range of 3.5-5.0 cm for men and 3.5-4.5 cm for women.
The phase IIb trial, conducted at 22 U.S. centers, screened 1,420 individuals to get 261 randomized to doxycycline (100 mg twice daily) or placebo. Final analysis was performed on the 254 who had follow-up CTs (mean age 71.0 years, 14% women, 76% white).
Doxycycline and placebo groups shared similar baseline characteristics. Maximum transverse diameter of the aorta was 4.3 cm in both arms.
No patient withdrew from the study because of adverse effects, the most common of which was frequent joint pain (65% of doxycycline and 63% of placebo users).
The two groups shared similar rates of death (2.3% vs 3.2%, P=0.67) and aneurysm repair (10.1% vs 7.2%, P=0.41). No ruptures were observed over the course of the study.
Adherence to assigned treatment was 80% or better in 60% of the doxycycline arm and 69% of the placebo arm. Less than 50% adherence was observed in 18% and 14% of the groups, respectively.
Doxycycline remained no better than placebo on per-protocol analysis, according to Terrin and colleagues.
They acknowledged that their study was limited by the 2-year follow-up. In addition, the fact that the study population represented only 18% of those screened may reflect some biases.
“However, the reasons patients did not agree to participate or were ineligible (other serious comorbid states, inconvenience of follow-up procedures) are not likely to be associated with aneurysm growth,” the investigators maintained.
Last Updated May 27, 2020
Disclosures
The trial was funded by an NIH grant.
Terrin reported receiving grants from the NIH.
Source: MedicalNewsToday.com
