Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study.

Abstract

BACKGROUND:

The primary purpose of this study was to evaluate compliance, side effects, and safety associated with prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms (AAAs). A secondary goal was to determine how treatment with doxycycline influences circulating levels of matrix metalloproteinase-9 (MMP-9) in this patient population.

METHODS:

Thirty-six patients with AAAs (30 men and 6 women; mean age, 69 +/- 1 years) were enrolled into a 6-month phase II study to evaluate treatment with doxycycline (100 mg orally twice a day). Aneurysm size was measured before and after treatment, and compliance and side effects were monitored. Plasma levels of doxycycline were measured midway through the study, and plasma MMP-9 concentrations were measured at baseline, 3 months, and 6 months.

RESULTS:

Thirty-three of the 36 patients (92%) completed 6 months of doxycycline treatment. Significant treatment-related side effects occurred in five patients (13.9%), including three with cutaneous photosensitivity reactions (8.3%), one with tooth discoloration (2.8%), and one with yeast infection (2.8%). A high rate of compliance with treatment was seen, despite minor but frequent side effects, including nonspecific gastrointestinal symptoms (25%), easily managed episodes of photosensitivity (22.2%), and reversible tooth discoloration (5.5%). The mean plasma doxycycline level after 3 months was 4.62 +/- 0.68 ug/mL (median, 3.64 microg/mL; range, 1.31 to 14.39 microg/mL; n = 23 patients). No significant change was seen in AAA diameter (42.7 +/- 1.3 mm at 6 months versus 41.0 +/- 0.9 mm at baseline), and the overall rate of AAA expansion was 0.63% +/- 0.25% per month. The mean plasma MMP-9 level (n = 19 patients) was elevated at baseline (118.9 +/- 37.9 ng/mL; upper limit of normal, 85 ng/mL) but subsequently decreased to 83.8 +/- 32.9 ng/mL at 3 months (not significant versus baseline) and to 66.4 +/- 24.2 ng/mL at 6 months (P =.022 versus baseline). Only 21% of patients had an elevated level of plasma MMP-9 after 6 months of treatment compared with 47% at baseline (P <.05).

CONCLUSION:

Prolonged administration of doxycycline is safe and well tolerated by patients with small asymptomatic AAAs and is associated with a gradual reduction in plasma MMP-9 levels. Further studies are needed to evaluate the long-term effects of doxycycline on the rate and extent of aneurysm growth and the potential use of plasma MMP-9 levels as a biomarker of aneurysm disease progression.

• Authors: B Timothy Baxter, William H Pearce, Eugene A Waltke, Fred N Littooy, John W Hallett Jr, K Craig Kent, Gilbert R Upchurch Jr, Elliot L Chaikof, Joseph L Mills, Beverly Fleckten, G Matt Longo, Jason K Lee, Robert W Thompson
• Journal: Journal of vascular surgery (J Vasc Surg) Vol. 36 Issue 1 Pg. 1-12 (Jul 2002) ISSN: 0741-5214 [Print] United States
• PMID: 12096249 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Biomarkers
• Matrix Metalloproteinase 9
• Doxycycline

Topics

• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (administration & dosage, adverse effects, blood)
• Aortic Aneurysm, Abdominal (drug therapy)
• Biomarkers (blood)
• Disease Progression
• Doxycycline (administration & dosage, adverse effects, blood)
• Female
• Follow-Up Studies
• Humans
• Male
• Matrix Metalloproteinase 9 (blood, drug effects)
• Middle Aged
• Patient Compliance
• Prospective Studies
• Statistics as Topic
• Time Factors
• Tomography, X-Ray Computed
• Treatment Outcome