Adjunctive Treatment With Doxycycline to Enhance the Durability of Endovascular Aortic Aneurysm Repair
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Adjunctive Treatment With Doxycycline in Endovascular Aneurysm Repair|
- Change in aortic measurements by > 2 mm on 2 consecutive scans
- Change in aortic measurement by > 5 mm on a single scan
- 50% reduction in baseline plasma MMP-9 at 6 months
- Significant reductions at 6 months in serum interleukin-6 (IL-6)
- Significant reductions at 6 months in serum IL-8
- Significant reductions at 6 months in serum interferon-gamma
- Significant reductions at 6 months in serum C-reactive protein
|Study Start Date:||March 2004|
|Estimated Study Completion Date:||July 2006|
Patients will be consented and enrolled at the time of their clinic visit or admission to the hospital for a planned EVAR, in accordance with institutional review board guidelines. Demographic, risk factor and medication regimen data will be obtained from the patient's clinical chart. Patients will be randomized to doxycycline therapy (100 mg taken twice daily) or a placebo. The patients will receive their first dose of study medication on the day following surgery, and continue the study therapy for 6 months.
Plasma and serum will be obtained at the time of enrollment (baseline), and at each post-operative follow-up visit during the study as outlined above. Aliquots will be stored at -80ºC until assayed. Measurements of the circulating markers will be performed by commercially available assays for plasma MMP-9 (R&D Systems, Minneapolis, MN), serum IL-6 (R&D Systems) , IL-8 (R&D Systems), IFN-gamma (R&D Systems), and CRP (Bio-Check, Burlingame, CA) Data will be collected from the pre-operative and all post-operative CT scans regarding maximal aneurysm diameter and transverse neck diameter at 5 mm, 10 mm and 15 mm below the takeoff of the lowest renal artery. All documented endoleaks and their clinical type will be recorded, as will any re-intervention related to the graft or aneurysm.
The primary end-points of the study related to aneurysm measurements will be an increase or decrease in any of the diameter measurements of the aorta by 2 mm or more on 2 consecutive CT scans or a change of 5 mm or more on any single scan. Of the circulating markers, an additional primary endpoint will be a 50% reduction in baseline MMP-9 after endografting. Secondary endpoints will be significant reductions over baseline in circulating IL-6, IL-8, IFN-γ, and CRP. An a priori power analysis indicates that at 6 months, reductions in circulating levels of these markers by 50% can be detected with a β-error of less than 0.1 and α-error of less than 0.05.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00126204
|United States, Missouri|
|Washington University School of Medicine / Barnes-Jewish Hospital|
|St. Louis, Missouri, United States, 63110|
|Principal Investigator:||John A Curci, MD||Washington University School of Medicine|