The durability of endovascular aneurysm repair (EVAR) has been limited by development of
endoleaks which may be secondary to progressive aortic degeneration by matrix
metalloproteases (MMP). Doxycycline is a known inhibitor of the MMP family of enzymes in
aneurysms. The investigators propose a randomized, controlled trial of adjuvant doxycycline
therapy with EVAR to determine its effects on re-intervention, aneurysm shrinkage and serum
markers of aneurysmal degeneration.
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.
- Presence of an abdominal aortic aneurysm (AAA) with a maximum diameter of > or = 4.5
- Planned aneurysm exclusion with endoluminal stent graft (any brand)
- Known malignancy not to include prostate cancer or any history of cancer that has not
had a recurrence in the last 5 years.
- Hypersensitivity to doxycycline or any of its components
- Ruptured AAA
- Extension of covered portion of the graft above the renal arteries
- Previous endoluminal aneurysm repair