Adjunctive Treatment With Doxycycline to Enhance the Durability of Endovascular Aortic Aneurysm Repair

Sponsor

The Foundation for Barnes-Jewish Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT00126204

Collaborator

(none)

Enrollment

Location

Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Aneurysm	Drug: Doxycycline	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Adjunctive Treatment With Doxycycline in Endovascular Aneurysm Repair

Study Start Date :

Mar 1, 2004

Study Completion Date :

Jul 1, 2006

Outcome Measures

Primary Outcome Measures

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 []

Secondary Outcome Measures

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Presence of an abdominal aortic aneurysm (AAA) with a maximum diameter of > or = 4.5 cm
Planned aneurysm exclusion with endoluminal stent graft (any brand)

Exclusion Criteria:

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
Pregnancy
Ruptured AAA
Extension of covered portion of the graft above the renal arteries
Previous endoluminal aneurysm repair