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

Aortic Aneurysm Clinical Trial

Official title:

Adjunctive Treatment With Doxycycline in Endovascular Aneurysm Repair

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00126204
• Other study ID #: 00012-0904-02
• Status: Completed
• Phase: N/A
• First received: August 2, 2005
• Last updated: March 3, 2010
• Start date: March 2004
• Est. completion date: July 2006

Study information

• Verified date: September 2006
• Source: Barnes-Jewish Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aneurysm
• Aortic Aneurysm

Intervention

Drug:
• Doxycycline

Locations

Country	Name	City	State
United States	Washington University School of Medicine / Barnes-Jewish Hospital	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Barnes-Jewish Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

Hackmann AE, Rubin BG, Sanchez LA, Geraghty PA, Thompson RW, Curci JA. A randomized, placebo-controlled trial of doxycycline after endoluminal aneurysm repair. J Vasc Surg. 2008 Sep;48(3):519-26; discussion 526. doi: 10.1016/j.jvs.2008.03.064. Epub 2008 J — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in aortic measurements by > 2 mm on 2 consecutive scans
Primary	Change in aortic measurement by > 5 mm on a single scan
Primary	50% reduction in baseline plasma MMP-9 at 6 months
Secondary	Significant reductions at 6 months in serum interleukin-6 (IL-6)
Secondary	Significant reductions at 6 months in serum IL-8
Secondary	Significant reductions at 6 months in serum interferon-gamma
Secondary	Significant reductions at 6 months in serum C-reactive protein