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

This study has been completed.
Sponsor:
Information provided by:
Barnes-Jewish Hospital
ClinicalTrials.gov Identifier:
NCT00126204
First received: August 2, 2005
Last updated: March 3, 2010
Last verified: September 2006
  Purpose

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 Intervention
Aortic Aneurysm
Drug: Doxycycline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Adjunctive Treatment With Doxycycline in Endovascular Aneurysm Repair

Resource links provided by NLM:


Further study details as provided by Barnes-Jewish Hospital:

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

Estimated Enrollment: 75
Study Start Date: March 2004
Estimated Study Completion Date: July 2006
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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00126204

Locations
United States, Missouri
Washington University School of Medicine / Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Barnes-Jewish Hospital
Investigators
Principal Investigator: John A Curci, MD Washington University School of Medicine
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00126204     History of Changes
Other Study ID Numbers: 00012-0904-02
Study First Received: August 2, 2005
Last Updated: March 3, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Barnes-Jewish Hospital:
endoleak
doxycycline
matrix metalloproteinase
inflammation
endograft
circulating markers

Additional relevant MeSH terms:
Aneurysm
Aortic Aneurysm
Aortic Diseases
Cardiovascular Diseases
Vascular Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014