Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Maryland
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michael Terrin, MD, University of Maryland
ClinicalTrials.gov Identifier:
NCT01756833
First received: December 20, 2012
Last updated: November 20, 2013
Last verified: November 2013

December 20, 2012
November 20, 2013
May 2013
June 2016   (final data collection date for primary outcome measure)
The primary outcome is growth in abdominal aortic aneurysm (AAA) maximum transverse diameter determined by CT scans at two-year follow-up with allowance for baseline (pre-randomization) diameter. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
Based on an anticipated growth rate of 2.5 mm per year in the placebo group and the current threshold at which surgical intervention will be offered to trial participants, (5.5 cm in men, 5.0 cm in women), the upper limit of AAA size for inclusion has been set at 5.0 cm for men and 4.5 cm for women. Among these subjects, the threshold for surgical repair would be exceeded only by those exhibiting persistent growth.
Same as current
Complete list of historical versions of study NCT01756833 on ClinicalTrials.gov Archive Site
  • Secondary outcomes will determine if doxycycline affects other measures, e.g., MMP-9 levels in plasma, and whether these effects are related to aneurysm growth. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
    Secondary outcomes will derive from central, Imaging Core Laboratory analyses of the CT scans performed every six months on patients and from the clinical follow-up of randomized patients, from clinical observation, local laboratory findings, study visit quality of life assessments, and from biomarker analyses to be performed in the Biomarkers Core Laboratory (e.g., changes from initial matrix metalloproteinase (MMP-9) levels, and matrix metalloproteinase (MMP-9) levels at 24 months of follow-up).
  • Secondary outcomes will determine if doxycycline affects other measures, e.g., Interferon-gamma levels, and whether these effects are related to aneurysm growth. [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
    Secondary outcomes will derive from central, Imaging Core Laboratory analyses of the CT scans performed every six months on patients and from the clinical follow-up of randomized patients, from clinical observation, local laboratory findings, study visit quality of life assessments, and from biomarker analyses to be performed in the Biomarkers Core Laboratory (e.g., changes from initial Interferon-gamma levels, and Interferon-gamma levels at 24 months of follow-up).
Same as current
  • Aneurysm volume and other characteristics [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Aneurysm rupture [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Surgical intervention [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Aneurysm volume and other characteristics [ Time Frame: Three and one-half years. ] [ Designated as safety issue: No ]
  • Aneurysm rupture [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Surgical intervention [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
  • Death [ Time Frame: Three and one-half years ] [ Designated as safety issue: No ]
 
Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial
Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA^3CT)

The primary aim of this study is to determine if doxycycline (100 mg bid) will inhibit (by at least 40%) the increase in greatest transverse diameter of small abdominal aortic aneurysms (3.5-5.0 cm in men, 3.5-4.5 cm in women) over a 24-month period of observation in comparison to a placebo-treated control group.

N-TA^3CT is a randomized, double-blind, placebo-controlled test of the hypothesis that doxycycline 100 mg bid, will reduce the rate of increase of maximum transverse diameter of small (3.5-5.0 cm among men and 3.5 to 4.5 cm among women) abdominal aortic aneurysms. The primary outcome is abdominal aortic aneurysm (AAA) maximum transverse diameter determined by CT scans at two-year follow-up with allowance for baseline (pre-randomization) diameter. Based on an anticipated growth rate of 2.5 mm per year in the placebo group and the current threshold at which surgical intervention will be offered to trial participants, (5.5 cm in men, 5.0 cm in women), the upper limit of AAA size for inclusion has been set at 5.0 cm for men and 4.5 cm for women. Among these subjects, the threshold for repair would be exceeded only by those exhibiting persistent growth. Secondary outcomes will determine if doxycycline affects other measures, e.g., MMP-9 levels in plasma and whether these effects are related to aneurysm growth. Fifteen clinical sites have identified pools of over 900 patients with small aneurysm who meet the proposed inclusion/exclusion criteria. Two hundred forty-eight patients will be randomized to placebo or doxycycline and their aneurysms followed for change in diameter at six-month intervals using CT imaging. The alternative hypothesis is that doxycycline will inhibit the expansion rate by 40% during the two years of observation. Patients enrolling in N-TA^3CT must be able to give consent for their participation themselves and meet study eligibility criteria.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Aneurysm
  • Drug: Doxycycline
    Other Names:
    • doxycycline hyclate
    • Vibramycin
    • Oracea
    • Adoxa
    • Atridox and others
  • Drug: Placebo
  • Active Comparator: Doxycycline
    100 mg capsules, twice a day, for a period of two years.
    Intervention: Drug: Doxycycline
  • Placebo Comparator: Placebo
    100 mg capsules, twice a day, for a period of two years.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
248
June 2017
June 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients 55 years of age or older, women post-surgical menopause or at least two years since last menses if natural menopause.
  • CT scan documented infrarenal abdominal aortic aneurysm with maximum transverse diameter larger than 35 mm and no greater than 50 mm, in men, and larger than 35 mm and no greater than 45 mm in women.

Exclusion Criteria:

  • Patients will be excluded from the study if they are unable to give their own informed consent to participate.
  • have symptoms related to abdominal aortic aneurysm.
  • have other intra-abdominal vascular pathology that may require repair within 24 months (e.g., renal artery stenosis, large iliac artery aneurysms, iliac occlusive disease, aneurysmal involvement of the renal artery).
  • have had previous abdominal aortic aneurysm repair by open surgical or endovascular technique.
  • have an active malignancy with life expectancy less than two years.
  • have an allergy to tetracycline.
  • are currently or have been recently treated (previous six months) with tetracycline derivatives.
  • they are currently taking anti-seizure medicines metabolized by pathways influenced by doxycycline (e.g., carbamazepine, phenytoin, and barbiturates).
  • stage II hypertension (patients whose blood pressure is persistently in the range of systolic > 160 mm Hg or diastolic > 100 mm Hg despite primary physician's best effort to achieve adequate therapy.
  • have dialysis dependent renal failure or impending dialysis treatment for renal insufficiency.
  • have a chronic infection requiring long-term (> 2 weeks) antibiotics.
  • have known genetic syndromes responsible for the abdominal aortic aneurysm (e.g., Marfan's Syndrome).
  • are under treatment with systemic immunosuppressive agents.
  • could become pregnant.
  • are not good candidates for clinical trial participation.
  • are enrolled in another clinical trial.
Both
55 Years and older
Yes
Contact: Michael L Terrin, MD 410-706-6139 mterrin@epi.umaryland.edu
Contact: Andrea Lefever 410-706-4411 alefever@epi.umaryland.edu
United States
 
NCT01756833
HP-00051170, R01AG037120
Yes
Michael Terrin, MD, University of Maryland
University of Maryland
National Institute on Aging (NIA)
Principal Investigator: Michael L Terrin, MD University of Maryland, Baltimore County
Principal Investigator: Bernard T Baxter, MD University of Nebraska
Principal Investigator: Jonathan Matsumura, MD University of Wisconsin Medical Center
Principal Investigator: John Curci, MD Washington University School of Medicine
University of Maryland
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP