Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial

NCT01756833 | Completed Phase 2 Results DMC

• 2 other identifiers: HP-00051170R01AG037120
• Study Type: interventional
• Target: 261
• Locations: 1 country
• Sites: 22

Brief Summary

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.

Conditions

Aneurysm

Keywords

abdominal; aortic; aneurysm

Outcome Measures

Primary Outcomes (1)

• Difference in Z-score for Rank of Maximum Transverse Diameter (MTD) Regressed on Z-score at Baseline to Assess Growth in Abdominal Aortic Aneurysm MTD Determined by CT Scans at Two-year Follow-up and Baseline (Pre-randomization).

  Diameters were ranked from smallest to largest. Worse ranks were assigned to surviving patients who underwent aneurysm repair (in order of longest to shortest time from randomization to repair), and worst ranks were assigned to patients who died (in order likewise). Each rank was converted to a z-score corresponding to the value on the standard normal curve of its percentile. The primary analysis was based on linear regression of the change in z-scores from baseline to 2 years. Independent variables were baseline z-score, sex, and a dichotomous variable for the randomly assigned treatment group (0 for placebo, 1 for doxycycline). Missing values were multiply imputed. Higher score corresponds to less favorable outcome. There is no scale associated with these z-scores; the absolute z-scores have no biological meaning or clinically relevant threshold. A z-score of 0 corresponds to the median rank. The maximum and minimum z-scores are +2.41 and -2.41. See References in Protocol Section.

  Baseline and two years from randomization (when patients were late in returning for visits, their data were used up to three years).

Secondary Outcomes (4)

• Maximum Transverse Diameter, cm

  Six months, one year, and two years (when patients were late in returning for visits their data were used up to three years).

• Volume, cm^3

  Six months, one year, and two years (when patients were late in returning for visits their data were used up to three years).

• MMP-9, ng/ml

  Six months, one year, 18 months, and two years (when patients were late in returning for visits their data were used up to three years).

• CRP, mg/l

  Six months, one year, 18 months, and two years (when patients were late in returning for visits their data were used up to three years).

Other Outcomes (3)

• Number of Participants With Aneurysm Rupture

  Two years

• Number of Participants With Surgical Intervention

  Two years

• Number of Participants Who Died

  Two years

Study Arms (2)

Doxycycline

ACTIVE COMPARATOR

100 mg capsules, twice a day, for a period of two years.

Drug: Doxycycline

Placebo

PLACEBO COMPARATOR

100 mg capsules, twice a day, for a period of two years.

Drug: Placebo

Interventions

Doxycycline DRUG

100 mg po bid

Also known as: doxycycline hyclate, Vibramycin, Oracea, Adoxa, Atridox and others

Doxycycline

Placebo DRUG

capsule identical to the doxycycline capsule

Also known as: capsule containing inert filler

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• National Institute on Aging (NIA): collaborator

Study Sites (22)

University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

Carondelet Heart & Vascular Institute

Tucson, Arizona, 85745, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Miami Cardiac and Vascular Institute

Miami, Florida, 33176, United States

Location

University of South Florida Health Center

Tampa, Florida, 33606, United States

Location

Northwestern University Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Beth Israel Deaconness Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

McLaren Northern Michigan

Petoskey, Michigan, 49770, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Omaha VAMC

Omaha, Nebraska, 68198, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97239, United States

Location

Portland VAMC

Portland, Oregon, 97239, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75216, United States

Location

University of Utah Health Sciences Center

Salt Lake City, Utah, 84132, United States

Location

Utah VAMC

Salt Lake City, Utah, 84132, United States

Location

Related Publications (7)

• Baxter BT, Matsumura J, Curci J, McBride R, Blackwelder WC, Liu X, Larson L, Terrin ML; N-TA(3)CT Investigators. Non-invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial (N-TA(3)CT): Design of a Phase IIb, placebo-controlled, double-blind, randomized clinical trial of doxycycline for the reduction of growth of small abdominal aortic aneurysm. Contemp Clin Trials. 2016 May;48:91-8. doi: 10.1016/j.cct.2016.03.008. Epub 2016 Mar 25.

  PMID: 27018941 BACKGROUND

• Lachin JM. Worst-Rank Score Methods-A Nonparametric Approach to Informatively Missing Data. JAMA. 2020 Oct 27;324(16):1670-1671. doi: 10.1001/jama.2020.7709. No abstract available.

  PMID: 32986071 BACKGROUND

• Lachin JM. Nonparametric Statistical Analysis. JAMA. 2020 May 26;323(20):2080-2081. doi: 10.1001/jama.2020.5874. No abstract available.

  PMID: 32453350 BACKGROUND

• Baxter BT, Matsumura J, Curci JA, McBride R, Larson L, Blackwelder W, Lam D, Wijesinha M, Terrin M; N-TA3CT Investigators. Effect of Doxycycline on Aneurysm Growth Among Patients With Small Infrarenal Abdominal Aortic Aneurysms: A Randomized Clinical Trial. JAMA. 2020 May 26;323(20):2029-2038. doi: 10.1001/jama.2020.5230.

  PMID: 32453369 RESULT

• Olson SL, Panthofer AM, Blackwelder W, Terrin ML, Curci JA, Baxter BT, Weaver FA, Matsumura JS; Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial Investigators. Role of volume in small abdominal aortic aneurysm surveillance. J Vasc Surg. 2022 Apr;75(4):1260-1267.e3. doi: 10.1016/j.jvs.2021.09.046. Epub 2021 Oct 14.

  PMID: 34655683 DERIVED

• Panthofer AM, Olson SL, Rademacher BL, Grudzinski JK, Chaikof EL, Matsumura JS; N-TA(3)CT Investigators. Anatomic eligibility for endovascular aneurysm repair preserved over 2 years of surveillance. J Vasc Surg. 2021 Nov;74(5):1527-1536.e1. doi: 10.1016/j.jvs.2021.04.044. Epub 2021 May 4.

  PMID: 33957227 DERIVED

• Olson SL, Wijesinha MA, Panthofer AM, Blackwelder WC, Upchurch GR Jr, Terrin ML, Curci JA, Baxter BT, Matsumura JS. Evaluating Growth Patterns of Abdominal Aortic Aneurysm Diameter With Serial Computed Tomography Surveillance. JAMA Surg. 2021 Apr 1;156(4):363-370. doi: 10.1001/jamasurg.2020.7190.

  PMID: 33595625 DERIVED

MeSH Terms

Conditions

Aneurysm

Interventions

Doxycycline

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Limitations and Caveats

Follow-up was limited to two years for most patients and results could differ with longer term follow-up.

Results Point of Contact

• Title: Michael L. Terrin, MDCM, MPH, Contact Principal Investigator
• Organization: University of Maryland School of Medicine

mterrin@som.umaryland.edu

410-706-6139

Study Officials

• Michael L Terrin, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

• Bernard T Baxter, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

• Jonathan Matsumura, MD

  University of Wisconsin Medical Center

  PRINCIPAL INVESTIGATOR

• John Curci, MD

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 20, 2012
• First Posted: December 28, 2012
• Study Start: May 1, 2013
• Primary Completion: July 23, 2019
• Study Completion: July 23, 2019
• Last Updated: November 26, 2021
• Results First Posted: November 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

US (22)