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AneurysmPhase 2N-TA^3CTNCT01756833

Non-Invasive Treatment of Abdominal Aortic Aneurysm Clinical Trial

A Phase 2 study testing Doxycycline in people with Aneurysm, run by University of Maryland, Baltimore at 22 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 years and olderHealthy volunteers can take part
Conditions the study is for
Aneurysm
What is being tested?
Doxycycline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
261 participants
Where
22 sitesUnited States
Study dates
May 2013to 23 Jul 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 years and older
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.

Trial locations and contacts

22 sites in 1 country.

22 sites in 1 country

United States22 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • University of Maryland Medical Center

    Baltimore, Maryland, 21201

  • Beth Israel Deaconness Medical Center

    Boston, Massachusetts, 02215

  • Northwestern University Memorial Hospital

    Chicago, Illinois, 60611

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75216

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • University of Southern California

    Los Angeles, California, 90033

  • Miami Cardiac and Vascular Institute

    Miami, Florida, 33176

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

  • Columbia University Medical Center

    New York, New York, 10032

  • Omaha VAMC

    Omaha, Nebraska, 68198

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • McLaren Northern Michigan

    Petoskey, Michigan, 49770

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • Portland VAMC

    Portland, Oregon, 97239

  • University of Utah Health Sciences Center

    Salt Lake City, Utah, 84132

  • Utah VAMC

    Salt Lake City, Utah, 84132

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University

    Stanford, California, 94305

  • University of South Florida Health Center

    Tampa, Florida, 33606

  • University of Arizona Medical Center

    Tucson, Arizona, 85724

  • Carondelet Heart & Vascular Institute

    Tucson, Arizona, 85745

Other trials in United States

About this study

Official title: 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.

Read the detailed description

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. Nineteen clinical sites have identified pools of over 1600 patients with small aneurysm who meet the proposed inclusion/exclusion criteria. Two hundred fifty-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.

Conditions
Aneurysm
Being tested
Doxycycline, Placebo
Keywords
abdominal, aortic, aneurysm
Medical subject headings
Aneurysm

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxycyclineDrug

    Also called doxycycline hyclate, Vibramycin, Oracea, Adoxa

    100 mg po bid

  • PlaceboDrug

    Also called capsule containing inert filler

    capsule identical to the doxycycline capsule

Study groups in NCT01756833
Study groupRoleWhat they receive
DoxycyclineActive comparator100 mg capsules, twice a day, for a period of two years.
Receives: Drug: Doxycycline
PlaceboPlacebo comparator100 mg capsules, twice a day, for a period of two years.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Maximum Transverse Diameter, cm

    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). When patients were late in returning for visits their data were used up to three years.

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

  2. Volume, cm^3

    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). When patients were late in returning for visits their data were used up to three years.

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

  3. MMP-9, ng/ml

    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). When patients were late in returning for visits their data were used up to three years.

    Analysis of hs-CRP will be performed using an immunoturbidimetric latex agglutination method (K-assay [KAI-60], Kamiya Biomedical Co., Seattle, WA).

    Measured: 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).

  4. CRP, mg/l

    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). When patients were late in returning for visits their data were used up to three years.

    Plasma MMP-9 concentrations will be measured by an ELISA, two-site sandwich method that is commercially available (R \& D Systems, Quantikine, DMP900).

    Measured: 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).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Dec 2012 (estimated)
  2. Study startMay 2013
  3. Primary completion23 Jul 2019
  4. Study completion23 Jul 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
261 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01756833
Sponsor's protocol ID
HP-00051170
Other IDs
R01AG037120
Acronym
N-TA^3CT
Status last verified
Oct 2021
First submitted
20 Dec 2012
Last updated
26 Nov 2021
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • 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.

    PubMed 27018941

  • 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.

    PubMed 32986071

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

    PubMed 32453350

  • 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.

    PubMed 32453369

  • 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.

    PubMed 34655683

  • 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.

    PubMed 33957227

  • 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.

    PubMed 33595625

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxycycline in people with Aneurysm, run by University of Maryland, Baltimore at 22 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). (time frame: Baseline and two years from randomization (when patients were late in returning for visits, their data were used up to three years).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01756833, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2021.

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