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TuberculosisPhase 2NCT00144417

TBTC Study 28: Moxifloxacin Versus Isoniazid for TB Treatment

A Phase 2 study testing Moxifloxacin (with rifampin, pyrazinamide, and ethambutol) and isoniazid in people with Tuberculosis, run by Centers for Disease Control and Prevention at 26 sites in 6 countries.

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

This double-blind, randomized controlled trial evaluates moxifloxacin versus isoniazid in daily treatment during the first two months of treatment with rifampin, pyrazinamide and ethambutol for sputum smear-positive pulmonary tuberculosis. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tuberculosis
What is being tested?
Moxifloxacin (with rifampin, pyrazinamide, and ethambutol) and isoniazid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
433 participants
Where
26 sitesin 6 countries
Study dates
Feb 2006to Dec 2007
Phase
Phase 2
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Suspected pulmonary tuberculosis with acid-fast bacilli in a stained smear of expectorated or induced sputum. Patients whose sputum cultures do not grow M. tuberculosis and those having an M. tuberculosis isolate resistant to (one or more) isoniazid, rifampin, fluoroquinolones, will be discontinued from the study, but followed for 14 days to detect late toxicities from study therapy. Patients having extra-pulmonary manifestations of tuberculosis, in addition to smear-positive pulmonary disease, are eligible for enrollment. Sputum must be expectorated or induced; smear results from respiratory secretions obtained by bronchoalveolar lavage or bronchial wash may not be used for assessment of study eligibility.
  • Willingness to have HIV testing performed, if HIV serostatus is not known or if the last documented negative HIV test was more than 6 months prior to enrollment. HIV testing does not need to be repeated if there is written documentation of a positive test (positive ELISA and Western Blot or a plasma HIV-RNA level greater than 5000 copies/ml) at any time in the past.
  • 7 (seven) or fewer days of multidrug therapy for tuberculosis disease in the 6 months preceding enrollment.
  • 7 (seven) or fewer days of fluoroquinolone therapy in the 3 months preceding enrollment.
  • Age > 18 years
  • Karnofsky score of at least 60 (requires occasional assistance but is able to care for most of his/her needs; see Appendix B).
Show all 16Show fewer
  • Signed informed consent
  • Women with child-bearing potential must agree to practice an adequate (barrier) method of birth control or to abstain from heterosexual intercourse during study therapy.
  • Laboratory parameters done at, or <14 days prior to, screening:
  • Serum amino aspartate transferase (AST) activity ≤ 3 times the upper limit of normal
  • Serum total bilirubin level ≤ 2.5 times the upper limit of normal
  • Serum creatinine level ≤ 2 times the upper limit of normal
  • Complete blood count with hemoglobin level of at least 7.0 g/dL
  • Complete blood count with platelet count of at least 50,000/mm3
  • Serum potassium > 3.5 meq/L
  • Negative pregnancy test (women of childbearing potential)

Who cannot join

  • Breast-feeding
  • Known intolerance to any of the study drugs
  • Known allergy to any fluoroquinolone antibiotic
  • Concomitant disorders or conditions for which moxifloxacin (MXF), isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or ethambutol (EMB) are contraindicated. These include severe hepatic damage, acute liver disease of any cause, and acute uncontrolled gouty arthritis.
  • Current or planned therapy during the intensive phase of therapy using drugs having unacceptable interactions with rifampin (rifabutin can be substituted for rifampin during the continuation phase of therapy).
  • Current or planned antiretroviral therapy during the intensive phase of therapy.
Show all 9Show fewer
  • History of prolonged QT syndrome or current or planned therapy with quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine during the intensive phase of therapy.
  • Pulmonary silicosis
  • Central nervous system TB

Trial locations and contacts

26 sites in 6 countries.

26 sites in 6 countries

United States20 sites
  • Emory University School of Medicine

    Atlanta, Georgia, 30303

  • Johns Hopkins University School of Medicine

    Baltimore, Maryland, 21231

  • Boston University Medical Center

    Boston, Massachusetts, 02118

  • Northwestern University

    Chicago, Illinois, 60611

  • Denver Public Health Department

    Denver, Colorado, 80204

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of North Texas Health Science Center

    Fort Worth, Texas, 76104

  • Hines Veterans Administration Medical Center

    Hines, Illinois, 60141

  • Houston Veterans Administration Medical Center

    Houston, Texas, 77030

  • Veterans Administration Medical Center of Arkansas

    Little Rock, Arkansas, 72205

  • University of Southern California Medical Center

    Los Angeles, California, 90033

  • Veterans Administration Tennessee Valley Health Care System

    Nashville, Tennessee, 37232

  • Columbia University

    New York, New York, 10032

  • Harlem Hospital, Columbia University

    New York, New York, 10037

  • New Jersey School of Medicine

    Newark, New Jersey, 07103

  • Audie L Murphy Memorial Veterans Administration Medical Center

    San Antonio, Texas, 78284

  • University of California at San Diego

    San Diego, California, 92103

  • University of California, San Francincisco

    San Francisco, California, 94110

  • Seattle-King County Health Department

    Seattle, Washington, 98104

  • Washington DC Veterans Administration Medical Center

    Washington D.C., District of Columbia, 20422

Other trials in United States

Canada2 sites
  • Montreal Chest Institute

    Montreal, Quebec, H2X 2P4

  • University of Manitoba

    Winnepeg, Manitoba, R3A 1R8

Other trials in Canada

Brazil1 site
  • Hopital Universitario Clementino Fraga Filho

    Rio de Janeiro, Rio de Janeiro, 2194.590

Other trials in Brazil

South Africa1 site
  • Nelson R. Mandela School of Medicine

    Durban, KwaZulu-Natal

Other trials in South Africa

Spain1 site
  • Agencia de Salut Publica

    Barcelona, 08023

Other trials in Spain

Uganda1 site
  • Makerere University Medical School

    Kampala

Other trials in Uganda

About this study

Official title: TBTC Study 28: Evaluation of a Moxifloxacin-based, Isoniazid-sparing Regimen for Tuberculosis Treatment

This double-blind, randomized controlled trial evaluates moxifloxacin versus isoniazid in daily treatment during the first two months of treatment with rifampin, pyrazinamide and ethambutol for sputum smear-positive pulmonary tuberculosis.

Read the detailed description

The primary objective of this Phase 2 clinical trial is to compare the safety and antimicrobial activity of a moxifloxacin-containing regimen (moxifloxacin, rifampin, pyrazinamide, ethambutol [MRZE]) in which moxifloxacin has been substituted for isoniazid, to the standard control regimen (isoniazid, rifampin, pyrazinamide, ethambutol [HRZE]) in the first two months of treatment of sputum smear-positive pulmonary tuberculosis. The assessment of antimicrobial activity will be sputum culture-conversion. Higher rates of sputum culture conversion after 2 months of treatment with a moxifloxacin-containing regimen would support Phase 3 clinical trials of moxifloxacin in treatment regimens of less than the current 6 month standard regimens.

Rationale - Current treatment of smear positive pulmonary tuberculosis requires a minimum of 6 months, a treatment duration that is challenging for patients and tuberculosis control programs. Therefore, a high priority in tuberculosis research is the identification of agents that can shorten treatment. Several fluoroquinolone antibiotics have potent activity against Mycobacterium tuberculosis (M. tuberculosis) in preclinical testing. Of the currently available fluoroquinolones, moxifloxacin has excellent activity in vitro and in animal models of tuberculosis, a favorable pharmacokinetic profile (serum half-life of 10-12 hours), lack of problematic drug-drug interactions, no need for dosage adjustment for renal and hepatic insufficiency, and an excellent safety profile. In addition, in the murine model of tuberculosis, the substitution of moxifloxacin for isoniazid resulted in significant reductions in the time to culture conversion and the time to sterilization when compared to the standard combination rifampin, isoniazid and pyrazinamide. However, moxifloxacin has not been fully evaluated in humans for tuberculosis treatment. There is a need to assess not only the anti-tuberculosis activity of moxifloxacin-containing regimens, but also the safety of more prolonged therapy with moxifloxacin.

Two-month culture conversion rates are a well-accepted surrogate marker for the sterilizing activity of anti-tuberculosis drugs. Rifampin and pyrazinamide, the key drugs in current 6-month regimens, markedly increase 2-month culture-conversion rates. Therefore, this study will use 2-month culture conversion rate as the measure of antimicrobial activity of moxifloxacin.

Conditions
Tuberculosis
Being tested
Moxifloxacin (with rifampin, pyrazinamide, and ethambutol), isoniazid
Keywords
tuberculosis, TB, treatment, efficacy, safety
Medical subject headings
Tuberculosis

What participants receive

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

  • Moxifloxacin (with rifampin, pyrazinamide, and ethambutol)Drug

    Moxifloxacin 400mg daily, 8 weeks

  • isoniazidDrug

    isoniazid, oral, 300 mg, daily, 8 weeks

Study groups in NCT00144417
Study groupRoleWhat they receive
HRZEActive comparatorisoniazid, rifampin, pyrazinamide, ethambutol, moxifloxacin-placebo
Receives: Drug: isoniazid
MRZEExperimentalmoxifloxacin, rifampin, pyrazinamide, ethambutol, isoniazid-placebo
Receives: Drug: Moxifloxacin (with rifampin, pyrazinamide, and ethambutol)

What is being measured

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

  1. • To compare the culture-conversion rate at the end of the intensive phase of therapy of the moxifloxacin regimen vs. that of the isoniazid regimen

    Measured: 8 weeks

Secondary outcomes (6)
  1. To compare the safety and tolerability of the moxifloxacin regimen to that of the isoniazid regimen

    Measured: 8 weeks

  2. To determine the time to culture-conversion of the moxifloxacin regimen and the isoniazid regimen using data from 2-, 4-, 6-, and 8-week cultures

    Measured: 8 weeks

  3. To compare the proportion of patients with any Grade 3 or 4 adverse reactions

    Measured: 8 weeks

  4. To compare adverse events and 2-month culture conversion rates among HIV-infected patients vs. HIV-uninfected patients

    Measured: 8 weeks

  5. To compare the rates of treatment failure of the moxifloxacin regimen and the isoniazid regimen

    Measured: 6 months

  6. To determine whether there is delayed toxicity attributable to moxifloxacin (toxicity that becomes evident after the 8 weeks of moxifloxacin therapy)

    Measured: 6 months

Timeline

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

  1. First posted5 Sep 2005 (estimated)
  2. Study startFeb 2006
  3. Primary completionJun 2007
  4. Study completionDec 2007

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
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
433 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00144417
Sponsor's protocol ID
CDC-NCHSTP-4448
Status last verified
Jun 2011
First submitted
1 Sep 2005
Last updated
3 Aug 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • Dorman SE, Johnson JL, Goldberg S, Muzanye G, Padayatchi N, Bozeman L, Heilig CM, Bernardo J, Choudhri S, Grosset JH, Guy E, Guyadeen P, Leus MC, Maltas G, Menzies D, Nuermberger EL, Villarino M, Vernon A, Chaisson RE; Tuberculosis Trials Consortium. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. Am J Respir Crit Care Med. 2009 Aug 1;180(3):273-80. doi: 10.1164/rccm.200901-0078OC. Epub 2009 Apr 30.

    PubMed 19406981
  • Zhang N, Savic RM, Boeree MJ, Peloquin CA, Weiner M, Heinrich N, Bliven-Sizemore E, Phillips PPJ, Hoelscher M, Whitworth W, Morlock G, Posey J, Stout JE, Mac Kenzie W, Aarnoutse R, Dooley KE; Tuberculosis Trials Consortium (TBTC) and Pan African Consortium for the Evaluation of Antituberculosis Antibiotics (PanACEA) Networks. Optimising pyrazinamide for the treatment of tuberculosis. Eur Respir J. 2021 Jul 20;58(1):2002013. doi: 10.1183/13993003.02013-2020. Print 2021 Jul.

    PubMed 33542052
  • Mac Kenzie WR, Heilig CM, Bozeman L, Johnson JL, Muzanye G, Dunbar D, Jost KC Jr, Diem L, Metchock B, Eisenach K, Dorman S, Goldberg S. Geographic differences in time to culture conversion in liquid media: Tuberculosis Trials Consortium study 28. Culture conversion is delayed in Africa. PLoS One. 2011 Apr 11;6(4):e18358. doi: 10.1371/journal.pone.0018358.

    PubMed 21494548

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Moxifloxacin (with rifampin, pyrazinamide, and ethambutol) and isoniazid in people with Tuberculosis, run by Centers for Disease Control and Prevention at 26 sites in 6 countries.

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 16 inclusion and 9 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 3 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States, Canada, Brazil, South Africa, Spain and 1 more country. 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. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

• To compare the culture-conversion rate at the end of the intensive phase of therapy of the moxifloxacin regimen vs. that of the isoniazid regimen (time frame: 8 weeks). 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 NCT00144417, which also lists 3 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 3 Aug 2011.

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