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TBTC Study 30: Safety and Tolerability of Low Dose Linezolid in MDR TB (LiMiT)

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ClinicalTrials.gov Identifier: NCT00664313
Recruitment Status : Completed
First Posted : April 22, 2008
Last Update Posted : October 2, 2012
University of KwaZulu
Columbia University
Yale University
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Brief Summary:
The antibiotic linezolid when given for the treatment of multi-drug resistant tuberculosis is safe and tolerated at a low dose (600 mg daily) for a limited duration (16 weeks)

Condition or disease Intervention/treatment Phase
Multi-drug Resistant Tuberculosis Extensively Drug Resistant Tuberculosis Drug: Linezolid Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: TBTC Study 30: A Phase I/II Pilot Study for Evaluation of Low Dose, Once Daily, Linezolid Plus Optimized Background Therapy (OBT) Versus Placebo Plus OBT for the Treatment of Multi-drug Resistant Tuberculosis
Study Start Date : April 2009
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Linezolid

Arm Intervention/treatment
Experimental: 1
Linezolid 600 mg po QD
Drug: Linezolid
600 mg po daily for 112 doses (16 weeks)
Other Name: Zyvox

Placebo Comparator: 2
Drug: Placebo
Placebo given daily for 112 doses (16 weeks)

Primary Outcome Measures :
  1. Cumulative rate of serious adverse events - SAEs (measured as the number of SAEs per person days) during the period of study therapy and the four weeks of post-study therapy follow-up. [ Time Frame: the period of study therapy (generally 16 weeks) plus the four weeks of post-study therapy follow-up. ]
  2. Proportion of patients in each arm who complete 80% of the proposed regimen (90 doses) within 18 weeks of treatment initiation. [ Time Frame: within 18 weeks of treatment initiation ]

Secondary Outcome Measures :
  1. The number of days required to convert to culture negative status in sputum of those in each treatment arm on solid and liquid media, respectively. [ Time Frame: first 16 weeks of study therapy ]
  2. The proportion of culture-negative patients during the first 16 weeks of therapy (at two week intervals) of linezolid with OBT vs. that of OBT with placebo on solid and liquid media, respectively [ Time Frame: first 16 weeks of study therapy ]
  3. Time to detection of M. tuberculosis on MGIT for each positive culture for sputum specimens collected every 2 weeks during the first 16 weeks of therapy [ Time Frame: First 16 weeks of study therapy ]
  4. The occurrence of treatment failure in the first 12 month following initiation of study therapy [ Time Frame: first 12 months ]
  5. Changes from baseline in assessments for peripheral neuropathy [ Time Frame: First 12 months ]
  6. Changes from baselines in Snellen or Jaeger visual acuity test and Ishihara color plate test results to assess for optic neuropathy [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  1. Pulmonary tuberculosis with or without extrapulmonary TB with a M. tuberculosis isolate that is confirmed to be resistant to at least rifampin and isoniazid (without regard to prior treatment for TB).
  2. A documented positive sputum culture result for M. tuberculosis from a sputum obtained in the four months prior to enrollment.
  3. 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.
  4. Residence within the Durban Functional Region (Durban Metropolitan Area) or Tugela Ferry, Msinga District, KZN, RSA.
  5. Age ≥ 18 years.
  6. Karnofsky score of > 50 (see section 18.1)
  7. Willingness by the patient to attend scheduled follow-up visits and undergo study assessments.
  8. Women with child-bearing potential must agree to practice an adequate method of birth control or to abstain from heterosexual intercourse during study therapy. (Standard birth control measures are provided free of charge by public health institutions)
  9. Laboratory parameters done within 14 days prior to screening:

    1. Serum creatinine level < 2 times upper limit of normal
    2. Hemoglobin level ≥ 9.0 g/dL
    3. Platelet count of ≥ 80,000/mm3
    4. Absolute neutrophil count (ANC) > 1000/ mm3
    5. Negative pregnancy test (for women of childbearing potential)
  10. Able to provide informed consent or legally authorized representative able to do so if decisionally impaired.

Exclusion Criteria

  1. Currently breast-feeding or pregnant.
  2. Known allergy or intolerance to linezolid.
  3. Planned therapy during the intensive phase of tuberculosis treatment using drugs having unacceptable interactions with linezolid, including dopamine, selective serotonin uptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), amitriptyline, bupropion, mirtazepine, levodopa, carbidopa, sinemet, or herbal medications.
  4. Significant peripheral neuropathy as evidenced by < 5 seconds of vibratory sense to a 128 Hz tuning fork on either big toe
  5. Pain, aching or burning of the feet that interfere with walking or sleep.
  6. In the judgment of the physician the patient is not expected to survive for more than 4 weeks.
  7. Anticipated surgical intervention for the treatment of pulmonary tuberculosis
  8. Visual acuity of 20/200 (6/60 meters) best corrected vision or less.
  9. Poor color vision as evidenced by incorrect answers on > four of 12 screening Ishihara plates
  10. Participation in another drug trial.
  11. The patient has received second line TB drugs for > 7 days immediately prior to enrollment (note: use of first line drugs such as INH, Rifampin, PZA, or ethambutol for > 7 days immediately prior to enrollment is allowed)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00664313

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South Africa
King George V Hospital
Durban, South Africa
Sponsors and Collaborators
Centers for Disease Control and Prevention
University of KwaZulu
Columbia University
Yale University
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Principal Investigator: Jussi Saukkonen, MD Boston University
Principal Investigator: Waffa El-Sadr, MD Columbia University
Principal Investigator: Nesri Padayachin, MBChB University of Kwa-Zulu Natal
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT00664313    
Other Study ID Numbers: CDC-NCHHSTP-5356
First Posted: April 22, 2008    Key Record Dates
Last Update Posted: October 2, 2012
Last Verified: October 2012
Keywords provided by Centers for Disease Control and Prevention:
Peripheral Neuropathy
Optic Neuropathy
Additional relevant MeSH terms:
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Tuberculosis, Multidrug-Resistant
Extensively Drug-Resistant Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action