TBTC Study 30: Safety and Tolerability of Low Dose Linezolid in MDR TB - Full Text View

Sponsor:	Centers for Disease Control and Prevention
Collaborators:	University of KwaZulu Columbia University Yale University
Information provided by:	Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:	NCT00664313

Purpose

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	Intervention	Phase
Multi-drug Resistant Tuberculosis Extensively Drug Resistant Tuberculosis	Drug: Linezolid Drug: Placebo	Phase I Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

MedlinePlus related topics: Tuberculosis

Drug Information available for: Linezolid

U.S. FDA Resources

Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:

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. ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
The occurrence of treatment failure in the first 12 month following initiation of study therapy [ Time Frame: first 12 months ] [ Designated as safety issue: No ]
Changes from baseline in assessments for peripheral neuropathy [ Time Frame: First 12 months ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Enrollment:	36
Study Start Date:	April 2009
Study Completion Date:	September 2010
Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Linezolid 600 mg po QD	Drug: Linezolid 600 mg po daily for 112 doses (16 weeks) Other Name: Zyvox
Placebo Comparator: 2 Placebo	Drug: Placebo Placebo given daily for 112 doses (16 weeks)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

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).
A documented positive sputum culture result for M. tuberculosis from a sputum obtained in the four months prior to enrollment.
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.
Residence within the Durban Functional Region (Durban Metropolitan Area) or Tugela Ferry, Msinga District, KZN, RSA.
Age ≥ 18 years.
Karnofsky score of > 50 (see section 18.1)
Willingness by the patient to attend scheduled follow-up visits and undergo study assessments.
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)
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)
Able to provide informed consent or legally authorized representative able to do so if decisionally impaired.

Exclusion Criteria

Currently breast-feeding or pregnant.
Known allergy or intolerance to linezolid.
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.
Significant peripheral neuropathy as evidenced by < 5 seconds of vibratory sense to a 128 Hz tuning fork on either big toe
Pain, aching or burning of the feet that interfere with walking or sleep.
In the judgment of the physician the patient is not expected to survive for more than 4 weeks.
Anticipated surgical intervention for the treatment of pulmonary tuberculosis
Visual acuity of 20/200 (6/60 meters) best corrected vision or less.
Poor color vision as evidenced by incorrect answers on > four of 12 screening Ishihara plates
Participation in another drug trial.
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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00664313

Locations

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

Investigators

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

More Information

No publications provided

Responsible Party:	William R. Mac Kenzie, MD, CDC TBTC Project Officer, Tuberculosis Trials Consortium, CDC
ClinicalTrials.gov Identifier:	NCT00664313 History of Changes
Other Study ID Numbers:	CDC-NCHSTP-5356
Study First Received:	April 18, 2008
Last Updated:	June 7, 2011
Health Authority:	United States: Food and Drug Administration; South Africa: Medicines Control Council

Keywords provided by Centers for Disease Control and Prevention:

Linezolid
Zyvox
Peripheral Neuropathy

Optic Neuropathy
Anemia
Thrombocytopenia

Additional relevant MeSH terms:

Tuberculosis
Tuberculosis, Multidrug-Resistant
Extensively Drug-Resistant Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

Linezolid
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012