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

NCT00664313 | Completed Phase 1 DMC

• 1 other identifier: CDC-NCHHSTP-5356
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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)

Conditions

Multi-drug Resistant Tuberculosis; Extensively Drug Resistant Tuberculosis

Keywords

Linezolid; Zyvox; Peripheral Neuropathy; Optic Neuropathy; Anemia; Thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• 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.

  the period of study therapy (generally 16 weeks) plus the four weeks of post-study therapy follow-up.

• Proportion of patients in each arm who complete 80% of the proposed regimen (90 doses) within 18 weeks of treatment initiation.

  within 18 weeks of treatment initiation

Secondary Outcomes (6)

• 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.

  first 16 weeks of study therapy

• 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

  first 16 weeks of study therapy

• 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

  First 16 weeks of study therapy

• The occurrence of treatment failure in the first 12 month following initiation of study therapy

  first 12 months

• Changes from baseline in assessments for peripheral neuropathy

  First 12 months

Study Arms (2)

Linezolid

EXPERIMENTAL

Linezolid 600 mg po QD

Drug: Linezolid

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Linezolid DRUG

600 mg po daily for 112 doses (16 weeks)

Also known as: Zyvox

Linezolid

Placebo DRUG

Placebo given daily for 112 doses (16 weeks)

Also known as: PH-102 Avicel (96%), Explotab sodium starch glycolate (3%), and Magnesium stearate (1%)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• University of KwaZulu: collaborator
• Columbia University: collaborator
• Yale University: collaborator

Study Sites (1)

King George V Hospital

Durban, South Africa

Location

Related Publications (1)

• Padayatchi N, Mac Kenzie WR, Hirsch-Moverman Y, Feng PJ, Villarino E, Saukkonen J, Heilig CM, Weiner M, El-Sadr WM. Lessons from a randomised clinical trial for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2012 Dec;16(12):1582-7. doi: 10.5588/ijtld.12.0315.

  PMID: 23131255 DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-Resistant; Extensively Drug-Resistant Tuberculosis; Peripheral Nervous System Diseases; Optic Nerve Diseases; Anemia; Thrombocytopenia

Interventions

Linezolid; stearic acid

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Neuromuscular Diseases; Nervous System Diseases; Cranial Nerve Diseases; Eye Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jussi Saukkonen, MD

  Boston University

  PRINCIPAL INVESTIGATOR

• Waffa El-Sadr, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

• Nesri Padayachin, MBChB

  University of Kwa-Zulu Natal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2008
• First Posted: April 22, 2008
• Study Start: April 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

ZA (1)