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

NCT ID: NCT00664313

Last Updated: 2025-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2010-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Linezolid

Linezolid 600 mg po QD

Group Type: EXPERIMENTAL

Linezolid

Intervention Type: DRUG

600 mg po daily for 112 doses (16 weeks)

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo given daily for 112 doses (16 weeks)

Interventions

Linezolid

600 mg po daily for 112 doses (16 weeks)

Intervention Type: DRUG

Placebo

Placebo given daily for 112 doses (16 weeks)

Intervention Type: DRUG

Other Intervention Names

Zyvox; PH-102 Avicel (96%), Explotab sodium starch glycolate (3%), and Magnesium stearate (1%)

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of KwaZulu

OTHER

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jussi Saukkonen, MD

Role: PRINCIPAL_INVESTIGATOR

Boston University

Waffa El-Sadr, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Nesri Padayachin, MBChB

Role: PRINCIPAL_INVESTIGATOR

University of Kwa-Zulu Natal

Locations

King George V Hospital

Durban, , South Africa

Countries

South Africa

References

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.

Reference Type: DERIVED

PMID: 23131255 (View on PubMed)

Other Identifiers

CDC-NCHHSTP-5356

Identifier Type: -

Identifier Source: org_study_id

NCT00691392

Identifier Type: -

Identifier Source: nct_alias