Linezolid to Treat Extensively-Drug Resistant Tuberculosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Clifton E. Barry III, Ph.D., National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00727844
First received: August 1, 2008
Last updated: February 21, 2014
Last verified: February 2014
Results First Received: September 10, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Pulmonary Tuberculosis
Multidrug Resistant Tuberculosis
Extensively Drug Resistant Tuberculosis
Interventions: Drug: Immediate Start Linezolid
Drug: Delayed Start Linezolid

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study patients recruited from 12/2008 to 5/2011 at the National Masan Hospital, Changwon, Korea and the National Medical Center, Seoul, Korea.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Initial Randomization: Immediate Start Linezolid Upon completion of entry criteria, subjects immediately added linezolid 600 mg once daily to their ongoing TB treatment regimen.
Initial Randomization: Delayed Start Linezolid Subjects continued their existing treatment regimen for 2 additional months after which linezolid 600 mg once daily was added.
2nd Randomization: Linezolid 600 mg Daily After conversion to negative sputum smears (or receipt of 4 months of therapy), patients underwent a second randomization, stratified according to diabetes mellitus status, either to continue receiving linezolid at a dose of 600 mg per day or to receive a lower dose, 300 mg per day, for an additional 18 months or until therapy was stopped owing to side effects or laboratory abnormalities.
2nd Randomization: Linezolid 300 mg Daily After conversion to negative sputum smears (or receipt of 4 months of therapy), patients underwent a second randomization, stratified according to diabetes mellitus status, either to continue receiving linezolid at a dose of 600 mg per day or to receive a lower dose, 300 mg per day, for an additional 18 months or until therapy was stopped owing to side effects or laboratory abnormalities.

Participant Flow for 2 periods

Period 1:   Initial Randomization
    Initial Randomization: Immediate Start Linezolid     Initial Randomization: Delayed Start Linezolid     2nd Randomization: Linezolid 600 mg Daily     2nd Randomization: Linezolid 300 mg Daily  
STARTED     21 [1]   20     0     0  
Included in MITT Analysis     19     20     0     0  
COMPLETED     19     20     0     0  
NOT COMPLETED     2     0     0     0  
Physician Decision                 2                 0                 0                 0  
[1] 2 patients withdrawn before receiving any linezolid owing to baseline neuropathy

Period 2:   Second Randomization
    Initial Randomization: Immediate Start Linezolid     Initial Randomization: Delayed Start Linezolid     2nd Randomization: Linezolid 600 mg Daily     2nd Randomization: Linezolid 300 mg Daily  
STARTED     0     0     17 [1]   16 [1]
COMPLETED     0     0     17     16  
NOT COMPLETED     0     0     0     0  
[1] 6 patients excluded before 2nd randomization: 2 had withdrawn and 4 already dose reduced due to AE



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
2 patients excluded in immediate start group before receiving any linezolid owing to baseline neuropathy

Reporting Groups
  Description
Immediate Start Linezolid Upon completion of entry criteria, subjects will have LZD (600 mg once daily) added to their regimen. After 2 consecutive AFB negative sputum smears (or at 4 months) subjects will be randomized to continue on 600 mg LZD once daily or to de-escalate to 300 mg once daily. Regardless of the dosage, subjects will remain on LZD treatment for 18 months after sputum culture conversion or until they can no longer tolerate therapy.
Delayed Start Linezolid Subjects will continue their existing regimen for 2 months after which LZD (600 mg once daily) will be added. After 2 consecutive AFB negative sputum smears (not to exceed 4 months of LZD therapy), subjects will be randomized to continue on 600 mg LZD once daily or to de-escalate to 300 mg once daily. Regardless of the dosage, subjects will remain on LZD treatment for 18 months after sputum culture conversion or until they can no longer tolerate therapy.
Total Total of all reporting groups

Baseline Measures
    Immediate Start Linezolid     Delayed Start Linezolid     Total  
Number of Participants  
[units: participants]
  19     20     39  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     19     20     39  
>=65 years     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  42.1  ± 11.2     40.4  ± 9.8     41.2  ± 10.4  
Gender  
[units: participants]
     
Female     7     4     11  
Male     12     16     28  
Region of Enrollment  
[units: participants]
     
Korea, Republic of     19     20     39  



  Outcome Measures

1.  Primary:   Number of Patients Converted to Sputum Culture Negative in Each Arm, With Data Censored at 4 Months.   [ Time Frame: Sputum smear conversion or max 4 months after the start of Linezolid therapy. ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Small sample size  


Results Point of Contact:  
Name/Title: Dr. Clifton Barry
Organization: Tuberculosis Research Section, LCID, NIAID, NIH
phone: 301-451-9554
e-mail: cbarry@niaid.nih.gov


Publications of Results:
Other Publications:

Responsible Party: Clifton E. Barry III, Ph.D., National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00727844     History of Changes
Other Study ID Numbers: 08-I-N167
Study First Received: August 1, 2008
Results First Received: September 10, 2013
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration