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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- 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.
研究概览
简要总结
This study evaluated the safety and tolerability of low-dose linezolid (600 mg once daily) administered for 16 weeks as part of an optimized background regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB).
详细描述
Tuberculosis Trials Consortium (TBTC) Study 30 was a randomized, double-blind, placebo-controlled Phase I/II clinical trial conducted to evaluate the safety and tolerability of low-dose linezolid when added to an optimized background regimen for the treatment of multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis.
Participants received either linezolid 600 mg orally once daily or matching placebo for 16 weeks in addition to background therapy consisting of at least four drugs with presumed activity against Mycobacterium tuberculosis.
The primary objectives were to assess tolerability, defined as the proportion of participants completing at least 80% of planned doses within 18 weeks, and safety, assessed by the occurrence of serious adverse events during treatment and a 4-week follow-up period.
Secondary assessments included adverse event profiles, laboratory safety parameters, and time to sputum culture conversion.
The study was conducted in Durban, South Africa, among adults with confirmed MDR or XDR tuberculosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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)
研究组 & 干预措施
Placebo
Placebo
干预措施: Placebo (Drug)
Linezolid
Linezolid 600 mg po QD
干预措施: Linezolid (Drug)
结局指标
主要结局
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.
时间窗: 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.
时间窗: within 18 weeks of treatment initiation
Participants Completing at Least 80% (≥90 of 112) of Assigned Study Drug Doses Within 18 Weeks
时间窗: 18 weeks
Proportion of participants who completed at least 80% (≥90 of 112 doses) of directly observed study drug within 18 weeks of treatment initiation.
Number of Serious Adverse Events During Study Drug Therapy and 4 Weeks Post-Therapy
时间窗: 20 weeks
Number of serious adverse events occurring during study drug therapy and the 4 weeks after completion of study therapy.
次要结局
- 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)
- Changes from baselines in Snellen or Jaeger visual acuity test and Ishihara color plate test results to assess for optic neuropathy(12 months)