Rapid Detection of Rifampin and Isoniazid Resistance by PCR Before Tuberculosis (TB) Treatment Initiation: a National Multicenter Randomized Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 204
- 试验地点
- 2
- 主要终点
- Proportion of patients with treatment success at the end of TB treatment
研究概览
简要总结
French guidelines currently recommend to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings.
the duration of treatment is 6 months or 12 months.
详细描述
The impact of rapid detection of resistance with PCR has been poorly evaluated in low-endemic countries. In France, primary resistance to isoniazid and rifampicin were estimated at, respectively, 5.2%, and 1.2 %. Based on these estimates, French guidelines currently recommends to initiate a 4-drug containing regimen associating isoniazid (INH or H), rifampicin (RIFor RMP or R), pyrazinamide (PZA or Z) and ethambutol (EMB or E) pending the results of drug susceptibility testing (DST). The rationale behind routine use of EMB is to prevent the emergence of resistance to rifampicin (RMP), in case of primary resistance to INH. Hence, early detection of resistance to INH and RIF using molecular testing in Mycobacterium tuberculosis could allow early adaptation of antituberculosis treatment: i) start with a 3-drug containing regimen (i.e. INH, RIF, and PZA), in patients with fully susceptible isolates (currently 95% of cases); ii) early enforcement of treatment when resistance is suspected, pending in depth susceptibility testings. GenoType ®MTB DR plus sensitivity for RIF and INH resistance detection has been estimated at 100% and 83%, respectively.
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
- None
入排标准
- 年龄范围
- 18 Years 至 84 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients
- •with active pulmonary tuberculosis (TB) and positive respiratory samples on microscopic examination for acid-fast bacilli (AFB+,) who are eligible for a standard TB treatment with a 4 drug combination
- •PCR (Genotype MTBDR Plus v2.0, Hain Lifescience) result available within the first 7 days of tuberculosis treatment.
- •who are seeking care in France (metropolitan or overseas) and accept a follow-up of 18 to 24 months after inclusion.
- •who have had a prior clinical examination
排除标准
- •Refusal to participate in the study
- •Prior history of TB treatment
- •For women of child bearing age, pregnancy, willing to become pregnant or breastfeeding
- •Patient without healthcare insurance (French social security)
- •Patient participating in another clinical trial
- •Any condition that might compromise, in the investigator's opinion, patient's compliance with the protocol.
- •Results of cultures available at enrollment
- •No HIV testing available within the last 3 months prior to inclusion in the study.
研究组 & 干预措施
PCR-based strategy
PCR-based strategy: after testing for isoniazid and rifampin resistance using a molecular testing with PCR (GenoType ®MTB DR plus), patients will receive HRZ combination therapy (INH , RIF, PZA) if no resistance is detected
干预措施: PCR-based strategy (Other)
conventional therapy
Conventional therapy: based on the standard of care in France: initiation of the standard 4 drug regimen INH, RIF, PZA, and EMB, until drug susceptibility testing (DST) results are available.
干预措施: conventional therapy (Drug)
结局指标
主要结局
Proportion of patients with treatment success at the end of TB treatment
时间窗: 6 or 12 months after enrollment
TB treatment success (cure certain or probable cure) at the end of TB treatment * cure certain: negative sputum cultures or negative sputum direct examination in a patient who has completed treatment and have never filled the definition of treatment failure. * probable cure: clinical and radiological improvement of symptoms associated with tuberculosis in a patient who has completed treatment and have never filled the definition of treatment failure. * completed treatment: patients who took more than 80% of prescribed treatment. * clinical improvement: improvement in overall score of Teeter AND no weight loss * radiological improvement: between baseline and end of treatment * failure: if Positive sputum culture after 5 months of treatment, death during treatment whatever the cause, treatment interrupted for more than two months, decision of the clinician to change TB treatment because of the suspicion of failure after 5 months of TB treatment
次要结局
- Proportion of patients with failure(6 or 12 months after enrollment)
- Capillary drug concentration, for each of the prescribed treatment in hair segments(at 2 and 6 months)
- Incidence and nature of grade 3 or grade 4 adverse events related or not to TB treatments(6 months or at the latest 12 months after enrollment)
- Direct medical costs associated with each strategy(within 18 or at the latest 12 months after enrolment)
- Proportion of patients with relapse(within 12 months after the end of TB treatment)