Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis (Stake) Amendment to Study Protocol: "All-oral Shorter Treatment Regimen for Multidrug- and Rifampicin-resistant Tuberculosis (MDR/RR-TB): Evaluating Its Effectiveness, Safety and Impact on the Quality of Life of Patients in Rwanda" (ShORRT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- grade 3-4 AE likely or definitively related to amikacin
研究概览
简要总结
Acquired drug-resistance is a major challenge for tuberculosis (TB) care programs. The 2020 WHO guidelines recommends replacing second-line injectables by bedaquiline in rifampicin-resistant TB (RR-TB) treatment regimens. However, recent reports show too high rates of acquired bedaquiline resistance. This may be explained by the delayed onset of action of bedaquiline. The investigators will study whether high-dose amikacin (a second-line injectable), administered during the first week of RR-TB treatment, is safe in 20 patients treated for RR-TB in Rwanda. If safe, further studies will assess whether adding amikacin in the first treatment week protect against acquired bedaquiline resistance. This study is embedded in an ongoing "Master study" of the ShORRT (short oral RR-TB) treatment regimen in Rwanda, a before/after study, with a retrospective cohort (before; the previously recommended second-line injectable-containing RR-TB regimen) and a prospective cohort (after: the newly recommended ShORRT regimen).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Enrolled in the Master SHORRT study
- •Able and willing to provide written informed consent for the present substudy "Stake"
排除标准
- •Any audiometry abnormality (grade 1 or higher) on baseline audiometry
- •History of kidney disease or baseline creatinine clearance below or equal to 60ml/min
- •Pregnant or breastfeeding women
- •History of previous injectable based tuberculosis treatment (including with streptomycin)
- •< 18 years and > 65 years old
- •Patient on NSAID or on diuretics
- •Master ShORRT study
- •Inclusion criteria:
- •Is willing and able to give informed consent to be enrolled in the research project and for follow-up
- •Has bacteriologically or molecularly confirmed TB with evidence of resistance to at least rifampicin
- •Exclusion criteria:
- •Is unable to take oral medication;
- •Must take any medications contraindicated with the medicines in the MDR/RR-TB regimen;
- •Has a known allergy to any of the drugs in the MDR/RR-TB regimen;
- •Has a QTcF interval of ≥ 500 msec; at baseline that does not correct with medical management.
研究组 & 干预措施
Amikacin
干预措施: Amikacin (Drug)
结局指标
主要结局
grade 3-4 AE likely or definitively related to amikacin
时间窗: After 2 weeks of treatment
Assess whether less than 14% of patients treated with the amikacin-strengthened regimen will experience a grade 3-4 adverse event likely or definitively related to the use of amikacin
次要结局
- post-injection pain(at 0, 15 minutes, 30 minutes and 60 minutes after the injection of amikacin with lidocaine on day 1 and 4, as well as the next morning)
- all AE, relationship with TB drugs(at the end of the ShORRT study, approximately 23 months after the treatment)
- treatment outcomes(at the end of treatment)
- post-treatment outcomes(after post-treatment follow-up (part of ShORRT analysis))
- turnaround times(at the end of treatment week 2 (+/- 3 d))
- testing coverage(at the end of treatment week 2 (+/- 3 d))
- AE likely or definitely related to amikacin(at the end of treatment week 2 (+/- 3 d))
- amikacin concentration(during the first two treatment weeks)