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)

RBC/RIDS012022

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).

2023-03-01

2024-03-01

2026-02-01

Recruiting

Early phase I

20

Inclusion Criteria: * Enrolled in the Master SHORRT study * Able and willing to provide written informed consent for the present substudy "Stake" Exclusion Criteria: * 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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2023-03-29