Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis (Stake)

Rwanda Biomedical Centre

Status and phase

Enrolling

Phase 2

Conditions

Tuberculosis, Multidrug-Resistant

Treatments

Drug: Amikacin

Study type

Interventional

Funder types

Other

Identifiers

NCT05555303

RBC/RIDS012022

Details and patient eligibility

About

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).

Enrollment

20 estimated patients

Sex

All

Ages

19 to 64 years old

Volunteers

No Healthy Volunteers

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.