Clinical trial NCT05555303: Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Tuberculosis, Multidrug-Resistant
Keywords: multidrug- and rifampicin-resistant tuberculosis
Lead sponsor: Rwanda Biomedical Centre
Sponsor class: OTHER
Collaborators: name: Institute of Tropical Medicine
name: World Health Organization
First posted: 2022-09-26
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: grade 3-4 AE likely or definitively related to amikacin
timeFrame: After 2 weeks of treatment
Secondary outcomes:
measure: turnaround times
timeFrame: at the end of treatment week 2 (+/- 3 d)
measure: testing coverage
timeFrame: at the end of treatment week 2 (+/- 3 d)
measure: AE likely or definitely related to amikacin
timeFrame: at the end of treatment week 2 (+/- 3 d)
measure: amikacin concentration
timeFrame: during the first two treatment weeks
measure: amikacin concentration
timeFrame: during the first two treatment weeks
measure: amikacin concentration
timeFrame: during the first two treatment weeks
measure: amikacin concentration
timeFrame: during the first two treatment weeks
measure: amikacin concentration
timeFrame: during the first two treatment weeks
measure: post-injection pain
timeFrame: 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
measure: all AE, relationship with TB drugs
timeFrame: at the end of the ShORRT study, approximately 23 months after the treatment
measure: treatment outcomes
timeFrame: at the end of treatment
measure: post-treatment outcomes
timeFrame: after post-treatment follow-up (part of ShORRT analysis)
Other outcomes:
Locations:
city: Kabutare
country: Rwanda
facility: Kabutare hospital
Study officials:
affiliation: Rwanda Biomedical Centre
name: Yves Habimana-Mucyo, MSc
role: PRINCIPAL_INVESTIGATOR
References: