Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis
Stake
1 other identifier
interventional
20
1 country
1
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Mar 2023
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 16, 2022
CompletedFirst Posted
Study publicly available on registry
September 26, 2022
CompletedStudy Start
First participant enrolled
March 1, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
February 1, 2026
CompletedMarch 29, 2023
March 1, 2023
1 year
September 16, 2022
March 24, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
grade 3-4 AE likely or definitively related to amikacin
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
After 2 weeks of treatment
Secondary Outcomes (12)
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
amikacin concentration
during the first two treatment weeks
- +7 more secondary outcomes
Study Arms (1)
Amikacin
OTHERInterventions
In addition to the all-oral RR-TB treatment, add two intramuscular doses each consisting of 30 mg amikacin/kg, a first dose on day 1 and a second dose on day 4, all in the first week of treatment. The amikacin solution will be admixed with a lidocaine solution in the syringe before administration.
Eligibility Criteria
You may qualify if:
- Enrolled in the Master SHORRT study
- Able and willing to provide written informed consent for the present substudy "Stake"
You may not qualify if:
- 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
- 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
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Rwanda Biomedical Centrelead
- Institute of Tropical Medicinecollaborator
- World Health Organizationcollaborator
Study Sites (1)
Kabutare hospital
Kabutare, Rwanda
Related Publications (1)
Snobre J, Gasana J, Ngabonziza JCS, Cuella-Martin I, Rigouts L, Jacobs BK, de Viron E, Herssens N, Ntihumby JB, Klibazayre A, Ndayishimiye C, Van Deun A, Affolabi D, Merle CS, Muvunyi C, Sturkenboom MGG, Migambi P, de Jong BC, Mucyo Y, Decroo T. Safety of high-dose amikacin in the first week of all-oral rifampicin-resistant tuberculosis treatment for the prevention of acquired resistance (STAKE): protocol for a single-arm clinical trial. BMJ Open. 2024 Jul 24;14(7):e078379. doi: 10.1136/bmjopen-2023-078379.
PMID: 39053960DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yves Habimana-Mucyo, MSc
Rwanda Biomedical Centre
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 16, 2022
First Posted
September 26, 2022
Study Start
March 1, 2023
Primary Completion
March 1, 2024
Study Completion
February 1, 2026
Last Updated
March 29, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will not share