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| Name | Class |
|---|---|
| Institute of Tropical Medicine | OTHER_GOV |
| World Health Organization | OTHER |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Amikacin | Other |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Amikacin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| turnaround times | Assess the turnaround times to inform the feasibility of doing the tests proposed in this study for the assessment of the response to the use of two doses of amikacin | at the end of treatment week 2 (+/- 3 d) |
| testing coverage |
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Inclusion Criteria:
Exclusion Criteria:
Master ShORRT study
Inclusion criteria:
Exclusion criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yves Habimana-Mucyo, MSc | Contact | +250733436765 | yves.mucyo@rbc.gov.rw | |
| Jean Claude S. NGABONZIZA, PhD | Contact | +250788740490 | jclaude.ngabonziza@rbc.gov.rw |
| Name | Affiliation | Role |
|---|---|---|
| Yves Habimana-Mucyo, MSc | Rwanda Biomedical Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kabutare hospital | Recruiting | Kabutare | Rwanda |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39053960 | Derived | 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. |
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| ID | Term |
|---|---|
| D018088 | Tuberculosis, Multidrug-Resistant |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
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| ID | Term |
|---|---|
| D000583 | Amikacin |
| ID | Term |
|---|---|
| D007612 | Kanamycin |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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|
Assess the testing coverage (proportion of patients with a result for each of the tests) to inform the feasibility of doing the tests proposed in this study for the assessment of the response to the use of two doses of amikacin
| at the end of treatment week 2 (+/- 3 d) |
| AE likely or definitely related to amikacin | Describe the occurrence of adverse events that are considered as likely or definitely related to the use of amikacin | at the end of treatment week 2 (+/- 3 d) |
| amikacin concentration | Describe the amikacin concentration stratified by values for different treatment response markers : Colony forming units on semi-quantitative culture | during the first two treatment weeks |
| amikacin concentration | Describe the amikacin concentration stratified by values for different treatment response markers : molecular bacterial load | during the first two treatment weeks |
| amikacin concentration | Describe the amikacin concentration stratified by values for different treatment response markers : thin-layer agar semi-quantitative culture | during the first two treatment weeks |
| amikacin concentration | Describe the amikacin concentration stratified by values for different treatment response markers: RNA Synthesis ratio | during the first two treatment weeks |
| amikacin concentration | Describe the amikacin concentration stratified by values for different treatment response markers : time to culture positivity on liquid culture | during the first two treatment weeks |
| post-injection pain | Describe post-injection pain on a 0-10 pain scale (The Wong-Baker FACES pain rating scale) (15) | 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 | Describe all AE, by their grade, and their relationship with TB drugs | at the end of the ShORRT study, approximately 23 months after the treatment |
| treatment outcomes | Describe treatment outcomes, using the following effectiveness endpoints:
| at the end of treatment |
| post-treatment outcomes | Describe post-treatment outcomes, using the following effectiveness endpoints:
| after post-treatment follow-up (part of ShORRT analysis) |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |