Back to resultsPreventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis (Stake)
Primary Purpose
Tuberculosis, Multidrug-Resistant
Status
Recruiting
Phase
Phase 2
Locations
Rwanda
Study Type
Interventional
Intervention
Amikacin
Sponsored by
About this trial
This is an interventional treatment trial for Tuberculosis, Multidrug-Resistant focused on measuring multidrug- and rifampicin-resistant tuberculosis
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.
Sites / Locations
- Kabutare hospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Amikacin
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
testing coverage
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
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
amikacin concentration
Describe the amikacin concentration stratified by values for different treatment response markers : Colony forming units on semi-quantitative culture
amikacin concentration
Describe the amikacin concentration stratified by values for different treatment response markers : molecular bacterial load
amikacin concentration
Describe the amikacin concentration stratified by values for different treatment response markers : thin-layer agar semi-quantitative culture
amikacin concentration
Describe the amikacin concentration stratified by values for different treatment response markers: RNA Synthesis ratio
amikacin concentration
Describe the amikacin concentration stratified by values for different treatment response markers : time to culture positivity on liquid culture
post-injection pain
Describe post-injection pain on a 0-10 pain scale (The Wong-Baker FACES pain rating scale) (15)
all AE, relationship with TB drugs
Describe all AE, by their grade, and their relationship with TB drugs
treatment outcomes
Describe treatment outcomes, using the following effectiveness endpoints:
Month of stable (without reversion) culture conversion
End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa
post-treatment outcomes
Describe post-treatment outcomes, using the following effectiveness endpoints:
Month of stable (without reversion) culture conversion
End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa
Full Information
NCT ID
NCT05555303
First Posted
September 16, 2022
Last Updated
March 24, 2023
Sponsor
Rwanda Biomedical Centre
Collaborators
Institute of Tropical Medicine, World Health Organization
1. Study Identification
Unique Protocol Identification Number
NCT05555303
Brief Title
Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis
Acronym
Stake
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
February 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rwanda Biomedical Centre
Collaborators
Institute of Tropical Medicine, World Health Organization
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Tuberculosis, Multidrug-Resistant
Keywords
multidrug- and rifampicin-resistant tuberculosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Amikacin
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
Amikacin
Intervention Description
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.
Primary Outcome Measure Information:
Title
grade 3-4 AE likely or definitively related to amikacin
Description
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
Time Frame
After 2 weeks of treatment
Secondary Outcome Measure Information:
Title
turnaround times
Description
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
Time Frame
at the end of treatment week 2 (+/- 3 d)
Title
testing coverage
Description
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
Time Frame
at the end of treatment week 2 (+/- 3 d)
Title
AE likely or definitely related to amikacin
Description
Describe the occurrence of adverse events that are considered as likely or definitely related to the use of amikacin
Time Frame
at the end of treatment week 2 (+/- 3 d)
Title
amikacin concentration
Description
Describe the amikacin concentration stratified by values for different treatment response markers : Colony forming units on semi-quantitative culture
Time Frame
during the first two treatment weeks
Title
amikacin concentration
Description
Describe the amikacin concentration stratified by values for different treatment response markers : molecular bacterial load
Time Frame
during the first two treatment weeks
Title
amikacin concentration
Description
Describe the amikacin concentration stratified by values for different treatment response markers : thin-layer agar semi-quantitative culture
Time Frame
during the first two treatment weeks
Title
amikacin concentration
Description
Describe the amikacin concentration stratified by values for different treatment response markers: RNA Synthesis ratio
Time Frame
during the first two treatment weeks
Title
amikacin concentration
Description
Describe the amikacin concentration stratified by values for different treatment response markers : time to culture positivity on liquid culture
Time Frame
during the first two treatment weeks
Title
post-injection pain
Description
Describe post-injection pain on a 0-10 pain scale (The Wong-Baker FACES pain rating scale) (15)
Time Frame
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
Title
all AE, relationship with TB drugs
Description
Describe all AE, by their grade, and their relationship with TB drugs
Time Frame
at the end of the ShORRT study, approximately 23 months after the treatment
Title
treatment outcomes
Description
Describe treatment outcomes, using the following effectiveness endpoints:
Month of stable (without reversion) culture conversion
End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa
Time Frame
at the end of treatment
Title
post-treatment outcomes
Description
Describe post-treatment outcomes, using the following effectiveness endpoints:
Month of stable (without reversion) culture conversion
End-of-treatment outcomes (treatment failure, death during treatment, LTFU during treatment, cure, treatment completion)
Treatment outcomes at 12 months post-treatment (end-of treatment outcome corrected for relapse)
Acquired resistance to bedaquiline, fluoroquinolone, amikacin through target deep sequencing on paired baseline and failure sputa
Time Frame
after post-treatment follow-up (part of ShORRT analysis)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yves Habimana-Mucyo, MSc
Phone
+250733436765
Email
yves.mucyo@rbc.gov.rw
First Name & Middle Initial & Last Name or Official Title & Degree
Jean Claude S. NGABONZIZA, PhD
Phone
+250788740490
Email
jclaude.ngabonziza@rbc.gov.rw
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yves Habimana-Mucyo, MSc
Organizational Affiliation
Rwanda Biomedical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kabutare hospital
City
Kabutare
Country
Rwanda
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Habimana-Mucyo, MSc
Phone
+250733436765
Email
yves.mucyo@rbc.gov.rw
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Preventing Acquired Resistance: Strengthen TB Treatment by Adding Amikacin in the First Treatment Week of Multidrug-resistant Tuberculosis
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