Trial Outcomes & Findings for The Evaluation of a Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB (NCT NCT02409290)
NCT ID: NCT02409290
Last Updated: 2023-09-28
Results Overview
The primary efficacy outcome of the STREAM Stage 2 comparison is status at Week 76 i.e. the proportion of patients with a favourable outcome at Week 76
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
588 participants
Primary outcome timeframe
76 weeks
Results posted on
2023-09-28
Participant Flow
Participants were assessed for eligibility from 13 hospital clinics in seven countries, and were randomised between March 2016 and January 2020
1436 participants were screened and 588 were randomly assigned to treatment.
Participant milestones
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
32
|
202
|
211
|
143
|
|
Overall Study
COMPLETED
|
0
|
187
|
196
|
134
|
|
Overall Study
NOT COMPLETED
|
32
|
15
|
15
|
9
|
Reasons for withdrawal
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Overall Study
Protocol Violation
|
3
|
6
|
9
|
4
|
|
Overall Study
No positive culture/no baseline sample
|
3
|
9
|
6
|
5
|
|
Overall Study
Completed but not analysed as recruitment stopped to this arm
|
26
|
0
|
0
|
0
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Regimen A (Long Regimen)
n=32 Participants
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=202 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=211 Participants
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=143 Participants
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
Total
n=588 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.0 years
n=32 Participants
|
32.8 years
n=202 Participants
|
32.8 years
n=211 Participants
|
30.8 years
n=143 Participants
|
32.7 years
n=588 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=32 Participants
|
81 Participants
n=202 Participants
|
79 Participants
n=211 Participants
|
59 Participants
n=143 Participants
|
236 Participants
n=588 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=32 Participants
|
121 Participants
n=202 Participants
|
132 Participants
n=211 Participants
|
84 Participants
n=143 Participants
|
352 Participants
n=588 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
Mongolia
|
11 participants
n=32 Participants
|
46 participants
n=202 Participants
|
48 participants
n=211 Participants
|
25 participants
n=143 Participants
|
130 participants
n=588 Participants
|
|
Region of Enrollment
South Africa
|
6 participants
n=32 Participants
|
28 participants
n=202 Participants
|
32 participants
n=211 Participants
|
26 participants
n=143 Participants
|
92 participants
n=588 Participants
|
|
Region of Enrollment
Uganda
|
0 participants
n=32 Participants
|
22 participants
n=202 Participants
|
25 participants
n=211 Participants
|
9 participants
n=143 Participants
|
56 participants
n=588 Participants
|
|
Region of Enrollment
Moldova
|
4 participants
n=32 Participants
|
25 participants
n=202 Participants
|
26 participants
n=211 Participants
|
8 participants
n=143 Participants
|
63 participants
n=588 Participants
|
|
Region of Enrollment
Georgia
|
0 participants
n=32 Participants
|
13 participants
n=202 Participants
|
12 participants
n=211 Participants
|
7 participants
n=143 Participants
|
32 participants
n=588 Participants
|
|
Region of Enrollment
Ethiopia
|
6 participants
n=32 Participants
|
21 participants
n=202 Participants
|
20 participants
n=211 Participants
|
20 participants
n=143 Participants
|
67 participants
n=588 Participants
|
|
Region of Enrollment
India
|
5 participants
n=32 Participants
|
47 participants
n=202 Participants
|
48 participants
n=211 Participants
|
48 participants
n=143 Participants
|
148 participants
n=588 Participants
|
PRIMARY outcome
Timeframe: 76 weeksPopulation: mITT population
The primary efficacy outcome of the STREAM Stage 2 comparison is status at Week 76 i.e. the proportion of patients with a favourable outcome at Week 76
Outcome measures
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=187 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=196 Participants
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=134 Participants
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
STREAM Stage 2 Primary Outcome Measure (the Proportion of Patients With a Favourable Outcome at Week 76)
|
0 Participants
|
133 Participants
|
162 Participants
|
122 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Last efficacy visit, between 96 and 132 weeksPopulation: mITT population, assessable patients
The proportion of patients with a favourable outcome at their last efficacy visit
Outcome measures
| Measure |
Regimen A (Long Regimen)
n=26 Participants
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=181 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=190 Participants
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=128 Participants
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Favourable Outcome After Long-term Follow-up (132 Weeks)
|
17 Participants
|
126 Participants
|
152 Participants
|
115 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 132 weeksPopulation: mITT population, excluding the long regimen (arm A)
The proportion of patients with acquired drug resistance (any drug)
Outcome measures
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=187 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=196 Participants
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=134 Participants
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Proportion of Patients With Acquired Drug Resistance
|
0 Participants
|
5 Participants
|
5 Participants
|
3 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: final efficacy week (between 96 and 132 weeks)Population: mITT population, comparing oral to control regimen
probable or definite failure or recurrence (FoR)
Outcome measures
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=187 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=196 Participants
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Failure or Recurrence (FoR)
|
0 Participants
|
17 Participants
|
4 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 132 weeks, control regimen (arm B) using concurrent controls onlyPopulation: mITT population, control regimen (arm B) using only concurrent controls
The proportion of patients with failure or recurrence (FoR)
Outcome measures
| Measure |
Regimen A (Long Regimen)
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=127 Participants
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=134 Participants
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Failure or Recurrence (FoR)
|
—
|
14 Participants
|
—
|
2 Participants
|
Adverse Events
Regimen A (Long Regimen)
Serious events: 8 serious events
Other events: 21 other events
Deaths: 0 deaths
Regimen B (Control Regimen)
Serious events: 44 serious events
Other events: 114 other events
Deaths: 8 deaths
Regimen C (Oral Regimen)
Serious events: 44 serious events
Other events: 109 other events
Deaths: 11 deaths
Regimen D (6-month Regimen)
Serious events: 33 serious events
Other events: 82 other events
Deaths: 2 deaths
Serious adverse events
| Measure |
Regimen A (Long Regimen)
n=32 participants at risk
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=202 participants at risk
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=211 participants at risk
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=143 participants at risk
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Ear and labyrinth disorders
Hearing and vestibular disorders (SMQ)
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.5%
7/202 • Number of events 7 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.3%
7/211 • Number of events 7 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.9%
7/143 • Number of events 7 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
General disorders
General disorders and administration site conditions
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.0%
6/202 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.95%
2/211 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.2%
6/143 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.5%
7/202 • Number of events 7 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.4%
5/211 • Number of events 5 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Investigations
Investigations
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.5%
3/202 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.9%
4/211 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.5%
5/143 • Number of events 5 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Hepatobiliary disorders
Hepatic disorders (SMQ)
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.5%
5/202 • Number of events 5 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.9%
4/211 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
6.2%
2/32 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.4%
5/211 • Number of events 5 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
3/211 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Surgical and medical procedures
Surgical and medical procedures
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.8%
6/211 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.9%
4/211 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Social circumstances
Social circumstances
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.95%
2/211 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Nervous system disorders
Nervous system disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Psychiatric disorders
Psychiatric disorders
|
6.2%
2/32 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Cardiac disorders
Torsade de pointes/QT prolongation (SMQ)
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Vascular disorders
Vascular disorders
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Cardiac disorders
Cardiac disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Congenital, familial and genetic disorders
Congenital, familial and genetic disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Infections and infestations
Infections and infestations
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
5.9%
12/202 • Number of events 12 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.3%
9/211 • Number of events 9 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
Other adverse events
| Measure |
Regimen A (Long Regimen)
n=32 participants at risk
Locally used regimen recommended by WHO in 2011
|
Regimen B (Control Regimen)
n=202 participants at risk
Regimen B is based on the regimen described by Van Deun 2010. With Version 8.0 of the protocol Regimen B (Regimen Bmox) is modified by replacement of moxifloxacin with levofloxacin (Regimen Blev). Regimen B without specification of which fluoroquinolone is in the regimen refers to either (Bmox or Blev).
Product and dose for \[\<33 kg, 33-50kg, \>50 kg\] respectively:
Moxifloxacin \[400mg, 600mg, 800mg\] OR Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg,100mg,100mg\]; Ethambutol \[800mg,800mg,1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid 300mg, 400mg, 600mg\]; Prothionamide \[250mg,500mg,750mg\]; Kanamycin \[15mg per kilogram body weight (maximum 1g)\].
|
Regimen C (Oral Regimen)
n=211 participants at risk
Regimen C is a 40-week all-oral regimen consisting of bedaquiline, clofazimine, ethambutol, levofloxacin, and pyrazinamide given for 40 weeks supplemented by isoniazid and prothionamide for the first 16 weeks (intensive phase).
Product and dose for \[\<33kg, 33-50kg, \>50 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200 mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg,1000mg\]; Clofazimine \[50mg, 100mg, 100mg\]; Ethambutol \[800mg, 800mg, 1200mg\]; Pyrazinamide \[1000mg,1500mg, 2000mg\]; Isoniazid \[300mg, 400mg, 600mg\]; Prothionamide \[250mg, 500mg,750mg\].
|
Regimen D (6-month Regimen)
n=143 participants at risk
Regimen D is a 28-week regimen consisting of bedaquiline, clofazimine, levofloxacin, and pyrazinamide given for 28 weeks supplemented by isoniazid and kanamycin for the first 8 weeks (intensive phase).
Product and dose for \[\<33kg, 33 to\<40kg, 40-50kg, \>50-60 kg, \>60 kg\] respectively:
Bedaquiline 400mg once daily for first 14 days/200mg thrice weekly thereafter; Levofloxacin \[750mg, 750mg, 750mg, 1000mg, 1000mg\]; Clofazimine \[50mg, 100mg, 100mg, 100mg, 100mg\]; Pyrazinamide \[1000mg,1500mg, 1500mg, 2000mg, 2000mg\]; Isoniazid \[400mg, 500mg, 600mg, 800mg, 900mg\]; Kanamycin \[15 mg per kilogram body weight (maximum 1g)\].
|
|---|---|---|---|---|
|
Cardiac disorders
Torsade de pointes/QT prolongation (SMQ)
|
6.2%
2/32 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
23.3%
47/202 • Number of events 47 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
24.6%
52/211 • Number of events 52 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
26.6%
38/143 • Number of events 38 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Hepatobiliary disorders
Hepatic disorders (SMQ)
|
9.4%
3/32 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
15.3%
31/202 • Number of events 31 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
15.6%
33/211 • Number of events 33 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
10.5%
15/143 • Number of events 15 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders
|
31.2%
10/32 • Number of events 10 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
10.9%
22/202 • Number of events 22 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
14.2%
30/211 • Number of events 30 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
14.0%
20/143 • Number of events 20 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Investigations
Investigations
|
31.2%
10/32 • Number of events 10 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
12.4%
25/202 • Number of events 25 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
9.0%
19/211 • Number of events 19 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
9.8%
14/143 • Number of events 14 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Ear and labyrinth disorders
Hearing and vestibular disorders (SMQ)
|
6.2%
2/32 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
9.9%
20/202 • Number of events 20 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.3%
9/211 • Number of events 9 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.2%
6/143 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
General disorders
General disorders and administration site conditions
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.5%
5/202 • Number of events 5 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.9%
4/211 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.2%
6/143 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.0%
4/202 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
3/211 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.2%
6/143 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Infections and infestations
Infections and infestations
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.0%
8/202 • Number of events 8 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
3/211 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Gastrointestinal disorders
Gastrointestinal disorders
|
9.4%
3/32 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.9%
4/211 • Number of events 4 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
3.5%
7/202 • Number of events 7 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.95%
2/211 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
2.1%
3/143 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
4.2%
6/143 • Number of events 6 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
|
6.2%
2/32 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Surgical and medical procedures
Surgical and medical procedures
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.95%
2/211 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Vascular disorders
Vascular disorders
|
3.1%
1/32 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.95%
2/211 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Nervous system disorders
Nervous system disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy, puerperium and perinatal conditions
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
1.4%
2/143 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Psychiatric disorders
Psychiatric disorders
|
9.4%
3/32 • Number of events 3 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Renal and urinary disorders
Renal and urinary disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.99%
2/202 • Number of events 2 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Cardiac disorders
Cardiac disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.50%
1/202 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Eye disorders
Eye disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.47%
1/211 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/143 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
|
Hepatobiliary disorders
Hepatobiliary disorders
|
0.00%
0/32 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/202 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.00%
0/211 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
0.70%
1/143 • Number of events 1 • 132 weeks
Adverse events reported include all Grade 3 and 4 events, which may overlap with the reporting of the Serious Adverse Events.
|
Additional Information
Dr Ruth Goodall
MRC CTU at UCL, University College London, London UK
Phone: +44 2076704728
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place