Study: NCT04310930

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Tigecycline
Description: Adults: Intravenous Tigecycline 25 mg increasing by 5 mg every two doses until either maximum dose reached (50mg) or until patient is unable to tolerate twice daily. Children (≥8 years of age) intravenous tigecycline: Day 1- 0.6mg/kg twice daily to a maximum of 25mg. Day 2- 0.6mg/kg (maximum 25mg) in the morning, 1.2 mg/kg (maximum 50mg) at night. Day 3- 1.2mg/kg (maximum 50 mg) twice daily

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Imipenem
Description: Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (\<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Imipenem
Description: Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (\<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Imipenem
Description: Adults: Intravenous Imipenem (≥50kg) 500mg twice daily (\<50kg) 15 mg/kg twice daily. Children: intravenous imipenem Day 1- 2- 25mg/kg (maximum 1g) twice daily. DAY 3- 25mg/kg (maximum 1g) four times daily (drop to 3 if not tolerated).

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Cefoxitin
Description: Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cefoxitin
Description: Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Cefoxitin
Description: Adults: If imipenem is poorly tolerated intravenous cefoxitin 200 mg/kg thrice daily. Children: if imipenem is poorly tolerated intravenous cefoxitin 50mg/kg (maximum 4g) four times daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Azithromycin
Description: Adults: Oral azithromycin 500mg (≥40kg) once daily, (\<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (\<40kg) 250mg thrice weekly.~Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azithromycin
Description: Adults: Oral azithromycin 500mg (≥40kg) once daily, (\<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (\<40kg) 250mg thrice weekly.~Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Azithromycin
Description: Adults: Oral azithromycin 500mg (≥40kg) once daily, (\<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (\<40kg) 250mg thrice weekly.~Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azithromycin
Description: Adults: Oral azithromycin 500mg (≥40kg) once daily, (\<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (\<40kg) 250mg thrice weekly.~Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Azithromycin
Description: Adults: Oral azithromycin 500mg (≥40kg) once daily, (\<40kg) 250mg once daily.During consolidaiton: 500mg (≥40kg) thrice weekly, (\<40kg) 250mg thrice weekly.~Children: Oral azithromycin:10mg/kg (maximum 500mg) once daily. During consolidation 10mg/kg once daily maximum 500mg.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Clarithromycin
Description: Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: \<8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Clarithromycin
Description: Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: \<8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Clarithromycin
Description: Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: \<8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Clarithromycin
Description: Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: \<8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Clarithromycin
Description: Adult: If azithromycin is poorly tolerated use oral clarithromycin 500mg twice daily.Children: If azithromycin is poorly tolerated use oral clarithromycin. In children 1 month old- 11years of age the following dosing applies: \<8kg: 7.5mg/kg twice daily, maximum dose 62.5mg, 8-11kg: 62.5mg twice daily, maximum dose 62.5mg, 12-19 kg: 125mg twice daily, maximum dose 125mg, 20-29 kg: 187.5mg twice daily, maximum dose 187.5mg, 30-40 kg: 250mg twice daily, maximum dose 250mg, Children 12-18 years of age: 500 mg twice daily

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Clofazimine
Description: Adult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if \<40kg or 100mg if ≥40kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Clofazimine
Description: Adult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if \<40kg or 100mg if ≥40kg once daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Clofazimine
Description: Adult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if \<40kg or 100mg if ≥40kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Clofazimine
Description: Adult: Oral clofazimine 100mg once daily. Children: Oral clofazimine: 3-5mg/kg once daily. Maximum dose of 50mg once daily if \<40kg or 100mg if ≥40kg once daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Ethambutol
Description: Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ethambutol
Description: Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Ethambutol
Description: Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ethambutol
Description: Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Ethambutol
Description: Adults: with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at either 15 mg/kg once daily or 25mg/kg thrice weekly. Children with confirmed mixed NTM infections (slow growers + MABS) oral ethambutol can be added at 20 mg/kg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Amikacin
Description: adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Amikacin
Description: adult: Inhaled amikacin 500mg twice daily. Children: Inhaled amikacin 500mg twice daily

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Linezolid
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily.~Children: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Age 1 week - 9 years 10mg/kg twice daily maximum dose of 300mg. Age 10-12 years 10mg/kg twice daily maximum dose of 600mg. \>12 years 600mg once daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Linezolid
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral linezolid 600mg once daily.~Children: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Age 1 week - 9 years 10mg/kg twice daily maximum dose of 300mg. Age 10-12 years 10mg/kg twice daily maximum dose of 600mg. \>12 years 600mg once daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: co-trimoxazole
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral Co-trimoxazole (TMP-SMX) 160/800mg twice daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral co-trimoxazole 5mg TMP/kg maximum dose of 160mg TMP/ 800mg SMX twice daily.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: co-trimoxazole
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral Co-trimoxazole (TMP-SMX) 160/800mg twice daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral co-trimoxazole 5mg TMP/kg maximum dose of 160mg TMP/ 800mg SMX twice daily.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Doxycycline
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline 100mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline (ages ≥ 8 years) 2mg/kg once daily maximum dose 100mg.

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Doxycycline
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline 100mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral doxycycline (ages ≥ 8 years) 2mg/kg once daily maximum dose 100mg.

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Moxifloxacin
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 400mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Moxifloxacin
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 400mg once daily. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral moxifloxacin 10-15mg/kg once daily, maximum dose 400mg

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Bedaquiline
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months).

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Bedaquiline
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral bedaquiline (18-64 years of age) 400mg once daily for the first two weeks followed by 400mg thrice weekly for 22 weeks (maximum duration of 6 months).

Intervention type: DRUG
Group type: ACTIVE_COMPARATOR
Intervention: Rifabutin
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin 5mg/kg once daily

Intervention type: DRUG
Group type: EXPERIMENTAL
Intervention: Rifabutin
Description: Adult: during consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin, bedaquiline or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin: 5mg/kg once daily, maximum 300-450mg. Children: During consolidation in combination with one to three oral antibiotics (co-trimoxazole, doxycycline, moxifloxacin or rifabutin) guided by participant susceptibility and tolerance. Oral rifabutin 5mg/kg once daily