Rifabutin for treating pulmonary tuberculosis

doi:10.1002/14651858.CD005159.pub2

Intervention Review

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Rifabutin for treating pulmonary tuberculosis

Geraint R Davies^1,*,
Stefania Cerri²,
Luca Richeldi²

Editorial Group: Cochrane Infectious Diseases Group

Published Online: 20 JAN 2010

Assessed as up-to-date: 5 JUL 2007

DOI: 10.1002/14651858.CD005159.pub2

Database Title

The Cochrane Library

Additional Information

How to Cite

Davies GR, Cerri S, Richeldi L. Rifabutin for treating pulmonary tuberculosis. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD005159. DOI: 10.1002/14651858.CD005159.pub2.

Author Information

¹
University of Liverpool, School of Clinical Sciences, Liverpool, Merseyside, UK
²
Policlinico di Modena, Universita di Modena e Reggio Emilia, Divisione di Pneumologia, Modena, Italy

^*Geraint R Davies, School of Clinical Sciences, University of Liverpool, Royal Liverpool University Hospital, Prescot Street, Liverpool, Merseyside, L7 8XP, UK. gerrydavies@doctors.org.uk.

Publication History

Publication Status: New search for studies and content updated (no change to conclusions)
Published Online: 20 JAN 2010

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Characteristics of included studies [ordered by study ID]

Gonzalez 1994

Methods	Randomized controlled trial Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: assessor only Inclusion of all randomized participants: 88% (154/175) for rifampicin, 94.8% (165/174) for rifabutin 150 mg, and 86.5% (148/171) for rifabutin 300 mg at 6 months; 70.9% (124/175) for rifampicin, 74.1% (129/174) for rifabutin 150 mg, and 73.7% (126/171) for rifabutin 300 mg

Participants	Number: 520 enrolled; number screened for entry not reported Inclusion criteria: tuberculosis patients with previously untreated disease; HIV serology negative; Mycobacterial culture positive on 2 separate occasions

Interventions	1. Rifabutin: 150 mg daily for 6 months 2. Rifabutin: 300 mg daily for 6 months 3. Rifampicin: 600 mg daily for 6 months Dose was not adjusted for weight Companion drugs: isoniazid (300 mg daily for 6 months); ethambutol (25 mg/kg daily for 2 months); and pyrazinamide (30 mg/kg daily for 2 months)

Outcomes	1. "Conversion of sputum bacterial cultures" at weeks 12 and 24 (composite primary outcome measure) 2. Relapse (over 24 months) 3. Time to sputum culture conversion

Notes	Location: multicentre study at 1 site in Argentina, 3 sites in Brazil, and 2 sites in Thailand Supervision: participants hospitalized for the first 2 months Follow up: sputum collected every 2 weeks during the initial phase of therapy, 89% follow up at 6 months, and 68% at 30 months; only 75% complete at the time of the available trial No power calculation was presented for any outcome measure

HKCS/BMRC 1992

Methods	Randomized controlled trial; matched pairs design Generation of allocation sequence: unclear Allocation concealment: central randomization Blinding: assessor only Inclusion of all randomized participants: 64.7% (11/17) in both arms

Participants	Number: 34 enrolled Inclusion criteria: tuberculosis patients failing first-line regimen and resistant to rifampicin, isoniazid, and streptomycin on susceptibility testing 34/88 screened were eligible: 18 were susceptible to 1 or more of above drugs; 13 culture negative; 13 died before entry; 6 declined to participate; and 4 were on ofloxacin

Interventions	1. Rifabutin: 450 mg if < 50 kg and 600 mg if > 50 kg daily for 12 months 2. Rifampicin 450 mg if < 50 kg and 600 mg if > 50 kg daily for 12 months Companion drugs: 1 to 3 other drugs given daily chosen from: pyrazinamide (1.5/2.0 g); ethambutol (25 mg/kg for 2 months followed by 15 mg/kg thereafter); ethionamide/prothionamide (500 mg); kanamycin (750 mg); capreomycin (750 mg); and para-aminosalicylic acid (10 g). Those who failed rifampicin could be switched to rifabutin, while those failing rifabutin could be switched to ofloxacin (800 mg daily)

Outcomes	1. Cure/failure at 12 months 2. "Temporary response" (ie culture conversion of limited duration) Not included in this review: 3. Smear and culture status at 2 months

Notes	Location: Hong Kong Supervision: included a mixture of inpatients and outpatients; duration of hospitalization not stated Follow up: sputum collected every 2 weeks for first 2 months then monthly; follow up was 65% at 12 months; 3 participants were culture negative at baseline, and the rest were excluded due to protocol violations Other: "temporary" responses were observed in 18/22 and did not differ between the regimens No power calculation was presented for any outcome measure

McGregor 1996

Methods	Randomized controlled trial Generation of allocation sequence: unclear Allocation concealment: unclear Blinding: assessor only Inclusion of all randomized participants: 75.6% (118/156) for rifampicin and 75.4% (107/142) for rifabutin at 6 months; and 32.1% (50/156) for rifampicin and 32.4% (46/142) for rifabutin at 30 months

Participants	Number enrolled: 298; number screened for entry was not reported Inclusion criteria: tuberculosis patients with previously untreated disease; Mycobacterial culture positive

Interventions	1. Rifabutin: 300 mg daily for 2 months then twice weekly for 4 months 2. Rifampicin: 600 mg daily for 2 months then twice weekly for 4 months Dose was not adjusted for weight Companion drugs: isoniazid (400 mg daily for 2 months then 600 mg twice weekly for 4 months); ethambutol (1200 mg daily for 2 months then 2400 mg twice weekly for 4 months); and pyrazinamide (2 g daily for 2 months)

Outcomes	1. "Bacteriological conversion at weeks 8, 12 and 24" (composite primary outcome measure) 2. Relapse (over 24 months) 3. Time to sputum culture conversion

Notes	Location: multicentre study at 8 sites in South Africa Supervision: ambulatory treatment from start was permitted, but most patients hospitalized were for 6 months Follow up: sputum collected every 2 weeks during initial phase of therapy; follow up was 75% at 6 months and 30% at 30 months HIV testing not carried out No power calculation was presented for any outcome measure

Rowinska 1992

Methods	Randomized controlled trial Generation of allocation sequence: unclear Allocation concealment: central randomization Blinding: assessor only Inclusion of all randomized participants: 100% (10/10 and 12/12 in the rifampicin and rifabutin arms respectively)

Participants	Number: 22 enrolled; number screened was not stated Inclusion criteria: tuberculosis patients with previously untreated disease; mycobacterial culture positive Exclusion criteria included alcoholism and psychological disturbance

Interventions	1. Rifabutin: 150 mg daily for 9 months 2. Rifampicin: 600 mg daily for 9 months Companion drugs: isoniazid (300 mg daily for 9 months) and ethambutol (20 mg/kg for 9 months)

Outcomes	1. Smear status at 2 months

Notes	Location: multicentre trial at 2 sites in Poland (Warsaw and Lodz) Supervision: participants hospitalized for duration of their treatment Follow up: unclear how often sputum samples were collected Other: there was also an arm for participants who had previously received treatment, but this was uncontrolled HIV testing not carried out No power calculation was presented for the outcome measure

Schwander 1995

Methods	Randomized controlled trial Generation of allocation sequence: consecutive drawing of randomly generated treatment orders Allocation concealment: numbered opaque envelopes Blinding: investigator and assessor (though for the former blinding was weak, see notes) Inclusion of all randomized participants: 100% (25/25) and 96% (24/25) in the rifampicin and rifabutin arms

Participants	Number enrolled: 50 Inclusion criteria: HIV-positive tuberculosis patients with previously untreated disease; sputum smear positive; suggestive chest x-ray Exclusion criteria included alcoholism

Interventions	1. Rifabutin: 150 mg if < 50 kg and 300 mg if > 50 kg daily for 6 months 2. Rifampicin: 450 mg if < 50 kg and 600 mg if > 50 kg daily for 6 months Companion drugs: isoniazid (300 mg daily for 6 months); pyrazinamide (1500 mg if < 50 kg and 2000 mg if > 50 kg daily for 2 months); and ethambutol (800 mg if < 50 kg and 1200 mg if > 50 kg daily for 2 months)

Outcomes	1. Smear status at 2 months 2. Time to sputum smear conversion

Notes	Location: Kampala, Uganda Supervision: ambulatory treatment in majority from an early stage, observed only once or twice a week Follow up: sputum samples collected every 2 weeks during the initial phase of therapy; cultures also done but only at the time of smear conversion Other: only 42/50 participants ultimately had culture confirmation of their positive smear; 7 participants who had no culture confirmation of Mycobacterium tuberculosis complex infection due to contamination were included in the analysis Note on allocation concealment: no placebos were used and the treatments differed in formulation so that both participants and carers could potentially determine allocation No power calculation was presented for any outcome measure

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion

Burman 2006	Nonrandomized design with no rifampicin control arm

Chan 1992	Monotherapy study in which no relevant outcome measures were reported

Sirgel 1993	Monotherapy study in which no relevant outcome measures were reported