Chuchalin 2007.
| Methods | Double‐blind, placebo‐controlled RCT. Allocation used was 2:1 (tobramycin: placebo). Parallel design. Duration: 24 weeks (4 weeks 'on treatment' followed by 4 weeks 'off treatment'). Multicentre: 21 sites across Hungary, Poland and Russia. |
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| Participants | Diagnosis of CF and P aeruginosa. 247 randomised; 245 included in ITT population. Gender split n (% males): 135 (55 %) Age range: 6 to 31 years (tobramycin group), 6 to 45 (placebo group). Excluded if received antibiotic therapy in 4 weeks running up to enrolment. Baseline FEV1 % predicted (mean (SD)) tobramycin group 60.7 (14.8); placebo group 63.6 (15.0) |
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| Interventions |
Intervention 1: tobramycin 300 mg (Bramitob®). Intervention 2: placebo (saline solution with quinine hydrochloride solution). Administered for 24 weeks (4 weeks 'on treatment' followed by 4 weeks 'off treatment') using a Pari LC Plus jet nebuliser and Pari Turbo Boy air compressor. |
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| Outcomes | FEV1, FVC, FEF25‐75, sputum (P aeruginosa density, tobramycin susceptibility), other pathogens, pulmonary exacerbations, use of parenteral anti‐pseudomonal antibiotics, number of hospitalisations, loss of school/work days, audiometric test, renal function, adverse events. | |
| Notes | Supported by Chiesi Famaceutici SpA (Italy), MDS Pharma Services (France). | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Randomised. Method not stated, ratio tobramycin to placebo 2:1. |
| Allocation concealment (selection bias) | Unclear risk | Not stated. Multicentre. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Double‐blind, quinine hydrochloride added to placebo to mask taste. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No specific details given about outcome assessors, but described as double‐blind. |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | 247 randomised, 245 ITT analysis, 215 PP analysis. 232 completed, 6.1% dropout rate (tobramycin group 7 dropouts (4.3%), placebo group 8 dropouts (9.3%)). Reasons given. |
| Selective reporting (reporting bias) | Unclear risk | Not clear if results for microbiology are ITT or PP. |
| Other bias | Unclear risk | Pharmaceutical industry support. |