Stephens 1983.
| Methods | Randomised controlled trial. Parallel design. Single centre in Canada. Duration: 14 days. |
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| Participants | 28 people with CF (no information on how CF diagnosed) admitted to hospital for treatment of pulmonary exacerbation. IV + inhaled group: n = 16; IV alone group: n = 12. Age: IV + inhaled: mean (SD) 15.3 (3.5) years; IV: mean (SD) 15.1 (4.7) years. Age range for both groups 7 ‐ 22 years. Gender: IV + inhaled: 9 males, 7 females; IV: 9 males, 3 females. Clinical status: admitted to hospital for treatment of exacerbation (no definition given). Groups comparable in age and details listed below. Mean (SD) Schwachman score: IV + inhaled: 53.4 (9.5); IV: 55.4 (9.0). Mean (SD) FEV1 % predicted: IV + inhaled: 64.3 (11.8); IV: 72.2 (10.9). Mean (SD) FEF25‐75 % predicted: IV + inhaled: 30.6 (26.5); IV: 36.6 (21.0). Mean (SD) log10 sputum colony count of P aeruginosa: IV + inhaled: 6.9 (1.6); IV: (7.4 (1.2). |
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| Interventions |
IV + inhaled: IV (tobramycin 10 mg/kg/day in 3 divided doses plus ticarcillin 300 mg/kg/day in 4 divided doses, each dose infused over 30 minutes) plus 80 mg aerosolized tobramycin mixed with 1 ml salbutamol and 2 ml buffering nebulising solution 3x daily via a Bennet twin jet nebulizer. IV alone: tobramycin 10 mg/kg/day in 3 divided doses plus ticarcillin 300 mg/kg/day in 4 divided doses, each dose infused over 30 minutes. |
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| Outcomes | FEV1, FVC, FEF25‐75, need for hospital admission, weight, adverse effects, emergence of resistant organisms, serum concentrations, sleeping pulse and respiratory rates, temperature, Schwachman score, sputum culture, antimicrobial sensitivities. Data reported at start of trial and discharge from hospital (25 participants discharged after 14 days, 2 from treatment and 1 from control group discharged at 21 to 26 days). Serum concentrations for adjustment of IV tobramycin measured on days 1, 5 and 12 ‐ day 5 not reported in paper. |
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| Notes | All P aeruginosa strains sensitive to ≤8 µg/ml tobramycin and ≤100 µg/ml ticarcillin. For FEV1 and weight, paper reports means, but no SDs, so data can not be entered into RevMan. Paper also reports that "Eradication of Pa transient and all children re‐colonized within 1 to 2 months after discharge." Sample size calculation not reported. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | Paper states "allocated randomly to either the control or treatment groups" but process not described. |
| Allocation concealment (selection bias) | Unclear risk | Not discussed. |
| Blinding (performance bias and detection bias) Participant | High risk | Not possible, IV + inhaled versus IV alone. |
| Blinding (performance bias and detection bias) Caregiver or clinician | High risk | Not possible, IV + inhaled versus IV alone. |
| Blinding (performance bias and detection bias) Outcome assessor | Low risk | For lung function tests paper states "technician performing the tests was not aware of the treatment", but no details given for other outcome measures. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Appear to be no withdrawals. |
| Selective reporting (reporting bias) | High risk | Data for FVC not reported. Furthermore, paper states that "Serum concentrations were obtained prior to and 30 minutes after completion of the 30‐min infusion. Serum concentrations of tobramycin and ticarcillin were measured on day 1, 5 and 12. Sleeping pulse & respiratory rates recorded daily and body temp (oral) 4 times a day. Schwachman score, quantitative sputum culture & antimicrobial sensitivities pulmonary function tests were performed at entry and at end of 2 weeks of treatment. Sputum obtained prior to 1st morning dose of inhaled tobramycin." Table 2 in the paper reports these clinical status data for start and at end of treatment, but no data are given for day 5 ‐ unclear if this is selectively reported or not. |
| Other bias | Low risk | No other bias identified. |
BMI: body mass index CF: cystic fibrosis FEF25‐75: mid‐expiratory flow FEV1: forced expiratory volume at one second FRC: functional residual capacity FVC: forced vital capacity IV: intravenous P aeruginosa: Pseudomonas aeruginosa PEG: percutaneous endoscopic gastrostomy QoL: quality of life RV: residual volume SD: standard deviation VC: vital capacity