Suri 2001.
| Methods | Prospective open‐label randomised controlled trial. Design: cross‐over with 3 treatment arms. 48 children were randomised, 8 to each of the 6 possible treatment orders. Duration: each arm lasted 12 weeks with a 2‐week washout period between treatments. Location: multicentre in UK (2 institutions). |
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| Participants | Total participants recruited: n = 48, but 1 withdrew without commencing treatment, so trial population is 47.
Age (mean (SD)): 12.6 (2.8) years, range (7.3 ‐ 17 years). Gender split: 19 (40%) males; 28 (60%) females. Weight (mean (SD)): 40·0 (12·6) kg, range (18·8 ‐ 77). Spirometry:
Lung microbiology (number of children with 3 positive cultures of the organism in the previous year):
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| Interventions | Pre‐treated with bronchodilators. All treatments were administered with a Sidestream nebuliser and Porta‐Neb compressor (Medic‐Aid, Bognor Regis, UK). Group 1: 5 mL HS 7% 2x daily immediately before the participant's regular physiotherapy session. Group 2: rhDNase 2.5 mg 1x daily at least 1 hour before physiotherapy. Group 3: 2.5 mg alternate daily at least 1 hour before physiotherapy. Routine medication and physiotherapy were continued throughout the trial. |
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| Outcomes | Primary outcome: % change in FEV1 from baseline. Secondary outcomes: FVC; number of pulmonary exacerbations (defined as a previously outlined protocol for respiratory‐tract infections); weight gain; exercise tolerance (3‐min step test and oxygen saturation monitored); QoL (quality of well‐being scale self‐administered form 1·04, filled out by the participant and guardian together); total health‐care cost (hospital and community‐health‐service perspective, so participants' costs excluded from analysis; resources included covered hospital admissions (inpatient, outpatient, and day case), radiological investigations, blood tests, drug use, and the use of community services (visits to general practitioners, district nurses, and physiotherapists)); adherence (count of unused bottles of HS and empty vials of rhDNase; each participant was also given a diary to record the treatment doses taken). |
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| Notes | Sample size calculation undertaken. Before starting the hypertonic‐saline treatment period, each participant received a test dose of HS in hospital so that he or she could be monitored for bronchoconstriction. |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Telephone randomisation to an independent trials coordinating unit, stratified by hospital and balanced after each group of 12 children. |
| Allocation concealment (selection bias) | Low risk | Telephone randomisation to an independent trials coordinating unit, |
| Blinding of participants and personnel (performance bias) All outcomes | High risk | No attempt to conceal taste, paper states masking impossible because HS can easily be distinguished from rhDNase by its salty taste and timing in relation to physiotherapy. |
| Blinding of outcome assessment (detection bias) All outcomes | Unclear risk | No statement on blinding of outcome assessors. |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | An ITT approach was used within this trial, 43 children are included in the comparison of daily and alternate‐day rhDNase, and 40 in the comparison of daily rhDNase and hypertonic saline. Details of withdrawals as follows:
In the additional report of airway inflammatory changes following treatment, only 28 of the 48 participants were able to perform induced sputum and be included. It is not evident that any attempts were made to adjust for missing data from those participants unable to do induced sputum. |
| Selective reporting (reporting bias) | Low risk | All outcomes stated in the methods were described in the results. |
| Other bias | Low risk | We judged a 2‐week washout period to be low risk. Sample size calculation undertaken. |