Elkins 2006a.

Study characteristics
Methods	RCT. Design: parallel, double‐blind. Location: 16 adult or paediatric hospitals in Australia. Duration: 48 weeks. The trial was conducted between September 2000 and November 2003.
Participants	Total participants: n = 164, 93 males and 71 females, aged over 6 years. HS Group (n = 83) Age, mean (SD): 18.4 (9.3) years. Sex: 46% female. BMI, mean (SD): 19.9 (3.9). FEV1, mean (SD), range: 73 (21), 40 – 132. FVC, mean (SD), range: 85 (18), 45 ‐ 127. FEF25%-75%, mean (SD), range: 56 (34), 11 ‐ 155. Sputum: Pseudomonas aeruginosa: 79%; Staphylococcus aureus: 44%. Control Group (n = 81) Age, mean (SD): 18.7 (9.2) years. Sex: 42% female. BMI, mean (SD): 20.1 (3.6). FEV1, mean (SD), range: 76(21), 40 – 127. FVC, mean (SD), range: 88 (18), 44 ‐ 137. FEF25%-75%, mean (SD), range: 61 (35), 10 ‐ 151. Sputum: Pseudomonas aeruginosa: 78%; Staphylococcus aureus: 47%.
Interventions	Group 1: 4 mL HS 7% 2x daily. Group 2: 4 mL IS 0.09% 2x daily. Solutions were prepared by Pfizer, quinine sulphate (0.25 mg per mL) was added as a taste‐masking agent. Solutions were nebulized with a Pari LC PLUS jet nebulizer and a Pari Proneb Turbo compressor. A bronchodilator was administered before each inhalation of the trial solution. All other standard care was maintained throughout the trial.
Outcomes	Mean change in FEV1 and FVC at 4, 12, 36 and 48 weeks. QOL and pulmonary exacerbations.
Notes	Sample size calculation undertaken.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Concealed computer randomisation with minimisation algorithm to balance for age, FEV1 and long‐term treatment with rhDNase, use of physiotherapy and trial centre.
Allocation concealment (selection bias)	Low risk	Randomisation performed by a person not otherwise involved in the trial.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, participant blinding was achieved by masking the taste of the solutions with quinine sulphate. Participants and their clinicians, remained unaware of the treatment assignments throughout the trial.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The research assistants and the trial coordinator remained unaware of the treatment assignments throughout the trial.
Incomplete outcome data (attrition bias) All outcomes	Low risk	2 participants (1 from each group) withdrew voluntarily after randomisation and before first dose. 82 in HS group and 80 in control group included in ITT analysis. Withdrawals described as follows: HS Group: 15 in total withdrawn: 7 lost to follow‐up (2 owing to time constraints; 2 owing to insufficient perceived benefit from trial solution; 2 owing to adverse reaction to trial solution (cough); 1 provided no reason) and 8 stopped inhalations but continued visits (4 had adverse reaction to trial solution; 1 had cough and vomiting; 1 had pharyngitis and wheezing; 1 had voice changes; 1 had chest tightness; 2 could not tolerate taste of trial solution; 1 had insufficient benefit from trial solution; 1 lost interest). Control Group: 17 in total withdrawn: 10 lost to follow‐up (5 owing to time constraints; 3 owing to insufficient perceived benefit from trial solution; 1 failed to attend; 1 provided no reason) and 7 stopped inhalations but continued visits (3 owing to time constraints; 2 had adverse reaction to trial solution (tonsillitis in 1 and lethargy in 1); 1 had insufficient benefit from trial solution; 1 provided no reason.
Selective reporting (reporting bias)	Low risk	All outcomes stated in the methods were described in the results.
Other bias	Low risk	Sample size calculation undertaken, no other potential bias identified.