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. 2020 May 1;2020(5):CD008649. doi: 10.1002/14651858.CD008649.pub4

Comparison 1. Mannitol versus control ‐ parallel studies of individuals with cystic fibrosis.

Outcome or subgroup title No. of studies No. of participants Statistical method Effect size
1.1 HRQoL ‐ respiratory (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.1.1 Up to 4 months 2 507 Mean Difference (IV, Fixed, 95% CI) ‐1.54 [‐4.69, 1.61]
1.1.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) ‐0.99 [‐4.50, 2.52]
1.2 HRQoL ‐ vitality (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.2.1 Up to 4 months 2 361 Mean Difference (IV, Fixed, 95% CI) 3.42 [‐0.21, 7.04]
1.2.2 Up to 6 months 2 325 Mean Difference (IV, Fixed, 95% CI) 4.84 [0.86, 8.82]
1.3 HRQoL ‐ physical (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.3.1 Up to 4 months 2 505 Mean Difference (IV, Fixed, 95% CI) ‐1.80 [‐4.72, 1.11]
1.3.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) 0.52 [‐2.75, 3.79]
1.4 HRQoL ‐ emotion (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.4.1 Up to 4 months 2 506 Mean Difference (IV, Fixed, 95% CI) ‐2.11 [‐4.56, 0.34]
1.4.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) ‐1.27 [‐3.74, 1.20]
1.5 HRQoL ‐ eating (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.5.1 Up to 4 months 2 505 Mean Difference (IV, Fixed, 95% CI) 0.81 [‐1.96, 3.58]
1.5.2 Up to 6 months 2 466 Mean Difference (IV, Fixed, 95% CI) 0.68 [‐2.29, 3.65]
1.6 HRQoL ‐ health (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.6.1 Up to 4 months 2 360 Mean Difference (IV, Fixed, 95% CI) ‐0.43 [‐4.18, 3.32]
1.6.2 Up to 6 months 2 325 Mean Difference (IV, Fixed, 95% CI) ‐0.21 [‐4.14, 3.72]
1.7 HRQoL ‐ social (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.7.1 Up to 4 months 2 504 Mean Difference (IV, Fixed, 95% CI) ‐1.20 [‐3.70, 1.30]
1.7.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) ‐1.47 [‐4.25, 1.32]
1.8 HRQoL ‐ body (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.8.1 Up to 4 months 2 500 Mean Difference (IV, Fixed, 95% CI) ‐3.10 [‐6.49, 0.29]
1.8.2 Up to 6 months 2 461 Mean Difference (IV, Fixed, 95% CI) ‐1.19 [‐4.51, 2.13]
1.9 HRQoL ‐ role (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.9.1 Up to 4 months 2 358 Mean Difference (IV, Fixed, 95% CI) 1.22 [‐2.21, 4.66]
1.9.2 Up to 6 months 2 324 Mean Difference (IV, Fixed, 95% CI) ‐1.43 [‐4.87, 2.00]
1.10 HRQoL ‐ weight (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.10.1 Up to 4 months 2 360 Mean Difference (IV, Fixed, 95% CI) ‐4.23 [‐10.28, 1.83]
1.10.2 Up to 6 months 2 325 Mean Difference (IV, Fixed, 95% CI) ‐3.27 [‐9.84, 3.31]
1.11 HRQoL ‐ digestion (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.11.1 Up to 4 months 2 505 Mean Difference (IV, Fixed, 95% CI) ‐1.49 [‐4.77, 1.78]
1.11.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) ‐1.07 [‐5.04, 2.90]
1.12 FEV1 ml (repeated measures, change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.12.1 up to 2 months 2 600 Mean Difference (IV, Fixed, 95% CI) 71.27 [36.00, 106.54]
1.12.2 Up to 4 months 2 600 Mean Difference (IV, Fixed, 95% CI) 64.54 [26.65, 102.42]
1.12.3 Up to 6 months 2 600 Mean Difference (IV, Fixed, 95% CI) 86.50 [45.15, 127.86]
1.13 FEV1 % predicted (repeated measures, change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.13.1 up to 2 months 2 600 Mean Difference (IV, Fixed, 95% CI) 2.98 [1.04, 4.92]
1.13.2 up to 4 months 2 600 Mean Difference (IV, Fixed, 95% CI) 3.26 [1.16, 5.35]
1.13.3 up to 6 months 2 600 Mean Difference (IV, Fixed, 95% CI) 3.89 [1.69, 6.08]
1.14 FVC mL (repeated measures, change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.14.1 Up to 2 months 2 600 Mean Difference (IV, Fixed, 95% CI) 87.81 [41.96, 133.66]
1.14.2 Up to 4 months 2 600 Mean Difference (IV, Fixed, 95% CI) 89.24 [40.55, 137.92]
1.14.3 up to 6 months 2 600 Mean Difference (IV, Fixed, 95% CI) 102.17 [48.40, 155.94]
1.15 FEF25-75 mL/s (repeated measures, change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.15.1 Up to 2 months 2 600 Mean Difference (IV, Fixed, 95% CI) 47.53 [‐16.42, 111.48]
1.15.2 Up to 4 months 2 600 Mean Difference (IV, Fixed, 95% CI) 31.30 [‐34.78, 97.37]
1.15.3 Up to 6 months 2 600 Mean Difference (IV, Fixed, 95% CI) 42.67 [‐28.07, 113.42]
1.16 Adverse events at up to 6 months(mild) 2   Risk Ratio (M‐H, Fixed, 99% CI) Subtotals only
1.16.1 Cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.82 [0.41, 8.07]
1.16.2 Haemoptysis 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.73 [0.26, 11.62]
1.16.3 Pharyngolaryngeal pain 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.04 [0.18, 5.97]
1.16.4 Throat irritation 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.30 [0.06, 176.31]
1.16.5 Productive cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.66 [0.15, 46.93]
1.16.6 Wheezing 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.66 [0.07, 6.59]
1.16.7 Asthma 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 0.22 [0.00, 14.79]
1.16.8 Bronchospasm 1 295 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.16.9 Condition aggravated 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.99 [0.10, 10.33]
1.16.10 Chest discomfort 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.40 [0.03, 5.66]
1.16.11 Chest pain 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 0.22 [0.00, 14.79]
1.16.12 Vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.99 [0.25, 63.83]
1.16.13 Post‐tussive vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.99 [0.10, 38.69]
1.16.14 Headache 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.43 [0.23, 25.79]
1.16.15 Decreased appetite 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 3.34 [0.06, 178.67]
1.16.16 Infections and infestations 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.37 [0.05, 2.78]
1.16.17 Musculoskeletal and connective tissue disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.66 [0.15, 46.93]
1.16.18 Skin and subcutaneous disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.33 [0.20, 55.34]
1.17 Adverse events at up to 6 months (moderate) 2   Risk Ratio (M‐H, Fixed, 99% CI) Subtotals only
1.17.1 Cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.15 [0.78, 12.77]
1.17.2 Haemoptysis 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 4.66 [0.50, 43.49]
1.17.3 Pharyngolaryngeal pain 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.43 [0.23, 25.79]
1.17.4 Throat irritation 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.01 [0.03, 133.11]
1.17.5 Productive cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.66 [0.02, 24.81]
1.17.6 Wheezing 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.44 [0.04, 4.57]
1.17.7 Asthma 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 1.33 [0.06, 30.80]
1.17.8 Bronchospasm 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 2.01 [0.03, 133.11]
1.17.9 Condition aggravated 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.82 [0.41, 8.03]
1.17.10 Chest discomfort 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.99 [0.25, 16.10]
1.17.11 Chest pain 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 0.22 [0.00, 14.79]
1.17.12 Vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.13 [0.00, 7.15]
1.17.13 Post‐tussive vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 4.62 [0.10, 224.14]
1.17.14 Headache 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.99 [0.18, 22.39]
1.17.15 Decreased appetite 1 295 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.17.16 Infections and infestations 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.04 [0.18, 5.95]
1.17.17 Musculoskeletal and connective tissue disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.10 [0.08, 15.63]
1.17.18 Skin and subcutaneous disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.22 [0.00, 14.59]
1.18 Adverse events at up to 6 months (severe) 2   Risk Ratio (M‐H, Fixed, 99% CI) Subtotals only
1.18.1 Cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.17 [0.24, 5.69]
1.18.2 Haemoptysis 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.55 [0.13, 18.99]
1.18.3 Pharyngolaryngeal pain 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.33 [0.20, 55.34]
1.18.4 Throat irritation 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.66 [0.05, 8.70]
1.18.5 Productive cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.6 Wheezing 2 600 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.7 Asthma 1 295 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.8 Bronchospasm 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 2.01 [0.03, 133.11]
1.18.9 Condition aggravated 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.67 [0.02, 25.14]
1.18.10 Chest discomfort 2 600 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.11 Chest pain 1 295 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.12 Vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.13 Post‐tussive vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.01 [0.03, 133.11]
1.18.14 Headache 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.98 [0.03, 131.35]
1.18.15 Decreased appetite 1 295 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.16 Infections and infestations 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.28 [0.02, 3.47]
1.18.17 Musculoskeletal and connective tissue disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) Not estimable
1.18.18 Skin and subcutaneous tissue disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.01 [0.03, 133.11]
1.19 Adverse events at up to 6 months (total) 2   Risk Ratio (M‐H, Fixed, 99% CI) Subtotals only
1.19.1 Cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.05 [0.90, 4.67]
1.19.2 Haemoptysis 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.88 [0.77, 10.85]
1.19.3 Pharyngolaryngeal pain 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.13 [0.54, 8.44]
1.19.4 Throat irritation 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.99 [0.18, 22.42]
1.19.5 Productive cough 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.99 [0.18, 22.30]
1.19.6 Wheezing 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.53 [0.10, 2.95]
1.19.7 Asthma 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 0.67 [0.05, 8.60]
1.19.8 Bronchospasm 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 3.34 [0.06, 178.67]
1.19.9 Condition aggravated 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.42 [0.44, 4.52]
1.19.10 Chest discomfort 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.16 [0.23, 5.74]
1.19.11 Chest pain 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 0.13 [0.00, 7.15]
1.19.12 Vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 1.46 [0.21, 10.28]
1.19.13 Post‐tussive vomiting 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 4.64 [0.30, 72.37]
1.19.14 Headache 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 3.31 [0.46, 24.06]
1.19.15 Decreased appetite 1 295 Risk Ratio (M‐H, Fixed, 99% CI) 3.34 [0.06, 178.67]
1.19.16 Infections and infestations 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 0.53 [0.16, 1.75]
1.19.17 Musculoskeletal and connective tissue disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.43 [0.23, 25.79]
1.19.18 Skin and subcutaneous tissues disorders 2 600 Risk Ratio (M‐H, Fixed, 99% CI) 2.44 [0.23, 25.82]
1.20 Participants with treatment‐related respiratory and thoracic adverse events leading to study discontinuation 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.20.1 Asthma 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 2.01 [0.08, 48.82]
1.20.2 Bronchospasm 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 2.01 [0.08, 48.82]
1.20.3 Cough 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 2.26 [0.85, 6.02]
1.20.4 Haemoptysis 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 3.33 [0.39, 28.25]
1.20.5 Hyperventilation 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 1.98 [0.08, 48.17]
1.20.6 Obstructive airways disorder 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 1.98 [0.08, 48.17]
1.20.7 Pharynolaryngeal pain 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 2.66 [0.30, 23.62]
1.20.8 Productive cough 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 1.98 [0.08, 48.17]
1.20.9 Throat irritation 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.66 [0.09, 4.70]
1.20.10 Wheezing 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.13 [0.01, 2.76]
1.21 Number of patients with protocol defined pulmonary exacerbations 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.21.1 Up to 6 months 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.71 [0.51, 0.98]
1.22 Time to first protocol defined pulmonary exacerbation (PDPE) 2 600 Hazard Ratio (IV, Fixed, 95% CI) 0.70 [0.48, 1.02]
1.23 Number of patients needing additional antibiotics 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.23.1 Intravenous 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.70, 0.95]
1.24 Number of participants requiring hospitalisation 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.24.1 With pulmonary exacerbation, up to 6 months 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.83 [0.60, 1.15]
1.24.2 With PDPE, up to 6 months 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.78 [0.53, 1.15]
1.25 Duration of hospitalisation 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.25.1 Duration of hospitalisation with pulmonary exacerbation, up to 6 months (days) 2 600 Mean Difference (IV, Fixed, 95% CI) ‐1.04 [‐2.58, 0.50]
1.25.2 Duration of hospitalisation with PDPE, up to 6 months (days) 2 600 Mean Difference (IV, Fixed, 95% CI) ‐0.64 [‐1.87, 0.60]
1.26 Sputum weight (g) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.26.1 at 14 weeks 2 460 Mean Difference (IV, Fixed, 95% CI) 1.02 [‐0.10, 2.14]
1.27 Sputum weight (g) (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.27.1 Up to 4 months 2 439 Mean Difference (IV, Fixed, 95% CI) ‐0.95 [‐2.05, 0.15]
1.28 Microbiology: pathogens present at end of study 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.28.1 Pseudomonas aeruginosa (mucoid) 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 0.90 [0.69, 1.17]
1.28.2 Pseudomonas aeruginosa (non‐mucoid) 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 0.73 [0.53, 1.03]
1.28.3 Pseudomonas aeruginosa (not specified) 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 3.80 [0.45, 31.97]
1.28.4 Pseudomonas spp (other) 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 1.15 [0.42, 3.17]
1.28.5 Staphylococcus aureus 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 1.02 [0.81, 1.28]
1.28.6 Methicillin‐resistant Staphylococcus aureus 1 263 Risk Ratio (M‐H, Fixed, 95% CI) 1.18 [0.58, 2.39]
1.28.7 Burkholderia cepacia (cenocepacia) 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 0.69 [0.32, 1.48]
1.28.8 Aspergillus spp 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 0.82 [0.51, 1.30]
1.28.9 Candida spp 2 461 Risk Ratio (M‐H, Fixed, 95% CI) 0.81 [0.49, 1.33]
1.29 Burden of treatment (change from baseline) 2   Mean Difference (IV, Fixed, 95% CI) Subtotals only
1.29.1 Up to 4 months 2 505 Mean Difference (IV, Fixed, 95% CI) ‐4.60 [‐7.90, ‐1.30]
1.29.2 Up to 6 months 2 465 Mean Difference (IV, Fixed, 95% CI) ‐2.12 [‐5.70, 1.46]
1.30 Adherence ≥ 60% 2   Risk Ratio (M‐H, Fixed, 95% CI) Subtotals only
1.30.1 Up to 6 months 2 600 Risk Ratio (M‐H, Fixed, 95% CI) 0.89 [0.82, 0.97]