| Study | Intervention/Comparison | Population | Outcomes | Comments |
|---|---|---|---|---|
| Technology Appraisal | ||||
| NICE TA 276 (Tappenden 2013) | Comparison 1: Tobramycin DPI vs Tobramycin nebulised (EAGER trial) Comparison 2: Colistimethate sodium DPI vs tobramycin nebulised (COLO/DPI/02/06) Comparison 3: Colistimethate sodium DPI vs colistimethate sodium nebulised (Davies 2004, COLO/DPI/02/05) | People with cystic fibrosis ≥ 6 years and chronic P aeruginosa pulmonary colonisation. |
| All studies are RCTs, open label EAGER trial: Konstan 2011a Other outcomes included in the TA: Respiratory symptoms |
| Cochrane systematic reviews | ||||
| Remmington 2016 Cochrane SR | Comparison 1: Ciprofloxacin (500 mg) vs placebo (Sheldon 1993) | People with cystic fibrosis diagnosed by clinical features and all levels of severity of lung disease. |
| AMSTAR: 11/11 |
| Ryan 2011 Cochrane SR | Comparison 1: Aztreonam lysine vs placebo (McCoy 2008) Comparison 2: Colistin vs placebo (Hodson 2002, Jensen 1987) Comparison 3: Tobramycin vs placebo (Chuchalin 2007, Hodson 2002, Lenoir 2007, Murphy 2004, Ramsay 1993, Ramsay 1999) | People with cystic fibrosis diagnosed by clinical features and all levels of severity of lung disease. | Comparison 1: Aztreonam lysine vs placebo
Colistin vs placebo
Tobramycin vs placebo
| AMSTAR: 11/11 *reported in individual studies |
| Primary studies included in the TA or in the Cochrane SR | ||||
| Chuchalin 2007 (Hungary, Poland, Russia) RCT | Intervention Tobramycin (nebulised) 300 mg. 24 weeks: 4 weeks “on treatment”, followed by 4 weeks “off treatment” Comparison Placebo | N=247 people with cystic fibrosis and P aeruginosa ≥6 years Age range: 6 to 45 |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| COLO/DP I/02/05 (UK) Open label RCT, with cross-over | Intervention Colistin sodium DPI 125 mg, twice daily Comparison Colistin sodium solution 2 MU, twice daily Duration: 8 weeks | N=16 people with cystic fibrosis with chronic P aeruginosa infection ≥8 years Mean (SD) age: 20.3 (12.87) years |
| Included in NICE TA 276 Included in the review |
| COLO/DPI/02/06 (EU, Russia, Ukraine) Open label RCT | Intervention Colistin sodium DPI 125 mg; twice daily Comparison Tobramycin inhalation solution 300 mg/5 ml; twice daily Duration: 24 weeks | N=380 people with cystic fibrosis and P aeruginosa ≥6 years Mean (SD) age: 21.3 (9.72) vs 20.9 (9.30) years |
| Included in NICE TA 276 Included in the review |
| Hodson 2002 (UK) Open label RCT | Intervention Tobramycin (nebulised) 300 mg daily in 5ml twice daily Comparison Colistin (nebulised) 1MU in 3ml in saline twice daily Duration: 28 days | N=126 randomised (n=115 treated) people with cystic fibrosis Age range: 17 to 50 years |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| Jensen 1987 (Denmark) RCT | Intervention Colistin (nebulised) 1 million units, twice daily for 3 months Comparison Placebo (normal saline) | N=40 people with cystic fibrosis and chronic P aeruginosa infection ≥6 years Age range: 7 to 35 years |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| Konstan 2011a (EAGER trial) (15 countries, not specified) | Intervention Tobramycin inhalation powder 112 mg, 4-capsules, twice daily Comparison Tobramycin (nebulised) 300mg/5 ml, twice daily | N=121 people with cystic fibrosis ≥ 6 years and positive cultures of P aeruginosa within 6 months of screening Mean age (SD): 26 (11.4) vs 25 (10.2) |
| Included in NICE TA 276 Included in NMA and the review |
| Lenoir 2007 (France, Italy, Moldova, Ukraine) RCT | Intervention Tobramycin (nebulised) 300 mg twice daily for 4 weeks followed by a 4-week run-out phase Comparison Placebo | N=59 with cystic fibrosis and P aeruginosa infection ≥6 years Age range: 6 to 30 years |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| McCoy 2008 (Australia, Canada, New Zealand and USA) RCT | Intervention Aztreonam lysine 75 mg, for 4 weeks, 2 or 3-times daily Comparison Placebo (5 mg lactose in 1 ml 0.17% sodium chloride) | N=246 people with cystic fibrosis and documented P
aeruginosa infection Age range: 7 to 65 years |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| Murphy 2004 (USA) Open label RCT | Intervention Tobramycin (nebulised), 300 mg twice daily. Alternating 4-weekly cycles for 56 weeks Comparison No treatment | N=184 children and young people with cystic fibrosis with ≥2 cultures of P aeruginosa Age range: 6 to 15 years |
| Included in NMA only |
| Ramsey 1993 (USA) Crossover RCT | Intervention Tobramycin (nebulised) 600 mg, 3-times daily for 28 days, then cross-over for 2 28-days periods Comparison Placebo (0.5 normal saline) | N=71 people with cystic fibrosis and P aeruginosa sputum culture susceptible to tobramycin Mean age (SD): 17.7 years (1.25) |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| Ramsey 1999 (USA) RCT | Intervention Tobramycin (nebulised) 300mg twice daily for three 28-day on-off cycles Comparison Placebo (0.225 normal saline and 1.25 mg quinine) | N=520 people with cystic fibrosis infected with P aeruginosa Age: 18 years or older |
| Included in Cochrane SR Ryan 2011 Included in NMA and review |
| Sheldon 1993 (Canada) RCT | Intervention Ciprofloxacin 500 mg, for 10 days every 3 months for 4 courses Comparison Placebo | N=40 adults with cystic fibrosis and chronically infected with P aeruginosa (31 completed the trial) Age ≥ 18 years |
| Included in Cochrane SR Remington 2013 Included in review and review |
| Additional primary studies | ||||
| Assael 2013 (Europe and USA) Open label RCT | Intervention Aztreonam lysine 28-day course × 3 Comparison Tobramycin (inhaled) 28 days course, 3000 mg, 2-times/day | N=273 people with cystic fibrosis ≥6 years and PA-positive sputum culture within the previous 3 months Mean age (SD): 25.5 years (9.0) |
| Open label Included in NMA and review |
| Flume 2016 (USA) RCT | Intervention Aztreonam lysine plus tobramycin (nebulised) Comparison Tobramycin (nebulised) Enrolled subjects received TIS 300 mg twice daily (BID) during a 28-day run-in phase This was followed by randomisation to a 24-week comparative phase. Subjects received 3 cycles of 28-days of double-blind AZLI or placebo (1:1 randomisation) alternating with 28-days of open-label TIS. | N=88 people with cystic fibrosis ≥ 6 years and documented P aeruginosa infection Mean age (SD): 28.4 years (11.4) |
| Included in NMA and review |
| Galeva 2013 (EDIT trial) (Bulgaria, Estonia, Latvia, Lithuania, Romania, Russia, Egypt, and India) RCT | Intervention Tobramycin inhalation powder 112mg twice daily, as capsules administered via the T-326 dry powder inhaler Comparison Placebo | N=62 people with cystic fibrosis ≥6 years, and a positive sputum or throat culture for P.A within 6 months of screening and positive sputum culture for P.A at the screening visit Mean age (SD), years 12.9 (4.3) vs. 12.9 (4.7) |
| Included in NMA and review |
| Konstan 2011 (EVOLVE trial) (Bulgaria, Lithuania, Serbia, Argentina, Brazil, Chile, Mexico, USA) RCT | Intervention Tobramycin inhalation powder (112 mg), 28 day cycle followed by 2 28-day cycles open-label tobramycin inhalation powder Comparison Placebo, 28-day cycle followed by 2 28-day cycles open-label tobramycin inhalation powder Total duration 24 weeks | N=95 children, young people and adults with cystic fibrosis with a positive sputum or throat culture for P aeruginosa within 6 months of screening and a positive sputum culture for P aeruginosa at the screening visit Age: 6 to 21 years |
| Included in NMA and review |
| Retsch-Bogart 2009 (USA) RCT | Intervention Aztreonam lysine 75mg aztreonam, 52.5mg of lysine monohydrate Comparison Placebo (5mg lactulose) | N=164 people with cystic fibrosis and P
aeruginosa documented infection ≥ 6 years Mean age (range): 31.7 (11–74); 27.4 (7–54) |
| Included in NMA and review |
| Schuster 2013 (Europe - countries not specified) Open label RCT | Intervention Colistin DPI 1.6625 MU twice daily, 24 weeks Comparison Tobramycin inhalation solution 300 mg/5 ml twice-daily, three 28-day cycles | N=380 people with cystic fibrosis chronically colonised with P aeruginosa infection, ≥ 6 years Mean (SD) age: 21.1 (9.49) years |
| Open label Included in NMA and review |
| Trapnell 2012 (USA) RCT | Intervention Fosfomycin/Tobramycin (160/40 mg or 80/20 mg) Comparison Placebo | N=119 people with cystic fibrosis ≥ 18 years and confirmed P aeruginosa infection
|
| Included in NMA and review |
| Wainwright 2011 (Australia, USA) RCT | Intervention Aztreonam lysine 28 days + 14 days follow-up 75 mg/day, 3-times Comparison Placebo | N=157 people with cystic fibrosis ≥ 6 years Age range: 6 to 17 years |
| Included in NMA and review |
Cystic fibrosis: cystic fibrosis; CFQ-R: Cystic Fibrosis Questionnaire-Revised; DPI: dry powder for inhalation; FEV1: forced expiratory volume; ITT: intention to treat analysis: RCT: randomized controlled trial
From: 9, Pulmonary monitoring, assessment and management
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