Table 2.
Post-approval completed studies.
| Study | Design | Population | Intervention | Clinical outcomes | Comments |
|---|---|---|---|---|---|
| Wainwright et al27 (AIR-CF4) | R, DB, PCT | 157 CF patients with PA ⩾6 years FEV >75% |
28 days AZLI TID vs PBO | No change in CFQ-R ↑ FEV1 ↓ Sputum PA density |
Larger treatment effect FEV1 75%-90% Healthier patients Sample size |
| Assael et al28 (AZLI-TIS active comparator) | Open-label R, Parallel group |
268 CF patients with PA ⩾6 years FEV ⩽75% |
AZLI TID or TIS BID for 3 x28 day on/off cycles | ↑ FEV1 vs TIS ↓Hospitalizations ↓PE ↓Utilization of anti-PA antibiotics |
Study design Few pediatric patients Clinical application |
| Tullis et al29 (AZLI in Burkholderia) | R, DB, PCT | 100 CF patients ⩾6 years with chronic Burkholderia spp. infection | AZLI TID continuous for 24 weeks vs PBO then 24 week open-label extension | No change in lung function No change in sputum density |
Sample size Variable treatments resulting in confounders Heterogeneous population |
| Flume et al5 (AZLI CAT) | R, DB, PCT | 90 CF patients with PA ⩾6 years | Cyclic AZLI TID vs PBO with open-label TIS for 3 cycles | Non-significant ↓ in hospitalization and PE | Under enrolled with failure to meet power |
| Retsch-Bogart et al30 (combined pediatric experience) | Post hoc subset analysis of R, DB, PCT | 165 AIR-CF1, AIR-CF2, AIR-CF4, and AZLI-TIS active comparator Pediatric patients ⩾6 years to <18 years FEV1 25%-75% |
28 days AZLI vs PBO or 28 days of TIS then 28 days of AZLI BID or TID vs PBO |
↑ FEV1 similar to adults Slightly less respiratory adverse events than adults |
Subgroup analysis Sample size |
| Tiddens et al31 (ALPINE) | Single-arm, open-label | 105 CF patients with new PA 3 months to <18 years FEV1 ⩾80% |
28 days AZLI TID | 89.1% PA (–) at end of treatment 75.2% PA (–) 4 weeks post-treatment 58.2% PA (–) at all post-treatment time points |
Study design Culture sampling primarily by throat swab Primary outcome measure at the end of the study period High baseline negative culture rates |
| Accurso et al34 (PALS) | Single-arm, open-label | 61 pediatric CF patients ⩽12 years with PA | 28 days of AZLI TID for 3 cycles | No discontinuation for safety or tolerability reasons ↑ FEV1 ↑ CFQ-R |
Study design Not powered or designed to assess efficacy outcomes |
Abbreviations: AZLI, aztreonam lysine for inhalation; BID, twice daily; CAT, continuous alternating inhaled antibiotic therapy; CFQ-R, Cystic Fibrosis Questionnaire-Revised; DB, double-blind; FEV1, forced expiratory volume in one second; PA, Pseudomonas aeruginosa; PALS, Pediatric Aztreonam Lysine Safety; PBO, placebo; PCT, placebo-controlled trial; PE, pulmonary exacerbation; R: randomized; TID: three times daily; TIS, tobramycin inhaled solution.