Summary of the randomised controlled trials (RCTs) analysing triple therapy with LAMA, LABA and ICS in a single inhaler in asthma
| First author [ref.] | Study design | Primary outcome | Secondary outcome | Results | Limitations | Adverse events | Comments |
| Kerstjens [1] | Two replicates, RCTs | Change from baseline FEV1 at week 24 Time to first severe asthma exacerbation | Peak and trough FEV1 and FVC at each treatment visit Time to the first asthma exacerbation | Addition of tiotropium significantly increased the time to the first severe exacerbation and provided modest sustained bronchodilation | Inconsistency in the results between two trials | Most events were mild Dry mouth (<2% all patients, but was reported more frequently in the tiotropium group than in the placebo group) | |
| Virchow [2] | Two parallel-group, double-blind, randomised, active-controlled, phase 3 trials (TRIMARAN and TRIGGER) | Change from pre-dose FEV1 at week 26 Annualised rate of moderate/severe exacerbations over 52 weeks | Change from baseline in peak FEV1 at week 26 Average morning PEF over the first 26 weeks in each study Rate of severe exacerbations | Addition of a LAMA (glycopyrronium) improves lung function and reduces exacerbations | Much lower rate of severe exacerbations observed during the studies than reported in historical data | Similar across treatment groups Most events were mild | |
| Lee [3] | Double-blind, randomised, parallel-group, phase 3A study (CAPTAIN) | Change from the baseline FEV1 at week 24 | Annualised rate of moderate and/or severe asthma exacerbations Change from baseline in SGRQ Change from baseline in ACQ-7 total score | Adding UMEC improved lung function but did not lead to a significant reduction in moderate and/or severe exacerbations | Low rate of exacerbations compared to other studies Most patients received a lower ICS dose compared to their usual baseline dose during run-in/stabilisation period | Similar across treatment groups (dry mouth/drying of the airway secretions) Most events were mild | Post-hoc and prespecified subgroup analyses by biomarkers of type 2 inflammation |
FVC: forced vital capacity; PEF: peak expiratory flow; SGRQ: St George's Respiratory Questionnaire; ACQ: Asthma Control Questionnaire.