Table 3

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 designPrimary outcomeSecondary outcomeResultsLimitationsAdverse eventsComments
Kerstjens [1]Two replicates, RCTsChange 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 bronchodilationInconsistency in the results between two trialsMost 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 exacerbationsMuch lower rate of severe exacerbations observed during the studies than reported in historical dataSimilar 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 24Annualised 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 exacerbationsLow 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.