Phase 3 N=1,437 Randomized Quadruple-blind Treatment

TRIple in Asthma hiGh strenGth vErsus Ics/Laba hs and tiotRopium (TRIGGER)

Asthma

Bottom Line

View on ClinicalTrials.gov: NCT02676089 ↗

Enrolled (actual)

1,437

Serious AEs

5.3%

Results posted

May 2026

Primary outcome: Primary: 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26 — 0.229; 0.157; 0.274 Liter — p=0.003

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: CHF 5993 200/6/12.5 µg (Drug); CHF 1535 200/6 µg (Drug); CHF 1535 200/6 µg + Tiotropium Respimat 2.5 µg (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Chiesi Farmaceutici S.p.A.
Primary completion: May 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26	0.229; 0.157; 0.274	0.003 sig
PRIMARY 2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period	1.726; 1.963; 1.613	0.110
SECONDARY 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26	0.522; 0.417; 0.555	< 0.001 sig
SECONDARY 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment	10.102; 2.297; 10.286	0.001 sig
SECONDARY 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis	0.239; 0.310	0.008 sig
SECONDARY 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits	0.465; 0.407; 0.467; 0.533; 0.439; 0.559	0.003 sig
SECONDARY 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits	0.218; 0.149; 0.254; 0.241; 0.162; 0.250	0.001 sig
SECONDARY 8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52	328; 257; 174; 326; 241; 158	< 0.001 sig
SECONDARY 9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits	0.357; 0.309; 0.358; 0.443; 0.352; 0.472	0.006 sig
SECONDARY 10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits	-0.573; -0.513; -0.576; -0.699; -0.608; -0.704	0.089
SECONDARY 11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52	350; 319; 180; 356; 332; 168	0.088
SECONDARY 12_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment	9.805; 1.563; 8.055	0.002 sig
SECONDARY 12a_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment	8.965; -0.306; 14.249; 7.956; -1.686; 11.167	< 0.001 sig
SECONDARY 13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks	323; 364; 162	0.003 sig
SECONDARY 14_Number of Patients at Risk of Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	209; 257	0.011 sig
SECONDARY 15_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02.	1.515; 1.717	0.043 sig
SECONDARY 16_Number of Patients at Risk of MODERATE Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	588; 663	0.001 sig
SECONDARY 17_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 and CCD-055993AB2-02	1.788; 2.074	0.008 sig
SECONDARY 18_Number of Patients at Risk of Moderate OR Severe Asthma Exacerbation in the Pooled Analysis of the Two Pivotal Studies CCD-05993AB1-03 and CCD-05993AB2-02	660; 743	<0.001 sig
SECONDARY 19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period	1.430; 1.583; 1.366	0.250
SECONDARY 20_Number of Patients at Risk of a MODERATE Asthma Exacerbation	283; 320; 150	0.009 sig
SECONDARY 21_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods	-0.575; -0.550; -0.672; -0.638; -0.582; -0.686	0.640
SECONDARY 21a_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period	-0.409; -0.421; -0.543; -0.549; -0.559; -0.654	—
SECONDARY 22_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods	15.786; 14.570; 18.390; 17.566; 15.457; 19.740	0.425
SECONDARY 22a_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment	10.075; 11.380; 14.435; 14.196; 14.668; 17.854	—
SECONDARY 23_Change From Baseline in the Average Total Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods	-0.186; -0.175; -0.194; -0.208; -0.191; -0.207	0.564
SECONDARY 23a_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period	-0.116; -0.121; -0.140; -0.174; -0.171; -0.183	—
SECONDARY 24_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods	13.187; 10.358; 10.419; 16.569; 12.790; 12.725	0.055
SECONDARY 24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods	6.260; 5.316; 4.921; 11.267; 9.319; 9.663	—
SECONDARY 25_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods	12.469; 9.950; 10.356; 15.601; 12.088; 12.530	0.079
SECONDARY 25a_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period	6.014; 5.348; 5.078; 10.666; 9.138; 9.659	—

Summary

Evaluate the superiority of CHF 5993 200/6/12.5 µg pressurised metered dose inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate plus formoterol fumarate plus glycopyrronium bromide) versus CHF 1535 200/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate plus formoterol fumarate) in patients with uncontrolled asthma under medium doses of inhaled corticosteroid/long-acting β2-adrenergic receptor agonists (ICS/LABA), in patients with uncontrolled asthma who received medium doses of ICS/LABA. The treatments tested the improvement of the forced expiratory volume in the 1st second (FEV1) and the reduction of moderate and severe asthma exacerbations rate.

Eligibility Criteria

Inclusion Criteria

History of asthma ≥ 1 year and diagnosed before 40 years old
Uncontrolled asthma with double therapy only on high doses of Inhaled CorticoSteroid (ICS) in combination with Long-Acting Beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5
Pre-bronchodilator FEV1 = 10 packs year)
Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening

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Data sourced from ClinicalTrials.gov (NCT02676089). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.