AzTrials
AzTrials

AsthmaPhase 3TRIMARANNCT02676076

TRIple in asthMA With uncontRolled pAtient on Medium streNgth of ICS + LABA

A Phase 3 study testing CHF 5993 100/6/12.5 and CHF 1535 100/6 µg in people with Asthma, run by Chiesi Farmaceutici S.p.A. at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Evaluate the superiority of CHF 5993 100/6/12.5 µg Pressurised Metered Dose Inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate (FF) plus glycopyrronium bromide [GB]) versus CHF 1535 100/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate (BDP) plus… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Asthma
What is being tested?
CHF 5993 100/6/12.5 and CHF 1535 100/6 µg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,155 participants
Where
1 siteGermany
Study dates
17 Feb 2016to 17 May 2018
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • History of asthma ≥ 1 year and diagnosed before 40 years old
  • Uncontrolled asthma with double therapy only on medium doses of Inhaled CorticoSteroid (ICS) in combination with Long-acting beta2 Agonist (LABA) with ACQ-7 (Asthma Control Questionnaire) ≥1.5
  • Pre-bronchodilator FEV1 <80% of the predicted normal value
  • Positive reversibility test
  • At least 1 documented asthma exacerbation in the previous year

Who cannot join

  • Pregnant or lactating women
  • Diagnosis of Chronic Obstructive Pulmonary Disease (COPD)
  • Patients with any asthma exacerbation or respiratory tract infection in the 4 weeks prior screening
  • Current or ex-smokers (>= 10 packs year)
  • Any change in dose, schedule or formulation of ICS + LABA combination in the 4 weeks prior screening

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Chiesi Clinical Trial Site 276814

    Rostock

Other trials in Germany

About this study

Official title: A 52 WEEK, RANDOMIZED, DOUBLE BLIND, MULTINATIONAL, MULTICENTRE, ACTIVE CONTROLLED, 2-ARM PARALLEL GROUP TRIAL COMPARING CHF 5993 100/6/12.5 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE PLUS GLYCOPYRRONIUM BROMIDE) TO CHF 1535 100/6 µg pMDI (FIXED COMBINATION OF EXTRAFINE BECLOMETHASONE DIPROPIONATE PLUS FORMOTEROL FUMARATE) IN PATIENTS WITH ASTHMA UNCONTROLLED ON MEDIUM DOSES OF INHALED CORTICOSTEROIDS IN COMBINATION WITH LONG ACTING ß2 AGONISTS

Evaluate the superiority of CHF 5993 100/6/12.5 µg Pressurised Metered Dose Inhaler (pMDI) (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate (FF) plus glycopyrronium bromide [GB]) versus CHF 1535 100/6 µg pMDI (fixed combination of extrafine beclometasone dipropionate (BDP) plus formoterol fumarate [FF]), with regard to lung functions parameters and rate of exacerbations as well as safety and health economics outcomes, in adult patients with uncontrolled asthma on medium doses of inhaled corticosteroids in combination with long acting ß2 agonists (LABA).

Read the detailed description

This study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice (GCP) guidelines, and following all other requirements of local laws.

From screening to the end of treatment, vital signs were recorded pre-dose at screening and pre- and postdose at all visits during the treatment period; physical examination was performed at all visits; concomitant medications and adverse events (AEs) were recorded, and asthma exacerbations were assessed at all visits; lung function tests were performed (pre-dose for forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) from screening to end of treatment visits, pre-dose for inspiratory capacity and vital capacity and postdose serial spirometry at all visits during the treatment period).

Patients completed the electronic diary from home twice daily from the time of screening until the end of treatment, to record asthma symptoms, treatment compliance, and use of rescue medication. Patients used the electronic peak flowmeter to record peak expiratory flow twice daily from home from the time of screening until the end of treatment.

Asthma Control Questionnaire© (ACQ)-7 was completed at screening and all visits during the treatment period. The EuroQuality of Life-5-Dimensional-3-Level questionnaire, and health economic and outcome assessments were competed at all visits during the treatment period.

Rescue medication (salbutamol 100 μg per inhalation) was permitted throughout the treatment period when absolutely needed; the maximum allowed dose was 8 inhalations/day (800 μg).

An independent Data Safety Monitoring Board was established to provide impartial safety evaluation and assurance for patients.

Conditions
Asthma
Being tested
CHF 5993 100/6/12.5, CHF 1535 100/6 µg
Keywords
asthma, anticholinergics, triple combination
Medical subject headings
Asthma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CHF 5993 100/6/12.5Drug

    BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg; GB=Glycopyrronium Bromide 12.5µg.

  • CHF 1535 100/6 µgDrug

    BDP=Beclometasone Dipropionate 100µg; FF=Formoterol Fumarate 6µg.

Study groups in NCT02676076
Study groupRoleWhat they receive
CHF 5993 100/6/12.5 µgExperimentalCHF 5993 100/6/12.5 CHF 5993 100/6/12.5 µg: 2 inhalations bid Total daily dose: 400/24/50 µg BDP/FF/GB BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate GB=Glycopyrronium Bromide
Receives: Drug: CHF 5993 100/6/12.5
CHF 1535 100/6 µgActive comparatorCHF 1535 100/6 µg CHF 1535 100/6 µg: 2 inhalations bid Total daily dose: 400/24 µg BDP/FF BDP=Beclometasone Dipropionate bid=Twice daily FF=Formoterol Fumarate
Receives: Drug: CHF 1535 100/6 µg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26

    Change from baseline in pre-dose FEV1 was analysed at Week 26 of treatment.

    FEV1=Forced expiratory volume in the first second

    Measured: Week 0 (pre-treatment, baseline) to Week 26.

  2. 2_Moderate and Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period

    Asthma exacerbation (events): Moderate AND Severe.

    Severe: asthma worsening requiring initiation of treatment with systemic corticosteroids for at least 3 days (courses of corticosteroids separated by ≥1 week treated as separate severe exacerbations).

    Moderate: ≥1 of the following criteria fulfilled and leading to a change in treatment (sustained increase of ≥1 puff of short acting beta 2-agonist [SABA] for 2 consecutive days) as shown below:

    • Nocturnal awakening(s) due to asthma requiring SABA for 2 consecutive nights/increase of ≥0.75 from baseline in daily symptom score on 2 consecutive days; increase from baseline in occasions of SABA use on 2 consecutive days (minimum increase 4 puffs/day);
    • ≥20% decrease in peak expiratory flow from baseline on at least 2 consecutive mornings/evenings or ≥20% decrease in FEV1 from baseline;
    • Visit to the ER/trial site for asthma treatment not requiring systemic corticosteroid.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

Secondary outcomes (29)

  1. 3_Change From Baseline in Peak(0-3h) FEV1 at Week 26

    Peak FEV1 was analysed within 3 hours post-dose.

    FEV1=Peak of forced expiratory volume in the first second

    Measured: Week 0 (pre-treatment, baseline) and Week 26.

  2. 4_Change From Baseline in Morning Peak Expiratory Flow (PEF) Over the 26-Week Treatment

    Change from baseline in the average morning PEF over the 26-Week treatment.

    PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

    Measured: Week 0 (pre-treatment, baseline) to Week 26.

  3. 5_Severe Asthma Exacerbation Rate Over the 52-Week Treatment Period - Pooled Analysis

    Severe Asthma Exacerbation Rate over the 52-Week Treatment Period in a pre-specified pooled analysis of 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER).

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: The entire treatment period; up to Week 52.

  4. 6_Change From Baseline in Peak FEV1 (0-3h) at All Clinical Visits

    Change from baseline in peak FEV1 (within 3 h post-dosing) at all clinical visits.

    Baseline for pre-dose FEV1 was calculated as average of the FEV1 measurements (L) from the visit 2 (V2) Pre45min \& V2 Pre15min. If one of the two pre-dose values was missing, the baseline was equal to the available pre-dose value.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  5. 7_Change From Baseline in Pre-Dose FEV1 at All Clinical Visits

    Results show the change from baseline in pre-dose FEV1 at all clinical visits.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  6. 8_FEV1 Response (FEV1 ≥ 100 mL) at Week 26 and Week 52

    Results show the percentage of patients classified as FEV1 responders at both Week 26 and Week 52. FEV1 response: Change from baseline in pre-dose morning FEV1 ≥ 100 mL.

    Measured: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

  7. 9_Change From Baseline in FEV1 Area Under the Curve (AUC) (0-3h) Normalised by Time at All Clinical Visits

    Baseline definition: mean of two pre-dose FEV1 measurements at visit 2 (V2).

    Results show the change from baseline in FEV1 area under the curve [AUC] (0-3h) at all subsequent visits (i.e. change from baseline of the AUC of the serial post-dose spirometry assessments till 3h post-dose).

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  8. 10_Change From Baseline in the Asthma Control Questionnaire-7 (ACQ-7) Score at All Clinical Visits

    ACQ-7 Questionnaire.

    Asthma Control Questionnaire-7 (ACQ-7) allows assessment of asthma control in individual patients.

    The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on lung function (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control (no impairment) and 6 indicating poor control (maximum impairment). The questions are equally weighted and the total score is the mean of the seven items. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer.

    Baseline for ACQ-7 was the total score recorded at Visit 2 (Week 0) of the study. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. A negative change from baseline indicates improvement in lung function.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  9. 11_Asthma Control Questionnaire©-7 Response at Week 26 and Week 52

    Asthma Control Questionnaire (ACQ) and Asthma Control Questionnaire-7 (QAC-7) are defined in the description of Outcome measure 10 above.

    An ACQ-7 response was defined as change from baseline (Week 0, pre-dose) in ACQ-7 score ≤ -0.5; non-response was defined as change from baseline in ACQ-7 score >-0.5 or missing data.

    Results represent the responders (i.e. change from baseline in ACQ-7 Score ≤ -0.5) at Week 26 and Week 52.

    Measured: Week 0 (pre-treatment, baseline) to Week 26 and Week 52

  10. 12a_Change From Baseline in Average Morning PEF (L/Min) Over 52 Weeks of Treatment

    Change from baseline in average MORNING PEF (L/min) over 52 weeks of treatment.

    PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  11. 12b_Change From Baseline in Average Evening PEF (L/Min) Over 26 and 52 Weeks of Treatment

    Change from baseline in average EVENING PEF (L/min) over 26 and 52 weeks of treatment.

    PEF=Peak expiratory flow; is the volume of air forcefully expelled from the lungs in one quick exhalation.

    Measured: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

  12. 13_Number of Patients at Risk of Moderate or Severe Asthma Exacerbation Over 52 Weeks

    Data were analysed for the number of patients at risk of a moderate or severe asthma exacerbation.

    Results show the number of patients who had moderate or severe asthma exacerbation over the 52 weeks treatment period.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  13. 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

    Data were analysed for the number of patients at risk of a severe asthma exacerbation in the pooled analysis of the two pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER).

    Results show the number of patients who had a severe asthma exacerbation over the 52 weeks treatment period.

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: Week 0 (Baseline) to 52 weeks for both studies in the pooled analysis.

  14. 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.

    Moderate asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-055993AB2-02 (TRIGGER).

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  15. 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

    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.

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  16. 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

    Moderate and severe asthma exacerbation rate over the 52-Week treatment period in the pooled analysis of the 2 pivotal studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER).

    Results show the number of participants with moderate and severe asthma exacerbation.

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  17. 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

    Time to first moderate or severe asthma exacerbation in the Pooled Analysis of the 2 Pivotal Studies CCD-05993AB1-03 (TRIMARAN) and CCD-05993AB2-02 (TRIGGER).

    Results show the number of participants with moderate or severe asthma exacerbation.

    The pooled analysis of pivotal studies TRIMARAN and TRIGGER was a pre-specified secondary outcome measure for this study. Both studies have identical design, duration, endpoints, data collection, and statistical methodology for analyses. TRIMARAN and TRIGGER enrolled patients under medium dose and high dose ICS/LABA, respectively. Both studies were designed to assess the effect of the LAMA on ICS/LABA and showed homogeneity in terms of baseline characteristics, thus confirming the appropriateness of the pooling.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  18. 19_Moderate Asthma Exacerbation Rate Over the 52-Week Treatment Period

    Moderate asthma exacerbation rate over the 52-Week treatment period.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  19. 20_Number of Patients at Risk of a MODERATE Asthma Exacerbation

    Data were analysed for the number of patients at risk of a MODERATE asthma exacerbation.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  20. 21a_Change From Baseline in the Average Use of Rescue Medication Over the 26- and 52-Week Treatment Periods

    Change from baseline in the average use of rescue medication over the 26- and 52-Week treatment periods.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Measured: Week 0 (pre-treatment, baseline) to Week 26 and Week 52.

  21. 21b_Change From Baseline in the Average Use of Rescue Medication in Each Inter-Visit Period

    Results show the change from baseline in the average use (puffs/day) of rescue medication in each inter-visit period.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  22. 22a_Change From Baseline in the Percentage of Rescue Medication-Free Days Over the 26- and 52-Week Treatment Periods

    Change from baseline in the percentage of rescue medication-free days in each inter-visit period over the 26- and 52-Week treatment periods.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  23. 22b_Change From Baseline in the Percentage of Rescue Medication-Free Days in Each Inter-Visit Period Over the Treatment

    Results show the change from baseline in the percentage of rescue medication-free days in each inter-visit period over the entire treatment.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  24. 23a_Change From Baseline in the Average Daily Asthma Symptom Scores Over the 26- and 52-Week Treatment Periods

    Data was collected through an electronic daily diary from screening to the end of the study.

    Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Weeks of treatment.

    A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day.

    Symptoms considered: cough, wheeze, chest tightness, breathlessness.

    • Morning (night-time asthma symptom score):
    • 0 No symptoms;
    • 1 Mild = Symptoms not causing awakening;
    • 2 Moderate = Discomfort enough to cause awakenings;
    • 3 Severe = Causing awakenings for most of the night/did not sleep at all.
    • Evening (daytime asthma symptom score):
    • 0 No symptoms;
    • 1 Mild = Aware of symptoms, which could be easily tolerated;
    • 2 Moderate = Discomfort enough to cause interference with daily activity;
    • 3 Severe = Incapacitating

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  25. 23b_Change From Baseline in the Average Daily Asthma Symptom Scores in Each Inter-Visit Period

    Results show the change from baseline in the average daily asthma symptom scores in each inter-visit period over the entire treatment. Data was collected daily through an electronic diary from screening to the end of the study.

    A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day.

    Symptoms considered: cough, wheeze, chest tightness, breathlessness.

    • Morning (night-time asthma symptom score):
    • 0 No symptoms;
    • 1 Mild = Symptoms not causing awakening;
    • 2 Moderate = Discomfort enough to cause awakenings;
    • 3 Severe = Causing awakenings for most of the night/did not sleep at all.
    • Evening (daytime asthma symptom score):
    • 0 No symptoms;
    • 1 Mild = Aware of symptoms, which could be easily tolerated;
    • 2 Moderate = Discomfort enough to cause interference with daily activity;
    • 3 Severe = Incapacitating

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  26. 24a_Change From Baseline in the Percentage of Asthma Symptom-Free Days Over the 26- and 52-Week Treatment Periods

    Change from baseline in the percentage of asthma symptom-free days over the 26- and 52-Week treatment periods.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Results show the change from baseline in the average daily asthma symptom scores over the 26- and 52-Week treatment periods. A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day.

    Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness.

    An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  27. 24b_Change From Baseline in the Percentage of Asthma Symptom-Free Days in Each Inter-Visit Periods

    Results show the change from baseline in the percentage of asthma symptom-free days in each inter-visit periods over the entire treatment.

    Data was collected through an electronic daily diary from screening to end of the study.

    A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day.

    Symptoms considered by the questionnaire: cough, wheeze, chest tightness, breathlessness.

    An asthma symptom-free day is a day with total daily asthma symptom score = 0. For a description of the score see outcome measure number 23.

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  28. 25a_Change From Baseline in the Percentage of Asthma Control Days Over the 26- and 52-Week Treatment Periods

    Results show the change from baseline in the percentage of asthma control days over the 26- and 52-Week treatment periods.

    Data was collected through an electronic daily diary from screening to the end of the study.

    Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness):

    Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all).

    Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity).

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

  29. 25b_Change From Baseline in the Percentage of Asthma Control Days in Each Inter-Visit Period

    Results show the change from baseline in the percentage of asthma control days in each inter-visit period.

    A day represents data recorded in the evening session of that day plus the data recorded in the morning session of the next day.

    Data was collected through an electronic daily diary from screening to the end of the study

    Scoring of asthma symptoms (overall symptoms, cough, wheeze, chest tightness and breathlessness):

    Morning (night-time asthma symptoms): 0 (no symptoms), 1 (mild - symptoms not causing awakening), 2 (moderate - discomfort enough to cause awakenings) and 3 (severe - causing awakenings for most of the night/did not sleep at all).

    Evening (daytime asthma symptoms): 0 (no symptoms), 1 (mild: aware of symptoms that could be easily tolerated), 2 (moderate: discomfort enough to cause interference with daily activity), 3 (severe: incapacitating with inability to work/take part in usual activity).

    Measured: Week 0 (pre-treatment, baseline) to Week 52.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2016 (estimated)
  2. Study start17 Feb 2016
  3. Primary completion17 May 2018
  4. Study completion17 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,155 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02676076
Sponsor's protocol ID
CCD-05993AB1-03
Other IDs
2015-000716-18, 2015
Acronym
TRIMARAN
Status last verified
Jun 2026
First submitted
3 Feb 2016
Last updated
26 Jun 2026
Data monitoring committee
Yes
Individual data sharing
Yes: Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol, and the full Clinical Study Report (CSR), providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared patient-level data is anonymized to protect personally identifiable information. Chiesi access criteria and complete process for clinical data sharing is available on the Chiesi Group website.

Publications

  • Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, Zuccaro F, Vele A, Kots M, Georges G, Petruzzelli S, Canonica GW. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019 Nov 9;394(10210):1737-1749. doi: 10.1016/S0140-6736(19)32215-9. Epub 2019 Sep 30.

    PubMed 31582314

  • Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

    PubMed 36472162

  • Orlovic M, Magni T, Lukyanov V, Guerra I, Madoni A. Cost-effectiveness of single-inhaler extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium in patients with uncontrolled asthma in England. Respir Med. 2022 Sep;201:106934. doi: 10.1016/j.rmed.2022.106934. Epub 2022 Jul 19.

    PubMed 35872377

  • Papi A, Singh D, Virchow JC, Canonica GW, Vele A, Georges G. Normalisation of airflow limitation in asthma: Post-hoc analyses of TRIMARAN and TRIGGER. Clin Transl Allergy. 2022 Apr 17;12(4):e12145. doi: 10.1002/clt2.12145. eCollection 2022 Apr.

    PubMed 35450196

  • Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER. Respir Res. 2020 Oct 29;21(1):285. doi: 10.1186/s12931-020-01558-y.

    PubMed 33121501

  • Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, Papi A. Extrafine triple therapy in patients with asthma and persistent airflow limitation. Eur Respir J. 2020 Sep 24;56(3):2000476. doi: 10.1183/13993003.00476-2020. Print 2020 Sep. No abstract available.

    PubMed 32430414

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing CHF 5993 100/6/12.5 and CHF 1535 100/6 µg in people with Asthma, run by Chiesi Farmaceutici S.p.A. at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

1_Change From Baseline in Pre-Dose Forced Expiratory Volume in the First Second (FEV1) at Week 26 (time frame: Week 0 (pre-treatment, baseline) to Week 26.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02676076, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2026.

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