Active Controlled Trial of CHF5993 Pressurized Metered-dose Inhaler ( pMDI) vs Symbicort®Turbuhaler® in Patients With Chronic Obstructive Pulmonary Disease ( COPD) (TRIVERSYTI)

NCT03197818 | Completed Phase 3 Results DMC

• 4 other identifiers: CCD-5993AA1-14TaiwanSouth KoreaCTR20160507
• Study Type: interventional
• Target: 708
• Locations: 3 countries
• Sites: 64

Brief Summary

Primary Objective

• To demonstrate the superiority of CHF 5993 pressurised metered dose inhaler (pMDI) over Symbicort® Turbuhaler® in terms of pulmonary function (change from baseline in pre-dose morning forced expiratory volume in the first second of a forced vital capacity manoeuvre \[FEV1\] and 2-hour post-dose morning FEV1 at Week 24). Secondary Objectives Key secondary objective:
• To demonstrate the superiority of CHF 5993 pMDI over Symbicort® Turbuhaler® in terms of pulmonary function (change from baseline in pre-dose morning FEV1 and 2-hour post-dose morning FEV1 at Week 24) in the subgroup of Chinese population. Other secondary objectives:
• To evaluate the effect of CHF 5993 pMDI on other lung function parameters, patient's health status and clinical outcome measures;
• To collect data in order to assess the impact of study treatments on health economic outcomes;
• To assess the safety and the tolerability of the study treatments.

Conditions

COPD (Chronic Obstructive Pulmonary Disease)

Keywords

COPD; Anticholinergics; Triple Combination; CHF 5993 pMDI; Symbicort® Turbuhaler®

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Pre-dose Forced Expiratory Volume Within the First Second (FEV1) at Week 24

  FEV1 measures the amount, or volume, exhaled by a patient in the first second of the expiration after a full inspiration. The lower the values, more severe the airflow limitation. For FEV1, the highest value from 3 technically acceptable attempts was recorded irrespective of the curve they were derived from. The chosen highest value had not to exceed the second highest by more than 150 mL; if the difference was larger, up to 8 measurements were performed and the largest value reported. Please note that the adjusted mean is reported with its 95%IC.

  Week 24 (Visit 6)

• Change From Baseline in 2-hour Post-dose FEV1 at Week 24

  FEV1 measures the amount, or volume, exhaled by a patient in the first second of the expiration after a full inspiration. The lower the values, more severe the airflow limitation. For FEV1, the highest value from 3 technically acceptable attempts was recorded irrespective of the curve they were derived from. The chosen highest value had not to exceed the second highest by more than 150 mL; if the difference was larger, up to 8 measurements were performed and the largest value reported. Please note that the adjusted mean is reported with its 95%IC.

  Week 24 (Visit 6)

Secondary Outcomes (23)

• Change From Baseline in Pre-dose Morning FEV1 at All the Other Clinic Visits

  Pre-dose morning at week 4 (visit 3), week 12 (visit 4), week 18 (visit 5), week 24 (visit 6)

• Change From Baseline at 2-hour Post-dose FEV1 at All the Clinic Visits

  2-hour post-dose morning at week 0 (V2), week 4 (V3), week 12 (V4), week 18 (V5), week 24 (V6)

• Change From Baseline in Pre-dose FEV1 ≥ 100 mL at Week 24

  Week 24 (V6)

• Changes From Pre-Dose to the 2-Hour Post-Dose Value of FEV1 at Each Visit From Visit 3 Onwards

  Week 4 (V3), week 12 (V4), week 18 (V5), week 24 (V6)

• Adjusted Rate Per Patient Per Year of Moderate or Severe COPD Exacerbations Over 24 Weeks of Treatment

  Over the 24-week treatment period

Study Arms (2)

CHF 5993 100/6/12.5 µg

EXPERIMENTAL

Fixed combination of extrafine beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg plus glycopyrronium bromide 12.5 µg (BDP/FF/GB), 2 inhalations bid, for a total daily dose of 400/24/50 μg BDP/FF/GB respectively, administered via pMDI. If patients were used to inhaling their pMDI COPD medications with a spacer device, the AeroChamber PlusTM was used with the study pMDI treatments, dispensed to the patients at V2 (Week 0) and V4 (Week 12).

Drug: CHF 5993 100/6/12.5 µg

Symbicort Turbuhaler 160/4.5 µg

ACTIVE COMPARATOR

Fixed combination of 160 µg budesonide (BUD) + 4.5 µg formoterol fumarate (FF), 2 inhalations a day, for a total daily dose of 640/18 μg BUD/FF respectively, administered via dry powder inhaler (DPI).

Drug: 160 µg budesonide + 4.5 µg formoterol fumarate

Interventions

CHF 5993 100/6/12.5 µg DRUG

Fixed combination of extrafine beclometasone dipropionate 100 µg plus formoterol fumarate 6 µg plus glycopyrronium bromide 12.5 µg / metered dose

Also known as: BDP/FF/GB, beclometasone dipropionate / formoterol fumarate / glycopyrronium bromide

CHF 5993 100/6/12.5 µg

160 µg budesonide + 4.5 µg formoterol fumarate DRUG

Fixed combination of budesonide 160 µg plus formoterol fumarate 4.5 µg

Also known as: BUD/FF, Budesonide / formoterol fumarate

Symbicort Turbuhaler 160/4.5 µg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female adults aged ≥ 40 years with written informed consent obtained prior to any study-related procedure;
• Patients with a diagnosis of COPD (according to GOLD 2015 strategic document, updated January 2015) at least 12 months before the screening visit;
• A smoking history of at least 10 pack years \[pack years = (number of cigarettes per day x number of years)/20\]. Current and ex-smokers were eligible; Note: Smoking cessation therapy had to be completed 6 months prior to screening visit.
• A post-bronchodilator FEV1 \< 50% of the predicted normal value and a post-bronchodilator FEV1/FVC ratio \< 0.7 at least 10-15 mins after 4 puffs (4 x 100 μg) of salbutamol pMDI;
• A documented history of at least one exacerbation in the 12 months preceding the screening visit. COPD exacerbation was defined according to the following: "A sustained worsening of the patient's condition (dyspnoea, cough and/or sputum production/purulence), from the stable state and beyond normal day-to-day variations, that is acute in onset and necessitates a change in regular medication in a patient with underlying COPD that includes prescriptions of systemic corticosteroids and/or antibiotics or need for hospitalisation";
• Patients under therapy for at least 2 months prior to screening with either:
• ICS/LABA or
• ICS/LAMA or
• Inhaled LABA and inhaled LAMA or
• LAMA or
• LABA.
• A cooperative attitude and ability to be trained to use correctly the study treatment inhalers (pMDI and Turbuhaler®);
• A cooperative attitude and ability to be trained to use correctly the COPD questionnaires.

You may not qualify if:

• If a patient met any of the following criteria, he/she was not enrolled into the study:
• Pregnant or lactating women and all women physiologically capable of becoming pregnant (i.e. women of childbearing potential) UNLESS are willing to use one or more of the following reliable methods of contraception:
• Placement of an intrauterine device or intrauterine system;
• Hormonal contraception (implantable, patch, oral);
• Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical vaults/caps) with spermicidal foam/gel/film/cream/suppository;
• Male sterilisation (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). Reliable contraception had to be maintained throughout the study until last study visit. "True abstinence" was acceptable only if it was in line with the preferred and usual lifestyle of the patient. Pregnancy testing was carried out during the course of the study in all women of childbearing potential: serum pregnancy test was performed at screening (V1) and end of treatment (V6); and urine pregnancy test was performed at all visits except V0 and V6.
• Any postmenopausal women (physiologic menopause defined as "12 consecutive months of amenorrhea") or women permanently sterilised (e.g. tubal occlusion, hysterectomy or bilateral salpingectomy) could have been enrolled in the study;
• Diagnosis of asthma, history of allergic rhinitis or atopy (atopy which may raise contra-indications or impact the efficacy of the study according to Investigator's judgement);
• Patients requiring use of the following medications:
• Systemic steroids for COPD exacerbation in the 4 weeks prior to screening;
• A course of antibiotics for COPD exacerbation longer than 7 days in the 4 weeks prior to screening;
• Phosphodiesterase E (PDE) inhibitors in the 4 weeks prior to screening;
• Use of antibiotics for a lower respiratory tract infection (e.g. pneumonia) in the 4 weeks prior to screening;
• COPD exacerbation requiring prescriptions of systemic corticosteroids and/or antibiotics or hospitalisation during the run-in period;
• Changes in dose, schedule, formulation or product of oral xanthine derivatives (e.g. theophylline) in the month prior to screening visit or during the run-in period. Stop of xanthines prior to screening visit was allowed;

Sponsors & Collaborators

• Chiesi Farmaceutici S.p.A.: lead

Study Sites (64)

Chiesi clinical Trial Site 156031

Beijing, Beijing Municipality, 100000, China

Location

Chiesi Clinical Trial Site 156026

Beijing, Beijing Municipality, 100020, China

Location

Chiesi clinical Trial Site 156017

Beijing, Beijing Municipality, 100029, China

Location

Chiesi Clinical Trial Site 156012

Beijing, Beijing Municipality, 100144, China

Location

Chiesi Clinical Trial Site 156045

Chongqing, Chongqing Municipality, 400000, China

Location

Chiesi Clinical Trial Site 156002

Fuzhou, Fujian, 350005, China

Location

Chiesi clinical Trial Site 156024

Foshan, Guangdong, 528000, China

Location

Chiesi Clinical Trial Site 156048

Guangzhou, Guangdong, 510000, China

Location

Chiesi Clinical Trial Site 156013

Guangzhou, Guangdong, 510080, China

Location

Chiesi Clinical Trial Site 156008

Zhanjiang, Guangdong, 524000, China

Location

Chiesi Clinical Trial site 156003

Nanning, Guangxi, 530021, China

Location

Chiesi clinical Trial Site 156020

Haikou, Hainan, 570100, China

Location

Chiesi Clinical Trial Site 156044

Shijiangzhuang, Hebei, 050000, China

Location

Chiesi Clinical Trial Site 156040

Changsha, Hunan, 410000, China

Location

Chiesi Clinical Trial Site 156043

Baotou, Inner Mongolia, 014000, China

Location

Chiesi Clinical Trial Site 156015

Baotou, Inner Mongolia, 014010, China

Location

Chiesi Clinical Trial Site 156004

Huai'an, Jiangsu, 223300, China

Location

Chiesi clinical Trial Site 156033

Jiangyin, Jiangsu, 320281, China

Location

Chiesi clinical Trial Site 156022

Nanjing, Jiangsu, 210006, China

Location

Chiesi Clinical Trial Site 156047

Jiujiang, Jiangxi, 332000, China

Location

Chiesi Clinical Trial Site 156041

Nanchang, Jiangxi, 330000, China

Location

Chiesi clinical Trial Site 156028

Nanchang, Jiangxi, 330006, China

Location

Chiesi Clinical Trial Site 156042

Pingxiang, Jiangxi, 337000, China

Location

Chiesi clinical Trial Site 156023

Changchun, Jilin, 130000, China

Location

Chiesi Clinical Trial Site 156036

Changchun, Jilin, 130000, China

Location

Chiesi clinical Trial Site 156019

Changchun, Jilin, 130021, China

Location

Chiesi Clinical Trial Site 156007

Shenyang, Liaoning, 110004, China

Location

Chiesi clinical Trial Site 156025

Yinchuan, Ningxia, 750000, China

Location

Chiesi Clinical Trial Site 156014

Shanghai, Shanghai Municipality, 200025, China

Location

Chiesi clinical Trial Site 156037

Shanghai, Shanghai Municipality, 200031, China

Location

Chiesi Clinical Trial Site 156005

Shanghai, Shanghai Municipality, 200072, China

Location

Chiesi Clinical Trial Site 156006

Shanghai, Shanghai Municipality, 200433, China

Location

Chiesi Clinical Trial Site 156011

Shanghai, Shanghai Municipality, 200433, China

Location

Chiesi Clinical Trial Site 156038

Shanghai, Shanghai Municipality, 210009, China

Location

Chiesi Clinical Trial Site 156039

Taiyuan, Shanxi, 030001, China

Location

Chiesi clinical Trial Site 156035

Chengdu, Sichuan, 610000, China

Location

Chiesi Clinical Trial Site 156010

Chengdu, Sichuan, 610041, China

Location

Chiesi clinical Trial Site 156032

Chongqing, Sichuan, 400000, China

Location

Chiesi clinical Trial Site 156034

Tianjin, Tianjin Municipality, 300052, China

Location

Chiesi clinical Trial Site 156018

Hangzhou, Zhejiang, 310014, China

Location

Chiesi Clinical Trial Site 156046

Linhai, Zhejiang, 317000, China

Location

Chiesi Clinical Trial Site 156001

Guangzhou, 510230, China

Location

Chiesi Clinical Trial Site 410003

Chuncheon, Gang'weondo, 24289, South Korea

Location

Chiesi Clinical Trial Site 410012

Bucheon-si, Gyeonggido, 14584, South Korea

Location

Chiesi Clinical Trial Site 410001

Bucheon-si, Gyeonggido, 420-717, South Korea

Location

Chiesi Clinical Trial Site 410002

Goyang-si, Gyeonggido, 10380, South Korea

Location

Chiesi Clinical Trial Site 410005

Jeonju, Jeonrabugdo, 54907, South Korea

Location

Chiesi Clinical Trial Site 410008

Seoul, Seoul Teugbyeolsi, 07345, South Korea

Location

Chiesi Clinical Trial Site 410007

Seoul, Seoul Teugbyeolsi, 07985, South Korea

Location

Chiesi Clinical Trial Site 410004

Seoul, Seoul Teugbyeolsi, 100-032, South Korea

Location

Chiesi Clinical Trial Site 410006

Seoul, Seoul Teugbyeolsi, 136-705, South Korea

Location

Chiesi Clinical Trial Site 410009

Gyeonggi-do, Seoul Teugbyeols, 135-720, South Korea

Location

Chiesi Clinical Trial Site 410010

Daegu, Ulsan, 705-703, South Korea

Location

Chiesi Clinical Trial Site 410011

Seoul, 04401, South Korea

Location

Chiesi Clinical Trial Site 410013

Seoul, 2559, South Korea

Location

Chiesi Clinical Trial Site 410014

Seoul, 5030, South Korea

Location

Chiesi Clinical Trial Site 158001

Keelung, Keelung Municipality, 204, Taiwan

Location

Chiesi Clinical Trial Site 158004

Kaohsiung City, Penghu, 83301, Taiwan

Location

Chiesi Clinical Trial Site 158003

Douliu, Yunlin, 64041, Taiwan

Location

Chiesi Clinical Trial Site 158010

Changhua, 500, Taiwan

Location

Chiesi Clinical Trial Site 158006

Kaohsiung City, 824, Taiwan

Location

Chiesi Clinical Trial Site 158008

Taichung, Taiwan

Location

Chiesi Clinical Trial Site 158005

Taipei, 11217, Taiwan

Location

Chiesi Clinical Trial Site 158011

Taipei, 220, Taiwan

Location

Related Publications (1)

• Zheng J, Baldi S, Zhao L, Li H, Lee KH, Singh D, Papi A, Grapin F, Guasconi A, Georges G. Efficacy and safety of single-inhaler extrafine triple therapy versus inhaled corticosteroid plus long-acting beta2 agonist in eastern Asian patients with COPD: the TRIVERSYTI randomised controlled trial. Respir Res. 2021 Mar 23;22(1):90. doi: 10.1186/s12931-021-01683-2.

  PMID: 33757520 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Beclomethasone; Formoterol Fumarate; Glycopyrrolate; Budesonide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Chlorinated; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Quaternary Ammonium Compounds; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnenediones; Pregnenes

Limitations and Caveats

The TRIVERSYTI study was impacted in its later stage by the COVID-19 pandemic. The study conduct was adapted shortly after the breakthrough of the pandemic to ensure the safety of the patients and staff as well as the study continuity. Additionally, the monitoring activities were impacted by the partial or total lockdown at country level as a result of the global spread of COVID-19.Specific process for performing and reporting of Remote Visits was followed due to COVID spread.

Results Point of Contact

• Title: Clinical Trial INFO
• Organization: Chiesi Farmaceutici S.p.A.

clinicaltrials_info@chiesi.com

+39 0521 2791

Study Officials

• Jinping Zheng

  The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2017
• First Posted: June 23, 2017
• Study Start: December 14, 2016
• Primary Completion: May 26, 2020
• Study Completion: May 26, 2020
• Last Updated: May 27, 2026
• Results First Posted: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

TW (8); CN (42); KR (14)