Inhaled Long-acting Bronchodilators With or Without Inhaled Glucocorticosteroids for Preventing Hospitalizations and Death in Elderly Patients With Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Comparison of 1-year Treatment With Inhaled Long Acting Bronchodilators (LABD) Plus Inhaled Glucocorticosteroids (ICS) Versus LABD Without ICS on Re-hospitalizations and/or Death in Elderly Patients With Chronic Obstructive Pulmonary Disease (COPD) Recently Hospitalized Because of an Acute Exacerbation of COPD (ICS-Life Study).

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03662711
• Other study ID #: AIFA-ICSLIFE-001
• Status: Terminated
• Phase: Phase 4
• Start date: November 11, 2018
• Est. completion date: October 26, 2022

Study information

• Verified date: December 2022
• Source: Università degli Studi di Ferrara
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This will be a phase IV, open label, multicenter, randomized pragmatic study in frail elderly patients with COPD. Participants will be treated with either inhaled LABD alone or LABD combined with inhaled glucocorticosteroids. The main aim of the study is to assess whether, in elderly patients with COPD and one or more cardiac comorbidities (heart failure, and/or ischemic heart disease, and/or atrial fibrillation) recently hospitalized because of an acute exacerbation of COPD, 12 months treatment with LABD(s)+ICS can increase the time to first re-hospitalization (all cause) and/or death for any cause when compared with LABD(s) alone. Patients will be followed-up for 3 months after completion of the 12 month treatment period.

Description:

Chronic obstructive pulmonary disease occurs mainly in the elderly and has important comorbidities, particularly cardiovascular, which increase its severity. Chronic obstructive pulmonary disease affects 5% of people globally, increasing to 10% in the elderly. According to data from the World Health Organisation (WHO), there were 384 million cases of COPD in 2010, with a global prevalence of 12% (www.who.int). Deaths due to COPD are 3 million/year globally (GOLD 2018) and >20,000/year in Italy. The investigator speculated that multimorbid elderly COPD patients recently hospitalized due to an acute exacerbation of COPD (AECOPD) and who have concomitant cardiovascular disease may have fewer re-hospitalizations and increased survival in the following year if treated with LABD+ICS rather than with LABD alone. The aim of this study is to examine the efficacy and safety of currently recommended and prescribed inhalation therapies to elderly, frail and multimorbid COPD patients with a recent hospitalization due to an AECOPD. The study involves a group of patients who have never before been selected for a clinical trial and who represent the 5th most common cause of hospitalization and the 3rd most common cause of death in Italy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 843
• Est. completion date: October 26, 2022
• Est. primary completion date: October 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

1. Participant must be older than 60 years of age, at the time of signing the informed consent.

2. Recently (within 6 months) discharged from hospital with a diagnosis of acute exacerbation of COPD (usually coded as Diagnosis Related Group (DRG) 087 or 088).

3. Participants with a clinical diagnosis of COPD (i.e. previous diagnosis of COPD and/or treatment with short acting bronchodilators (SABD), LABD or LABD+ICS

4. Spirometry confirmed diagnosis of COPD, post-bronchodilator (30 minutes after 400 µg salbutamol) FEV1/FVC ratio <0.7. The diagnostic spirometry test can have been performed up to three years prior to randomization, or if never performed before, should be performed not earlier than 4 weeks since last exacerbation

5. Smokers or ex-smokers with a smoking history of >10 pack years (a pack year is defined as 20 cigarettes smoked every day for a year)

6. Clinical diagnosis documented in the patient's medical records of one or more major chronic cardiac disease (heart failure, ischemic heart disease or atrial fibrillation).

7. Currently receiving at least one of the specified treatments (either alone or in combination, see Appendix 10.5) for heart failure, ischemic heart disease or atrial fibrillation.

8. Participant must be willing and able to perform pulmonary function tests

9. Male or female. Contraception is not considered necessary in this cohort of elderly (> 65 years) patients receiving treatment with commercially available licensed products.

10. Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

1. Patients with a primary discharge diagnosis of DRG 087 or DRG 088 but clearly judged by the clinical investigator to be due to other causes, i.e. patients presenting to the hospital with symptoms of AECOPD but due mainly to other conditions (pulmonary embolism, pneumonia, pneumothorax, anemia, acute kidney failure, decompensated heart failure, acute ischemic heart disease, new onset atrial fibrillation, stroke, etc.)

2. Patients who required invasive mechanical ventilation during hospitalization

3. Patients with Asthma as primary and principal diagnosis

4. Patients with severe cardiovascular (CV) disease who in the opinion of the investigator are unlikely to survive the 15 month study period

5. Patients considered unable to comply with the study procedures and follow-up in the opinion of the investigator (eg, evidence of alcohol or drug abuse, psychiatric disorder, physical disability, social or geographical obstacles)

6. Patients in whom spirometry is contraindicated (eg, hemoptysis, detached retina, active tuberculosis, last trimester of pregnancy)

7. Patients with other mechanical or overt causes of respiratory symptoms, particularly dyspnea (such as pneumothorax, chest wall trauma, lung fibrosis, lung cancer, anemia, severe obesity (BMI >40) or cachexia (BMI <18))

8. Patients with any major disease which in the opinion of the investigator would prevent study participation, such as dementia, end-stage disease, cachexia, chronically bedridden patient and life expectancy <15 months.

9. Participation in any other interventional study within the last 3 months or concurrent participation in an observational clinical study.

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Bronchodilator Agents
Fluticasone furoate/vilanterol
• Bronchodilator Agents
Tiotropium
• Bronchodilator Agents
Indacaterol
• Bronchodilator Agents
Umeclidinium/vilanterol
• Bronchodilator Agents
Fluticasone propionate/salmeterol
• Bronchodilator Agents
Beclometasone dipropionate/formoterol
• Bronchodilator Agents
Budesonide formoterol
• Bronchodilator Agents
Glycopyrronium
• Bronchodilator Agents
Aclidinium
• Bronchodilator Agents
Umeclidinium
• Bronchodilator Agents
Formoterol
• Bronchodilator Agents
Indacaterol glycopyrronium
• Bronchodilator Agents
Salmeterol
• Bronchodilator Agents
Tiotropium olodaterol
• Bronchodilator Agents
Aclidinium/formoterol
• Bronchodilator Agents
Olodaterol
• Bronchodilator Agents
Formoterol/glycopyrronium bromide/beclometasone dipropionate
• Bronchodilator Agents
Fluticasone furoate/umeclidinium bromide/vilanterol

Locations

Country	Name	City	State
Italy	Policlinico di Bari, U.O.C. Malattie dell'Apparato Respiratorio Universitaria	Bari	BA
Italy	Ospedale civile di Battipaglia, Medicina, Servizio di Allergologia e Immunologia Clinica	Battipaglia	Campania
Italy	Ospedale Papa Giovanni XXIII	Bergamo	Lombardia
Italy	Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa	Cassano Delle Murge	Puglia
Italy	Azienda Ospedaliero Universitaria "Policlinico Vittorio Emanuele", Pneumologia	Catania	Sicilia
Italy	Dipartimento Di Scienze Mediche e Chirurgiche- Università Magna Grecia	Catanzaro	Calabria
Italy	Ospedale Maggiore, Medicina interna	Chieri	Piemonte
Italy	Ospedale Figlie di San Camillo, Medicina Interna	Cremona	Lombardia
Italy	Ospedale San Giovanni di Dio, UOC Medicina Interna	Crotone	Calabria
Italy	UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO	Ferrara	FE
Italy	Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 1	Firenze	Toscana
Italy	Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 2	Firenze	Toscana
Italy	Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio	Foggia	FG
Italy	Ospedale "Carlo Poma", Struttura Complessa Pneumologia e UTIR	Mantova	Lombardia
Italy	Ospedale "L. Sacco" - Polo Universitario ASST Fatebenefratelli Sacco, Pneumologia	Milano	Lombardia
Italy	Università degli studi di Modena e Reggio Emilia, Clinica Malattie dell'apparato Respiratorio	Modena	Emilia Romagna
Italy	Azienda Ospedaliera dei Colli - Ospedale Monaldi	Napoli	Campania
Italy	Ospedale Monaldi, UOC Clinica Pneumologica	Napoli
Italy	Università degli Studi di Palermo, Ospedale "V. Cervello"	Palermo	Pa
Italy	Azienda Ospedaliero-universitaria di Parma, Clinica pneumologica	Parma	Emilia Romagna
Italy	Fondazione IRCCS Policlinico San Matteo, Pneumologia	Pavia	Lombardia
Italy	Istituti Clinici Scientifici Fondazione Maugeri, Pneumologia Riabilitativa	Pavia	Lombardia
Italy	ASL2 Savonese, Ospedale S. Corona, Pneumologia	Pietra Ligure	Liguria
Italy	Ospedale S. Maria degli Angeli - AAS5 Friuli Occidentale, Pneumologia	Pordenone	Friuli Venezia Giulia
Italy	AUSL - IRCCS di Reggio Emilia, Pneumologia	Reggio Emilia	Emilia Romagna
Italy	Policlinico Universitario Campus Biomedico di Roma, Medicina Interna e Geriatria	Roma	Lazio
Italy	Università di Roma "Tor Vergata", Dipartimento di Medicina dei Sistemi, Malattie dell'apparato respiratorio	Roma	Lazio
Italy	Ospedale di Ceva, Medicina interna	San Bernardino	Piemonte
Italy	Ospedale Civile SS. Annunziata, Medicina interna	Savigliano	Piemonte
Italy	Ospedale San Paolo, Medicina 2 e cure Intermedie	Savona	Liguria
Italy	Università degli studi di Siena, UOC Malattie respiratorie	Siena	Toscana
Italy	Istituti Clinici Scientifici Maugeri S.p.A - SB, Pneumologia Riabilitativa	Telese Terme	Benevento
Italy	Ospedali Riuniti di Ancona, Pneumologia	Torrette	Marche
Italy	Istituti Clinici Scientifici maugeri, Pneumologia Riabilitativa	Tradate	Lombardia
Italy	Ospedale Cà Foncello	Treviso	Veneto
Italy	Ospedale di Cattinara, unità operativa di pneumologia	Trieste	TS
Italy	Policlinico Ospedaliero di Varese - Ospedale di Circolo e Fondazione Macchi, Medicina interna	Varese	Piemonte
Italy	Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa	Veruno	Piemonte
Italy	Ospedale "Jazzolino" ASP, UOC Medicina Interna	Vibo Valentia	Calabria

Sponsors (1)

Lead Sponsor	Collaborator
Università degli Studi di Ferrara

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in forced expiratory volume at one second (FEV1) from baseline to the end of treatment period		12 months
Other	Change in forced vital capacity (FVC) from baseline to the end of treatment period		12 months
Primary	Composite event of the first time to first re-hospitalization and/or death (all cause)		12 months
Secondary	Number of moderate/severe COPD exacerbations in the two patient groups		12 months
Secondary	Number of re-hospitalizations and deaths (all cause) in the two patient groups		12 months
Secondary	Quality of life (QoL) variation measured as change in COPD Assessment Test (CAT) between the two patient groups		12 months
Secondary	QoL variation measured using modified Medical Research Council (mMRC) dyspnoea scale between the two patient groups		12 months
Secondary	Number of pneumonia events		12 months
Secondary	Number of acute cardiac events		12 months
Secondary	Number of cardiovascular events		12 months