Clinical trial NCT03662711: Inhaled Long-acting Bronchodilators With or Without Inhaled Glucocorticosteroids for Preventing Hospitalizations and Death in Elderly Patients With Chronic Obstructive Pulmonary Disease
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).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: adult
drug therapy
combination
bronchodilator agents
male
female
Lead sponsor: Università degli Studi di Ferrara
Sponsor class: OTHER
First posted: 2018-09-07
Enrollment: 843
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite event of the first time to first re-hospitalization and/or death (all cause)
timeFrame: 12 months
Secondary outcomes:
measure: Number of moderate/severe COPD exacerbations in the two patient groups
timeFrame: 12 months
measure: Number of re-hospitalizations and deaths (all cause) in the two patient groups
timeFrame: 12 months
measure: Quality of life (QoL) variation measured as change in COPD Assessment Test (CAT) between the two patient groups
timeFrame: 12 months
measure: QoL variation measured using modified Medical Research Council (mMRC) dyspnoea scale between the two patient groups
timeFrame: 12 months
measure: Number of pneumonia events
timeFrame: 12 months
measure: Number of acute cardiac events
timeFrame: 12 months
measure: Number of cardiovascular events
timeFrame: 12 months
Other outcomes:
measure: Change in forced expiratory volume at one second (FEV1) from baseline to the end of treatment period
timeFrame: 12 months
measure: Change in forced vital capacity (FVC) from baseline to the end of treatment period
timeFrame: 12 months
Locations:
city: Bari
country: Italy
facility: Policlinico di Bari, U.O.C. Malattie dell'Apparato Respiratorio Universitaria
state: BA
city: Telese Terme
country: Italy
facility: Istituti Clinici Scientifici Maugeri S.p.A - SB, Pneumologia Riabilitativa
state: Benevento
city: Catanzaro
country: Italy
facility: Dipartimento Di Scienze Mediche e Chirurgiche- Università Magna Grecia
state: Calabria
city: Crotone
country: Italy
facility: Ospedale San Giovanni di Dio, UOC Medicina Interna
state: Calabria
city: Vibo Valentia
country: Italy
facility: Ospedale "Jazzolino" ASP, UOC Medicina Interna
state: Calabria
city: Battipaglia
country: Italy
facility: Ospedale civile di Battipaglia, Medicina, Servizio di Allergologia e Immunologia Clinica
state: Campania
city: Napoli
country: Italy
facility: Azienda Ospedaliera dei Colli - Ospedale Monaldi
state: Campania
city: Modena
country: Italy
facility: Università degli studi di Modena e Reggio Emilia, Clinica Malattie dell'apparato Respiratorio
state: Emilia Romagna
city: Parma
country: Italy
facility: Azienda Ospedaliero-universitaria di Parma, Clinica pneumologica
state: Emilia Romagna
city: Reggio Emilia
country: Italy
facility: AUSL - IRCCS di Reggio Emilia, Pneumologia
state: Emilia Romagna
city: Ferrara
country: Italy
facility: UNIVERSITà DEGLI STUDI DI FERRARA, CLINICA DI MALATTIE DELL'APPARATO RESPIRATORIO
state: FE
city: Foggia
country: Italy
facility: Università degli studi di Foggia, ospedale pneumologico D'Avanzo, unità operativa di malattie dell'apparato respiratorio
state: FG
city: Pordenone
country: Italy
facility: Ospedale S. Maria degli Angeli - AAS5 Friuli Occidentale, Pneumologia
state: Friuli Venezia Giulia
city: Roma
country: Italy
facility: Policlinico Universitario Campus Biomedico di Roma, Medicina Interna e Geriatria
state: Lazio
city: Roma
country: Italy
facility: Università di Roma "Tor Vergata", Dipartimento di Medicina dei Sistemi, Malattie dell'apparato respiratorio
state: Lazio
city: Pietra Ligure
country: Italy
facility: ASL2 Savonese, Ospedale S. Corona, Pneumologia
state: Liguria
city: Savona
country: Italy
facility: Ospedale San Paolo, Medicina 2 e cure Intermedie
state: Liguria
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII
state: Lombardia
city: Cremona
country: Italy
facility: Ospedale Figlie di San Camillo, Medicina Interna
state: Lombardia
city: Mantova
country: Italy
facility: Ospedale "Carlo Poma", Struttura Complessa Pneumologia e UTIR
state: Lombardia
city: Milano
country: Italy
facility: Ospedale "L. Sacco" - Polo Universitario ASST Fatebenefratelli Sacco, Pneumologia
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo, Pneumologia
state: Lombardia
city: Pavia
country: Italy
facility: Istituti Clinici Scientifici Fondazione Maugeri, Pneumologia Riabilitativa
state: Lombardia
city: Tradate
country: Italy
facility: Istituti Clinici Scientifici maugeri, Pneumologia Riabilitativa
state: Lombardia
city: Torrette
country: Italy
facility: Ospedali Riuniti di Ancona, Pneumologia
state: Marche
city: Palermo
country: Italy
facility: Università degli Studi di Palermo, Ospedale "V. Cervello"
state: Pa
city: Chieri
country: Italy
facility: Ospedale Maggiore, Medicina interna
state: Piemonte
city: San Bernardino
country: Italy
facility: Ospedale di Ceva, Medicina interna
state: Piemonte
city: Savigliano
country: Italy
facility: Ospedale Civile SS. Annunziata, Medicina interna
state: Piemonte
city: Varese
country: Italy
facility: Policlinico Ospedaliero di Varese - Ospedale di Circolo e Fondazione Macchi, Medicina interna
state: Piemonte
city: Veruno
country: Italy
facility: Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa
state: Piemonte
city: Cassano Delle Murge
country: Italy
facility: Istituti Clinici Scientifici Maugeri, Pneumologia Riabilitativa
state: Puglia
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria "Policlinico Vittorio Emanuele", Pneumologia
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 1
state: Toscana
city: Firenze
country: Italy
facility: Azienda Ospedaliero-universitaria Careggi, Medicina per la alta complessità Assistenziale 2
state: Toscana
city: Siena
country: Italy
facility: Università degli studi di Siena, UOC Malattie respiratorie
state: Toscana
city: Trieste
country: Italy
facility: Ospedale di Cattinara, unità operativa di pneumologia
state: TS
city: Treviso
country: Italy
facility: Ospedale Cà Foncello
state: Veneto
city: Napoli
country: Italy
facility: Ospedale Monaldi, UOC Clinica Pneumologica
Study officials:
References: