The CATALINA Study

Chronic Obstructive Pulmonary Disease Exacerbation Clinical Trial

Official title:

A European Multi-centre Prospective Cohort Study in Patients Hospitalized for an Acute Exacerbation of COPD

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05008081
• Other study ID #: S64324
• Status: Recruiting
• Start date: October 25, 2022
• Est. completion date: December 2026

Study information

• Verified date: November 2023
• Source: KU Leuven
• Contact: Kristina Vermeersch, PhD
• Phone: 016342284
• Email: kristina.vermeersch[@]kuleuven.be
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The CATALINA study is a prospective cohort study embedded within CICERO (Collaboration In COPD ExaceRbatiOns, a European Respiratory Society supported Clinical Research Collaboration), designed to collect standardised, longitudinal clinical data and biological samples in 20 centres across Europe.

Description:

The initial objective is to recruit 1000 patients hospitalised for an acute COPD exacerbation by the end of CICERO's first lifecycle (3 years), from whom 1 year follow-up data and biological samples will be collected. By doing so, CICERO aims to develop a comprehensive European COPD patient data- and biobank phenotyped in relation to the exacerbation, to support the development of future EU-wide clinical intervention trials in COPD for specific patient subgroups, as well as new prognostication tools for COPD exacerbations.

The clinical data and biological samples will be obtained during 6 scheduled study visits, during the hospitalization period of the index acute exacerbation as well as the outpatient setting after hospital discharge; and 3 additional unscheduled study visits should the patient be readmitted for respiratory reasons during study participation (i.e. first readmission only).

• 3 study visits will be scheduled during the hospitalization period of the index acute exacerbation:

• visit 1: within 48h of hospital admission, study inclusion (Day 1)

• visit 2: at 72h after study inclusion (Day 3)

• visit 3: at hospital discharge, at investigator's discretion (Day X)

• 3 study visits will be scheduled during the outpatient setting:

• visit 4: at 3 months after study inclusion (Day 90)

• visit 5: at 6 months after study inclusion (Day 180)

• visit 6: at 12 months after study inclusion (Day 365)

• The first hospital readmission for respiratory reasons during the patient's study participation will undergo the same testing schedule as mandated during the hospitalization period of the index event:

• unscheduled visit 1: within 48h of first hospital readmission

• unscheduled visit 2: within 72h of first hospital readmission

• unscheduled visit 3: at hospital discharge for first hospital readmission

Resulting from CICERO's future lifecycles will be the continued expansion of the data- and bio-bank, both in cohort size and duration of follow-up.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: December 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age 18 years and older

• Established diagnosis of COPD by medical doctor (based on clinical history OR pulmonary function test with an FEV1/FVC < 0.7)

• Current hospitalization with suspicion of an acute exacerbation of COPD (AECOPD)

• Inclusion within 48 hours post hospital admission

• Voluntary written informed consent of the participant or his/her representative obtained prior to any study procedure

Exclusion Criteria:

• Patients unwilling or unable to comply with study procedures

• Patients not requiring treatment with systemic corticosteroids, antibiotics or both as a minimum therapy for the index AECOPD

• Patients with a confirmed positive test result for COVID19, or those highly suspected based on clinical examination

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
Belgium	CHU St-Pierre Brussels	Brussels
Belgium	UZ Leuven	Leuven
Belgium	CHU UCL Namur Site Godinne	Yvoir
France	CHU de Lille	Lille
France	Cochin Hospital	Paris
Germany	LungenClinic	Großhansdorf
Germany	Klinikum Itzehoe	Itzehoe
Germany	University Medical Centre of Gießen & Marburg	Marburg
Italy	University Hospital of Ferrara	Ferrara
Netherlands	UMC Groningen	Groningen
Netherlands	Maastricht University Medical Hospital	Maastricht
Spain	Hospital Clinic de Barcelona	Barcelona
Sweden	Sahlgrenska University Hospital	Gothenburg
United Kingdom	Glenfield Hospital	Leicester
United Kingdom	Guy's Saint Thomas	London
United Kingdom	Royal Brompton Hospital	London
United Kingdom	Churchil Hospital	Oxford

Sponsors (4)

Lead Sponsor	Collaborator
Wim Janssens	AstraZeneca, European Respiratory Society, Roche Pharma AG

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Italy,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality	Death from any cause	Will be assessed during 1 year, on visits 2-6
Secondary	Step-up in hospital care for respiratory reasons	A composite outcome measure defined as: New hospitalization for respiratory reasons; Hospital care intensification from baseline (ie. within 24h from hospital admission) for respiratory reasons, including: 2.1 Non-invasive respiratory therapy (oxygen by mask or nasal flow); 2.2 Non-invasive respiratory therapy (oxygen by NIV or high flow); 2.3 Invasive respiratory therapy (intubation and mechanical ventilation); 2.4 Physiological support with inotropes	Will be assessed during 1 year, on visits 2-6
Secondary	Treatment intensification for respiratory reasons	A composite outcome measure defined as: Prolongation of systemic corticosteroids >5 days administered for the index acute exacerbation or first readmission for respiratory reasons; Upgrade of antibiotics administered for the index exacerbation or first readmission for respiratory reasons; New course of systemic corticosteroids for respiratory reasons; New course of antibiotics for respiratory reasons	Will be assessed during 1 year, on visits 2-6
Secondary	Treatment failure	A composite outcome measure defined as: All-cause mortality; Step-up in hospital care for respiratory reasons; Treatment intensification for respiratory reasons	Will be assessed during 1 year, on visits 2-6
Secondary	Severe treatment failure	As intensification of drug treatment regimens and treatment intensifications are country/region-specific and not always related to failure of disease control, severe treatment failure (STF) will be defined as the composite of: All-cause mortality; Step-up in hospital care for respiratory reasons	Will be assessed during 1 year, on visits 2-6
Secondary	Readmission for a severe COPD exacerbation	Readmission of the patient to the hospital for a severe COPD exacerbation	Will be assessed during 1 year, on visits 2-6
Secondary	New hospitalization for respiratory reasons	New admission of the patient to the hospital for respiratory reasons	Will be assessed during 1 year, on visits 2-6
Secondary	Hospital care intensification for respiratory reasons	A composite outcome measure defined as: Non-invasive respiratory therapy (oxygen by mask or nasal flow); Non-invasive respiratory therapy (oxygen by NIV or high flow); Invasive respiratory therapy (intubation and mechanical ventilation); Physiological support with inotropes	Will be assessed during 1 year, on visits 2-6
Secondary	Time to	The time to the following outcomes will be measured: All-cause mortality; First hospital readmission for respiratory reasons; Hospital care intensification for respiratory reasons; Treatment intensification for respiratory reasons; Treatment failure; Severe treatment failure	Will be assessed during 1 year, on visits 2-6
Secondary	Number of participants with a new or changed Do Not Resuscitate (DNR) code	The implementation of a new or changed DNR code during study participation will be measured.; DNR 0: do not restrict therapy (i.e. explicit statement not to withhold any life-sustaining interventions); DNR 1: do not resuscitate, further specified as: DNR 1a: No CPR DNR 1b: No CPR + no intubation + NIV to be considered; DNR 2: do not extend therapy (i.e. no CPR + no intubation + no NIV); DNR 3: discontinue therapy (i.e. no CPR + no intubation + no NIV + withdrawal of current treatment°); Abbreviations: CPR, cardiopulmonary resuscitation; NIV, non-invasive ventilation; °, treatment of disabling symptoms to be prioritised, however, no life-prolonging interventions are to be continued	Will be assessed during 1 year, on visits 2-6
Secondary	Cumulative dose of systemic corticosteroids	The total dose of systemic corticosteroids administered during study participation will be measured.	Will be assessed during 1 year, on visits 2-6
Secondary	Total days in hospital	Total number of days spent in a hospital during study participation will be measured.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in modified Medical Research Council (mMRC): a dyspnea scale	The change in the following patient reported outcome measures (PROM) will be measured: modified Medical Research Council (mMRC): a dyspnea scale; scale: 0 to 4; interpretation: higher scores indicate worse outcome	Will be assessed during 1 year, on visits 2-6
Secondary	Change in COPD Assessment Test (CAT): a COPD impact scale	The change in the following patient reported outcome measures (PROM) will be measured: COPD Assessment Test (CAT): a COPD impact scale; scale: 0 to 40; interpretation: higher scores indicate worse outcome	Will be assessed during 1 year, on visits 2-6
Secondary	Change in Patient Health Questionnaire-9 (PHQ-9): a depression scale	The change in the following patient reported outcome measures (PROM) will be measured: Patient Health Questionnaire-9 (PHQ-9): a depression scale; scale: 0 to 29; interpretation: higher scores indicate worse outcome	Will be assessed during 1 year, on visits 2-6
Secondary	Change in Generalized Anxiety Disorder-7 (GAD-7): an anxiety scale	The change in the following patient reported outcome measures (PROM) will be measured: Generalized Anxiety Disorder-7 (GAD-7): a anxiety scale; scale: 0 to 21; interpretation: higher scores indicate worse outcome	Will be assessed during 1 year, on visits 2-6
Secondary	Change in patient reported experience measure (PREM)	The change in the following PREM will be measured: 1. Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS): measuring patients' perceptions of their hospital experience; -interpretation: higher scores indicate better outcome	Will be assessed during 1 year, on visits 2-6
Secondary	Change in comorbidities	Changes in baseline comorbidies (ie. the appearance of new or worsening of existing) will be measured	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker Eotaxin-3 (CCL26)	Eotaxin-3 is a small cytokine belonging to the CC chemokine family (called CCL26, Chemokine (C-C motif) ligand 26). Eotaxin-3 is chemotactic for eosinophils and basophils and elicits its effects by binding to the cell surface chemokine receptor CCR3.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker IL-5	Interleukin-5 (IL-5) acts on mature eosinophils, leading to proliferation, activation, differentiation, and survival; playing a critical role in the host immune response to infections.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker IL-33	Interleukin-33 (IL-33) is described as an inducer of type 2 immune responses, activating T helper 2 cells and mast cells.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker MCP-4 (CCL13)	Monocyte chemotactic protein 4 (MCP-4), also called CCL13, is a major chemo-attractant for eosinophils, basophils, monocytes and T lymphocytes	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker TARC4 (CCL17)	Thymus and activation regulated chemokine (TARC), also known as CCL17, is a chemokine that induces chemotaxis of Type 2 T helper (Th2) cells.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker IP-10 (CXCL10)	Interferon gamma-induced protein 10 (IP-10 (CXCL10)) chemoattracts Th1 lymphocytes and monocytes, and inhibits cytokine-stimulated hematopoietic progenitor cell proliferation.	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker IL1A	Interleukin 1 alpha (IL1A) stimulates the activity of genes involved in inflammation and immunity	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker IL-8	Interleukin 8 (IL-8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells; which attracts and activates neutrophils in inflammatory regions	Will be assessed during 1 year, on visits 2-6
Secondary	Change in biomarker GM-CSF	Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates proliferation and/or activation of monocytes, macrophages, neutrophils and eosinophils	Will be assessed during 1 year, on visits 2-6

External Links

•   ERJ Editorial 2020 - The CICERO (Collaboration In COPD ExaceRbatiOns) Clinical Research Collaboration
•   ERJ Open Research 2023 - Patients' Acceptance of Outcome and Experience Measurements During Hospitalisation for COPD Exacerbations: A Cicero CRC - ELF Online Patient Survey
•   Int J COPD 2021 - Standardisation of Clinical Assessment, Management and Follow-Up of Acute Hospitalised Exacerbation of COPD: A Europe-Wide Consensus
•   The CICERO website
•   The ERS - CICERO CRC webpage