The CATALINA Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Obstructive Pulmonary Disease Exacerbation

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | Death from any cause | Will be assessed during 1 year, on visits 2-6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Exacerbation, Hospitalization