COPD Flare-Up Clinic After Severe Exacerbations (FLARE-COPD)

The Role of COPD Flare-up Clinic Service After Severe Exacerbations to Reduce Recurrent Exacerbations

This prospective randomized controlled trial evaluates whether a specialized "COPD flare-up clinic service" improves outcomes in patients following an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients presenting to the emergency department with AECOPD and discharged or hospitalized will be randomized 1:1 to either structured follow-up in a dedicated flare-up clinic or standard follow-up by scheduled telephone interviews.

We hypothesize that structured follow-up in a specialized clinic will reduce recurrent exacerbations, optimize long-term COPD management, and improve patients' quality of life compared to standard care.

Study Overview

• Status: Not yet recruiting
• Conditions: COPD; COPD Exacerbation (AECOPD)
• Intervention / Treatment: Other: Follow-up in a flare-up clinic

Detailed Description

The primary outcome is to determine whether the flare-up clinic intervention reduces the annualized rate of moderate and severe COPD exacerbations over 12 months. Secondary outcomes include effect of the intervention on the long-term management of COPD and related comorbidities, patients' quality of life, and mortality.

• Randomization // A total of 240 participants with established COPD presenting to the emergency department with an acute exacerbation (AECOPD) will be randomized in a 1:1 ratio to either the intervention or control group. To ensure balance across key clinical pathways, randomization will be stratified by the disposition of the index visit: Emergency Department (ED) discharge versus acute hospitalization. Within each stratum, treatment assignments will be determined using a computer-generated random allocation sequence utilizing variable block sizes of two or four. To prevent selection bias and maintain strict allocation concealment, the randomization schedule will be generated and housed within a secure, centralized electronic system managed exclusively by an independent study coordinator. The clinical research team, including investigators responsible for patient enrollment and clinical care, will remain entirely removed from sequence generation and block determination. Allocation will be revealed sequentially on a patient-by-patient basis only after a participant's eligibility is confirmed and the index visit disposition is finalized.
• Sample size calculation // Based on prior studies, we anticipate that the intervention will reduce the rate of moderate or severe COPD exacerbations by approximately 33% over 12 months, with a clinically meaningful effect considered at 20-25%. Assuming that 60% of patients in the control group will experience at least one exacerbation during this period, a sample size of 95 patients per group is required to achieve 80% power with a two-sided alpha of 0.05. To account for a potential 15-20% loss to follow-up, we plan to enroll 120 patients per group, for a total of 240 participants.

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center, Tel Aviv, 6423906
    • Contact: Ophir Freund, Medical Doctor (Pulmonologist); Phone Number: +972545305648; Email: ophir068@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prior COPD diagnosis based on clinical and spirometry accepted criteria.
• Acute exacerbation of COPD as the main reason for ED arrival.
• Ability to perform in-person and telephone follow-up.
• Agree to participate, with a signed informed consent.

Exclusion Criteria:

• Symptomatic heart failure as the main reason for emergency department visit in the last 6 months.
• Uncontrolled comorbidity.
• Vulnerable Populations: To ensure ethical compliance and participant safety, the study will exclude vulnerable populations. This includes pregnant women, and any person lacking the mental or legal capacity to provide independent informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; The intervention will include 3 follow-up visits in the flare up clinic - the first visit (following randomization) will occur one month after hospital discharge (from ED or admission, baseline), the second at 3 months, and the third visit will be at 12 months from baseline. At 6 and 9 months after inclusion there will be an additional phone-call with structured interview similar to that of the control group. Visits include clinical evaluation, symptom assessment, spirometry, oscillometry, inhaler technique review, cardiovascular risk assessment, and treatment optimization according to GOLD recommendations.	Other: Follow-up in a flare-up clinic; Participants in the intervention arm will attend a specialized "COPD flare-up clinic" for structured follow-up after hospitalization or ED visit due to acute COPD exacerbation. The program includes three in-person clinic visits at 1, 4, and 10 months after the first visit, and two additional structured telephone follow-up at 10 and 18 months. To assess cardiovascular outcomes, a follow-up phone call will be conducted 24 months after Visit 1.
No Intervention: Control; The control group will undergo baseline and 12 months in-person assessments including all questionnaires and physiological tests but without any medical interventions. Structured telephone follow-up at 3, 6, and 9 months will be performed by research coordinators to assess for the study outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Moderate and Severe COPD Exacerbations	Annualized rate of moderate or severe exacerbations of COPD which occurred during the 12-month trial period. Moderate exacerbations require systemic steroids and/or antibiotics, while severe exacerbations lead to hospitalization, ED visit, or death. The rate will be compared between the intervention and control groups. This will be assessed as intention to treat.	From baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe COPD exacerbation rate	The rate of COPD exacerbations leading to hospital arrival between the intervention and control	During study follow-up (12 months from inclusion)
Percentage with any COPD exacerbation	The percentage of patients in each study group with 1 or more COPD exacerbations (moderate or severe)	During study follow-up (12 months from inclusion).
Time to First COPD Exacerbation	Time to first COPD exacerbation between the intervention and control	During study follow-up (12 months from inclusion).
Time to First Hospital Arrival	Time to first hospital arrival due to asthma exacerbation and from any cause between the intervention and control	During study follow-up (12 months from inclusion)
Number of Moderate and Severe COPD Exacerbations (per-protocol)	The annualized rate of moderate or severe COPD exacerbations will be compared between the intervention and control groups using an per-protocol approach. Moderate exacerbations are defined as those requiring treatment with systemic glucocorticoids, antibiotics, or both. Severe exacerbations are defined as those leading to an emergency department visit, hospitalization, or death. Patients excluded from each group will be those lost to follow-up, defined as failing to complete 2 follow-up visits or calls.	12 months from the first follow-up visit
Change in Forced Expiratory Volume in 1 second (FEV1)	FEV1 will be measured using standard spirometry at baseline and at the 12 month follow-up visit. The primary analysis will evaluate the mean change in FEV1 (in liters) from baseline to 12 months between the intervention and control groups using an per-protocol approach.	Spirometry will be performed according to ATS/ERS guidelines, under supervision of trained personnel at baseline and after 12 months.
Oscillometric changes in respiratory resistance at 5 Hz, 20 Hz and the difference between 5 and 20 Hz	Oscillometric change in respiratory resistance at 5 Hz (R5, measured in kPa/L/s) and 20 Hz (R20, measured in kPa/L/s), the difference between R5 and R20 (R5-20, measured in kPa/L/s), and R5-20/R5 - all changes from baseline to 12 months compared between the study groups.	During study follow-up (12 months from inclusion)
Oscillometric changes in area of reactance	Oscillometric changes in area of reactance (AX), measured in KPa/L/s. Changes will be measured from baseline to 12 months and compared between the groups.	During study follow-up (12 months from inclusion)
Respiratory Symptoms Burden Assessed by CAT	Will be evaluated using the COPD Assessment Test (CAT), an eight items patient-administered questionnaire assessing respiratory symptoms, confidence, sleep, and energy levels. The total score ranges from 0 to 40, with higher scores indicating greater symptom burden. We will make 2 analysis - first as intention to treat approach, and then per-protocol.	Assessed from enrollment to 12 months following study initiation.
Respiratory Symptoms Burden Assessed by mMRC Dyspnea Scale	Will be evaluated using the tool mMRC Dyspnea Scale: a patient-reported tool used to assess the degree of baseline breathlessness related to physical activity.	Assessed by a physician at baseline, and subsequent 12 months following study initiation.
Differences In New Diagnoses of Cardiovascular Comorbidities (12 months)	Comparison of new cardiovascular diagnoses between the study groups (rates), including hypertension, diabetes, hyperlipidemia, coronary artery disease and heart failure between the study groups.	From baseline and to 12 months.
Composite of Major Cardiovascular Events	Number of patients experiencing at least one major cardiovascular event, including acute coronary syndrome, stroke, heart failure exacerbation, or death.	During study follow-up (12 months from inclusion).
Composite cardio-pulmonary outcome	Number of patients experiencing at least one major cardiovascular event, including acute coronary syndrome, stroke, or heart failure exacerbation or COPD exacerbation or death.	From inclusion to 12 months
Change in SGRQ	The St. George's Respiratory Questionnaire (SGRQ) is a standardized questionnaire used to measure health-related quality of life in patients with COPD. Scores range from 0 to 100, with higher socres indicating worse outcome. This outcome will assess changes from baseline to 12 months between the two groups.	From baseline to 12 months

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: AstraZeneca

Publications and helpful links

General Publications

• Chapman KR, Bourbeau J, Rance L. The burden of COPD in Canada: results from the Confronting COPD survey. Respir Med. 2003 Mar;97 Suppl C:S23-31. doi: 10.1016/s0954-6111(03)80022-7.
• Agusti A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, Bourbeau J, Han MK, Martinez FJ, Montes de Oca M, Mortimer K, Papi A, Pavord I, Roche N, Salvi S, Sin DD, Singh D, Stockley R, Lopez Varela MV, Wedzicha JA, Vogelmeier CF. Global Initiative for Chronic Obstructive Lung Disease 2023 Report: GOLD Executive Summary. Eur Respir J. 2023 Apr 1;61(4):2300239. doi: 10.1183/13993003.00239-2023. Print 2023 Apr.
• Lindenauer PK, Pekow P, Gao S, Crawford AS, Gutierrez B, Benjamin EM. Quality of care for patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 2006 Jun 20;144(12):894-903. doi: 10.7326/0003-4819-144-12-200606200-00006.
• Parums DV. Editorial: Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 Guidelines for COPD, Including COVID-19, Climate Change, and Air Pollution. Med Sci Monit. 2023 Oct 1;29:e942672. doi: 10.12659/MSM.942672.
• Nici L, Mammen MJ, Charbek E, Alexander PE, Au DH, Boyd CM, Criner GJ, Donaldson GC, Dreher M, Fan VS, Gershon AS, Han MK, Krishnan JA, Martinez FJ, Meek PM, Morgan M, Polkey MI, Puhan MA, Sadatsafavi M, Sin DD, Washko GR, Wedzicha JA, Aaron SD. Pharmacologic Management of Chronic Obstructive Pulmonary Disease. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 May 1;201(9):e56-e69. doi: 10.1164/rccm.202003-0625ST.
• Bar-Shai A, Freund O, Ovdat T, Segel MJ, Klempfner R, Elis A. Management of acute COPD exacerbations in the internal medicine departments in Israel-a national survey. Front Med (Lausanne). 2023 Aug 24;10:1174148. doi: 10.3389/fmed.2023.1174148. eCollection 2023.
• Kitchlu A, Abdelshaheed T, Tullis E, Gupta S. Gaps in the inpatient management of chronic obstructive pulmonary disease exacerbation and impact of an evidence-based order set. Can Respir J. 2015 May-Jun;22(3):157-62. doi: 10.1155/2015/587026. Epub 2015 Apr 17.
• Choi PP, Day A, Etchells E. Gaps in the care of patients admitted to hospital with an exacerbation of chronic obstructive pulmonary disease. CMAJ. 2004 Apr 27;170(9):1409-13. doi: 10.1503/cmaj.1030713.
• Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002 Oct;57(10):847-52. doi: 10.1136/thorax.57.10.847.
• Anzueto A. Impact of exacerbations on COPD. Eur Respir Rev. 2010 Jun;19(116):113-8. doi: 10.1183/09059180.00002610.

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 1, 2026
• First Submitted That Met QC Criteria: June 1, 2026
• First Posted (Actual): June 5, 2026

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: COPD exacerbation; COPD management; COPD flare-up
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 0690-25-TLV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No