Reduction of Corticosteroid Use in Outpatient Treatment of Exacerbated COPD

Study Overview
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Brief Summary
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Background Chronic obstructive pulmonary disease (COPD) is a major public health issue with no curative treatment. In Switzerland estimated 5-7% of the total population are suffering from this chronic disease. According to current guidelines corticosteroids are part of treatment of acute exacerbations in COPD patients. Several studies suggest that corticosteroids accelerate the recovery of forced expiratory volume in 1 second (FEV1), decrease duration of hospitalization, reduce treatment failure rate and improve clinical outcome. The additional therapeutic benefit on FEV1-recovery tough seems only to last for three to five days. The investigators recently published a hospital-based study showing that in patients presenting to emergency departments with acute exacerbation of COPD, a short five day treatment with systemic steroids was not inferior to a conventional 14 day treatment with regard to re-exacerbation. Cumulative corticosteroid dose could be reduced in this trial. To the investigators knowledge no data is available about the minimal necessary corticosteroid dose in an outpatient treatment setting so far. Aim The primary aim of this study is to investigate in an outpatient setting, whether a three day treatment with orally administered systemic corticosteroids is non-inferior to a five day treatment in acute exacerbation of COPD and if total glucocorticoid exposure can be reduced by shorter therapy. Hypothesis The investigators postulate, that in an outpatient setting, where generally less severe exacerbations are being treated, a three day treatment duration of systemic corticosteroids should be non-inferior to a five day treatment duration with regard to treatment benefits but decrease cumulative corticosteroid exposure. Design and Setting This study is going to be performed as a prospective, randomized, double-blind, placebo-controlled, non-inferiority trial in an outpatient setting. Randomization will be performed as block randomization with a 1:1 allocation. The investigators are going to recruit GPs in northwestern and central Switzerland. Methods The investigators are going to include patients presenting to GP's with acute exacerbation of COPD. When matching the investigators eligibility criteria and written informed consent is given, patients included in the study are receiving systemic corticosteroid treatment (equivalent of 40mg prednisone daily) for either five days (conventional arm) or three days (interventional arm) followed by two days of placebo for the interventional group. Pre-randomized, identically looking, numbered blisters are given to all patients included in the study. Antibiotic treatment (Amoxicillin/Clavulanic acid, 625mg 3/d, for ten days) is given to all patients with a CRP ≥50mg/l, COPD and known diagnosis of bronchiectasis, as well as patients presenting with all three of the following symptoms: change of baseline dyspnea, change of sputum quantity and sputum purulence. Further initial treatment and steroid treatment after inclusion is determined and documented by the GP. Patients will undergo follow-up visits at day three and seven by their GP as well as follow-up phone calls executed by the study center at day 30, 90 and 180.

Official Title
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Reduction of Corticosteroid Use in Outpatient Treatment of Exacerbated COPD - a Randomized, Double-blind, Non-inferiority Study (The RECUT-Trial)

Conditions
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Pulmonary Disease, Chronic Obstructive, Adverse Effect of Glucocorticoids and Synthetic Analogues, Disease Exacerbation

Intervention / Treatment
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* Drug: Placebo
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed Consent as documented by signature Age ≥40 years History of ≥10 pack-years of smoking (past or present smokers) Airway obstruction, defined as FEV1/FVC≤70% Current acute exacerbation of COPD by clinical criteria, defined by the presence of at least two of the following: Change of baseline dyspnea Change of cough Change of sputum quantity or purulence Exclusion Criteria: Diagnosis of asthma Initial necessity of hospitalization Women who are pregnant or breast feeding Premenopausal women with insufficient contraception and anamnestic risk for pregnancy Severe coexisting disease with life expectancy <6 months Diagnosis of tuberculosis Known severe immunosuppression or immunosuppression after solid organ or stem cell transplantation Inability to follow study procedures, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Participation in another study involving an investigational drug Previous enrolment into the current study

Ages Eligible for Study
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Minimum Age: 40 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational treatment<br>Patients included in the placebo group are receiving systemic corticosteroid treatment (equivalent of 40mg prednisone daily) for three days followed by two days of placebo. | Drug: Placebo<br>* Three days prednisone 40mg, two days placebo<br>|
| Active Comparator: Standard treatment<br>Patients included in the control group are receiving systemic corticosteroid treatment (equivalent of 40mg prednisone daily) for five days as recommended in current guidelines. | Drug: Prednisone<br>* Five days prednisone 40mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to next exacerbation |  | Six month follow-up period after index exacerbation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative glucocorticoid dose |  | Six month follow-up period after index exacerbation. | 
| Glucocorticoid side effects and complications |  | Six month follow-up period after index exacerbation. | 
| Change in FEV1 |  | 7 days follow-up period after index exacerbation. | 
| Hospitalization rate during index exacerbation |  | Six month follow-up period after index exacerbation. | 
| Overall mortality |  | Six month follow-up period after index exacerbation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Corticosteroid treatment, COPD, Primary Health Care, Randomized controlled trial