Effectiveness of Antibiotic Therapy for Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease Clinical Trial

— TRANCE  

Official title:

Situations That do Not Require Antibiotics for Acute Exacerbations of Mild-to-moderate Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00495586
• Other study ID #: P06/31
• Status: Completed
• Phase: Phase 4
• First received: July 2, 2007
• Last updated: March 11, 2012
• Start date: October 2007
• Est. completion date: July 2011

Study information

• Verified date: March 2012
• Source: Catalan Society of Family Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Ministry of Health and Consumption
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the effectiveness of antibiotic therapy for patients with acute exacerbations of mild-to-moderate chronic obstructive pulmonary disease.

Description:

Antibiotics are usually prescribed for acute exacerbations of chronic obstructive pulmonary disease (COPD) even though their benefit in mild-to-moderate COPD is not demonstrated. The aim of this study is to assess the effectiveness of antibiotic therapy for exacerbations of COPD, what clinical variables are associated with an improved clinical response with antibiotic therapy with respect to placebo and to identify which patients might recover from an acute exacerbation without antibiotic therapy. Methodology: prospective, randomised, double blind, placebo-controlled clinical trial, in which exacerbations (at least one criterion present: increase of dyspnoea, increase of sputum production and/or increase of purulence) of patients older than 40 yr., smokers or ex-smokers of more than 10 pack-years, with COPD and FEV1 greater than 50%, diagnosed by spirometry and a predicted ratio FEV1/FVC<0.7%. Exclusion criteria: severe COPD (FEV1<50%), active neoplasm, tracheotomy, pneumonia, hospitalization criteria, patients previously being on antibiotics, immunodepressed, history of hypersensitivity to beta-lactams or intolerance to clavulanate, enrollment in other clinical trials, patients who refuse to take part in this study, and patients who have not had a spirometry test for the past two years. Sample size: 677 patients. Interventions: first visit: the patient will be given details of the clinical trial and will be asked to sign informed consent; other data: sputum color, chest X-ray ordered to rule out pneumonia, C-reactive protein levels, and peak flow measurement. The patient will be randomised to receive amoxicillin plus clavulanate or placebo and will be scheduled to return for a 2nd follow-up visit after 3 or 4 days to assess the clinical response and peak flow measurements and to rule out any worsening of the condition. Third visit: scheduled after 9-11 days to assess the clinical response, drug-compliance and peak flow measurement. Fourth visit after 15-20 days for clinical assessment and to observe whether any relapses have occurred. Date of the following exacerbation will be recorded.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: July 2011
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Acute exacerbations (at least one criterion present: increase of dyspnoea, increase of sputum production and/or increase of purulence) of

• patients older than 40 years old,

• smokers or ex-smokers of more than 10 pack-years,

• with COPD and FEV1 greater than 50%, diagnosed by spirometry and a predicted ratio FEV1/FVC<0.7%.

Exclusion Criteria:

• Severe COPD (FEV1<50%)

• Pneumonia

• Active neoplasm

• Tracheotomy

• Criteria for hospitalisation

• Patients previously being on antibiotics

• Immunodepressed patients

• History of hypersensitivity to beta-lactams or intolerance to clavulanate

• Enrollment in other clinical trials

• Patients who refuse to take part in this study

• Patients who have not had a spirometry test for the past two years

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Placebo
One pill to be taken every eight hours for 8 days
• Amoxicillin and clavulanic acid
500-125 mg to be taken every eight hours for 8 days

Locations

Country	Name	City	State
Spain	Hospital Clínic	Barcelona	Catalonia
Spain	Primary Healthcare Center La Marina	Barcelona	Catalonia
Spain	Primary Healthcare Center Figueres	Figueres	Catalonia
Spain	Primary Healthcare Center Girona-4	Girona	Catalonia
Spain	Primary Healthcare Center Montilivi	Girona	Catalonia
Spain	Primary Healthcare Centre Breda-Hostalric	Hostalric	Catalonia
Spain	Primary Healthcare Center Lleida	Lleida	Catalonia
Spain	Primary Healthcare Centre Molins de Rei	Molins de Rey	Catalonia
Spain	Primary Healthcare Centre Olot	Olot	Catalonia
Spain	Primary Healthcare Center Reus-3	Reus	Catalonia
Spain	Primary Healthcare Center Les Muralles	Tarragona	Catalonia
Spain	Primary Healthcare Centre Jaume I	Tarragona	Catalonia
Spain	Primary Healthcare Center Valls Urbà	Valls	Catalonia

Sponsors (2)

Lead Sponsor	Collaborator
Catalan Society of Family Medicine	Fondo de Investigacion Sanitaria

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Who Were Cured	Cure defined as the disappearance of the acute signs and symptoms related to the infection, with complete return to the previous situation of stability	Day 9-11	Yes
Secondary	Number of Days Till the Next Exacerbation	For the assessment of the time till next exacerbation patients were monitored over a period of 365 days on a three-monthly basis. Patients were instructed to contact their physician immediately if there was any change in their health status. Diagnosis of a new exacerbation was based on the same clinical criteria described previously. For the calculation of time to the next exacerbation, all clinical failures occurring during therapy were counted as zero exacerbation-free interval days.	One year	Yes