Antibiotic/COPD in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD) Requiring Mechanical Ventilation

Antibiotic Comparison Exacerbation COPD

Although the use of antibiotics in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is largely accepted, controversy remains regarding whether the choice of antibiotic has any impact on outcome. Our aim was to compare the effects of the combination of trimethoprim and sulfamethoxazole and ciprofloxacin in patients treated for severe COPD exacerbation requiring mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: Sepsis; Chronic Obstructive Pulmonary Disease; Antibiotics
• Intervention / Treatment: Drug: ciprofloxacin; Drug: trimethoprim-sulfamethoxazole

Detailed Description

Antibiotic therapy has been shown to be beneficial in patients with severe acute exacerbation of chronic obstructive pulmonary disease (COPD). Although recent guidelines support the use of new antibiotics there is no evidence that newer antibiotics are any better than older agents. The choice of antibiotic to be used in this situation is challenging to the clinician who must choose between traditional antibiotics (cyclins, aminopénicillins, cotrimoxazole...) and new antimicrobial agents. Indeed, available comparative studies did not show an obvious superiority of new antibiotics compared to their predecessors . Taking into account bacterial agents associated to COPD exacerbations, one must choose an antibiotic which has the best activity against Haemophilus influenzae, Streptococcus pneumoniae and Branhamella catarrhalis. News quinolones are represented as an interesting alternative to standard antibiotics because of their large spectrum of action and of their pharmacokinetic advantages allowing high tissue penetration in the pulmonary parenchyma and tracheobronchial tree. Data on their use among patients having moderate exacerbation of COPD are encouraging but their effectiveness in more severe presentations is not established. The objective of this randomized controlled and double blind study is to evaluate the effectiveness and tolerance of ciprofloxacin compared to trimethoprim sulfamethoxazole in patients admitted to ICU for severe exacerbation of COPD requiring mechanical ventilation.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients having a COPD (according to the definition of the American Thoracic Society) and having an acute exacerbation leading to an acute respiratory failure requiring the admission to ICU and mechanical ventilation.
• The acute exacerbation of COPD is defined by increase in the frequency of cough, the volume and the purulence of expectoration and increase of baseline dyspnea. To be included, patients must have respiratory rate >30 cycles/min and one of the following blood gas criteria (with blood gases performed right before the initiation of mechanical ventilation): PaC02 > 6kPa and arterial pH <7.30.

Exclusion Criteria:

• Pneumonia documented with chest radiography
• Antibiotic treatment in the ten previous days of ICU admission
• Former inclusion in the study
• History of allergy to the quinolones and/or to trimethoprim sulfamethoxazole
• Pregnancy or breast feeding
• Severe chronic disease: heart, liver, kidney.
• Known immunodeficiency (malignant hemopathy, AIDS...)
• Digestive disease which could affect the absorption of the drugs
• Concomitant infection which requires systemic antibiotic treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ciprofloxacin; 750 mg a day during 10 days	Drug: ciprofloxacin; 1500 mg a day for 10 days; Other Names: fluoroquinolone
Active Comparator: trimethoprim-sulfamethoxazole; 2000 mg a day for 10 days	Drug: trimethoprim-sulfamethoxazole; 2000 mg a day for 10 days; Other Names: bactrim; sulfatrim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Two major criteria will be used for the determination of sample size and the estimate of the effectiveness of the treatments of the study: 1. mortality (in ICU and in the hospital) 2. rate of additional antibiotherapy course.	The decision to initiate new antibiotics was left to the discretion of the treating physician, and if resistant species were cultured, the protocol treatment was not systematically changed unless the clinical course of the patient worsened	30 day after starting protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mechanical ventilation duration	duration of mechanical ventilation	30 days after starting protocol
Duration of hospital stay	duration of hospital stay	30 days after starting protocol

Collaborators and Investigators

• Sponsor: University of Monastir
• Investigators: Principal Investigator: nouira semir, MD, research unit 04/UR/08-20

Publications and helpful links

General Publications

• Nouira S, Marghli S, Besbes L, Boukef R, Daami M, Nciri N, Elatrous S, Abroug F. Standard versus newer antibacterial agents in the treatment of severe acute exacerbation of chronic obstructive pulmonary disease: a randomized trial of trimethoprim-sulfamethoxazole versus ciprofloxacin. Clin Infect Dis. 2010 Jul 15;51(2):143-9. doi: 10.1086/653527.

Study record dates

Study Major Dates

• Study Start: July 1, 2002
• Primary Completion (Actual): June 1, 2005
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: November 12, 2008
• First Submitted That Met QC Criteria: November 13, 2008
• First Posted (Estimate): November 14, 2008

Study Record Updates

• Last Update Posted (Actual): February 24, 2020
• Last Update Submitted That Met QC Criteria: February 20, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: antibiotic; chronic obstructive pulmonary disease; pulmonary infection
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Ciprofloxacin; Fluoroquinolones; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination
• Other Study ID Numbers: 04/UR/08-20