Short Antibiotic Treatment Versus Duration Guided by Markers of Inflammation in the Treatment of AECOPD (AECOPD)

Evaluation of Two Strategies of Antibiotic Treatment With Levofloxacin in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Short Treatment-versus Treatment Guided by Markers of Inflammation

Chronic obstructive pulmonary disease (COPD) is one of the most common diseases in the world. In a recent study, we showed that administration of levofloxacin is superior to placebo in the treatment of decompensation of COPD; it is accompanied by a substantial reduction in mortality and a significant reduction in the residence time in hospital.

In Tunisia, few data are available on the epidemiology of COPD decompensation. The choice of antibiotic to be used in this situation is challenging to the clinician who must choose between traditional antibiotics (cyclins, aminopenicillins, cotrimoxazole...) and new antimicrobial agents. Recently, it has been emphasized the selection of patients for treatment according to the degree of systemic inflammation (C-Reactive Protein). Indeed, there would have a correlation between the tracheobronchial infection and elevated inflammatory markers. As the elevation of these markers is proportional to the intensity of the inflammatory reaction of the body, is based on the kinetics of these biomarkers in antibiotic treatment seems logical. Thus, C-Reactive Protein allowed not only knowing when to start antibiotics, but also through their kinetic, these markers can guide the duration of therapy and shorten the duration of antibiotic therapy: a rate cut would ensure that the antibiotic treatment was adopted. Available guidelines stated that antibiotic treatment should be maintained at an average of 7 to 10 days while some studies showed no clinical inferiority of courses as short as 3 days. Further reduction of the duration of antibiotherapy was even suggested in order to reduce the risk of adverse events and the pressure that drives bacterial resistance. Hence, we conducted this study using an algorithm to comprehensively evaluate the role of CRP-guided antibiotic prescription in optimizing treatment duration in AECOPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Levofloxacin 500mg

Detailed Description

This study is a prospective, randomized, double blind controlled study including patients admitted to the emergency department (ED) with AECOPD. Patients were randomly assigned (1:1) to receive treatment either according to guidance based on serum CRP level (CRP-guided group) or the standard of care (control group). The randomisation sequence was generated using the sealed envelope sequence generator stratified according to investigator site. Online inclusion of patients according to the concealed sequence was done with an independent, centralised web-based system (DACIMA Tunisia; https://www.dacimasoftware.com).

Patients were assigned to one of the two treatment arms:

1. the intervention (CRP-guided) group: 500 mg (one tablet) of oral levofloxacin daily of levofloxacin for 7 days unless the serum CRP decrease by at least 50% from baseline value. Measurements of serum CRP were done at ED admission, at day-2, day-4 and day-6 and made available to the attending physicians.
2. the standard care (control) group: 500 mg of levofloxacin per day for the first two days. Thereafter, oral tablet of placebo was prescribed according to CRP values as in CRP guided group to keep the blindness of the study. Also, in order to ensure blinding, active drug as well as placebo tablets were encapsulated for identical appearance and placed in sealed envelopes.

The study is approved by ethics committees of all participating centers prior to implementation, and all included patients provided their written informed consent. The study was. The study protocol has been prepared in accordance with the revised Helsinki Declaration for Biomedical Research Involving Human Subjects and Guidelines for Good Clinical Practice.

After verification of inclusion and exclusion criteria as well the informed consent, demographic, clinical and biological data were collected at baseline. These included patient comorbidities, number of exacerbations in the past year, physical examination findings, blood gas analysis, and standard laboratory tests results. Expectorated sputum samples were collected for pathogen culture. All data were recorded in standardized electronic case report forms. All statistical analyses were performed using SPSS software, version 20.0.

• Study Type: Interventional
• Enrollment (Actual): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Tunisia
  • Monastir, Tunisia, 5000
    • Emergency department of university hospital Fattouma Bourguiba of Monastir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients having COPD (according to the definition of the American Thoracic Society) in acute exacerbation

Exclusion Criteria:

• clinical evidence of hemodynamic compromise with the need for vasoactive drugs
• immediate need for mechanical ventilation,
• Glasgow Coma scale <12,
• pneumonia,
• previous adverse reactions to the study drug,
• antibiotic treatment in the previous days,
• pregnancy or lactation,
• severe renal (creatinine clearance 40 mL/min) or hepatic impairment,
• lung disease other than COPD that could affect the clinical evaluation of the treatments. --active alcohol or drug abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The intervention (CRP-guided) group; 500 mg (one tablet) of oral levofloxacin daily of levofloxacin for 7 days unless the serum CRP decrease by at least 50% from baseline value. Measurements of serum CRP were done at ED admission, at day-2, day-4 and day-6 and made available to the attending physicians.	Drug: Levofloxacin 500mg; One tablet per day for 7days.; Other Names: Placebo Levofloxacin 500mg
Experimental: The standard care (control) group; 500 mg of levofloxacin per day for the first two days. Thereafter, oral tablet of placebo was prescribed according to CRP values as in CRP guided group to keep the blindness of the study.	Drug: Levofloxacin 500mg; One tablet per day for 7days.; Other Names: Placebo Levofloxacin 500mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cure rate	By hospital Data and telephonic calling.	1 year after starting protocol

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of additional antibiotherapy course	The frequency of additional antibiotherapy course indicated to treat COPD patients during the hospital stay.	one week
rate of admission in the intensive care unit	By hospital Data and telephonic calling.	one week
exacerbation rate	By hospital Data and telephonic calling.	1 year after starting protocol
exacerbation free interval	rate of admission in the intensive care unit	1year after starting protocol

Collaborators and Investigators

• Sponsor: University of Monastir
• Investigators: Study Director: Semir Nouira, professor, Research Laboratory (LR12SP18) University of Monastir 5000 Tunisia

Publications and helpful links

Helpful Links

• officiel site

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): January 31, 2019

Study Registration Dates

• First Submitted: February 11, 2014
• First Submitted That Met QC Criteria: February 18, 2014
• First Posted (Estimate): February 20, 2014

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 5, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Inflammation; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 CYP1A2 Inhibitors; Anti-Infective Agents, Urinary; Renal Agents; Levofloxacin; Ofloxacin
• Other Study ID Numbers: COPD levofloxacine Study

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