Early-onset Ventilator-associated Pneumonia in Adults: Comparison of 8 Versus 15 Days of Antibiotic Treatment

This study has been completed.
Sponsor:
Collaborators:
French Society for Intensive Care
SmithKline Beecham
GlaxoSmithKline
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier:
NCT01559753
First received: November 29, 2011
Last updated: March 19, 2012
Last verified: March 2012
  Purpose

The duration of treatment of community acquired pulmonary infection varies between 5 and 14 days according to the authors (22), or even 3 days with new drugs having long half-life (2). For nosocomial pulmonary infection, treatment durations are not standardized (5). It is simply mentioned the concept of "usual" treatment of at least 15 days. However, recent studies used 10 days of treatment without significant decrease in the rate of healing compared to usual treatment. It is essential to clarify the optimal duration of antibiotic treatment. Indeed, any excessive extension of treatment may increase the occurrence of adverse effects (renal toxicities, hepatic...), and induce resistance of bacteria to antibiotics (selection pressure), colonization of the patient by Multiresistant bacteria and an increase in the cost of treatment


Condition Intervention Phase
Pneumonia Ventilator Associated
Drug: Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin
Drug: compare 8 to15 days of antibiotic treatment
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Comparison of Two Lengths of Treatment in Early-onset Ventilated Associated Pneumonia

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Besancon:

Primary Outcome Measures:
  • Cure of respiratory infection [ Time Frame: 21 days after inclusion ] [ Designated as safety issue: Yes ]
    The primary endpoint of the present study was the clinical cure rate at day 21. Complete clinical recovery was determined by the absence of the following criteria: death, septic shock (except when associated with a documented non-respiratory infection), intercurrent adverse event attributable to the protocol (or for which attributability to the protocol could not be ruled out) requiring modified antibiotic treatment, and patients who relapsed.


Secondary Outcome Measures:
  • Rate of secondary infections [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    The study focused on establishing incidence of secondary nosocomial infections; number of patients on antibiotic treatment; total number of days of antibiotic treatment; duration of MV; number of patients still under ventilation; number of patients still in ICU; length of stay in ICU on day 21; and mortality rate at 3 months.


Enrollment: 225
Study Start Date: January 1998
Study Completion Date: November 2002
Primary Completion Date: September 2002 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 8 days of antibiotic treatment
Patients will receive a combination antibiotic during 5 days and then 3 days of a single Beta Lactam antibiotic
Drug: Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin

All patients included in the study will be treated by a combination of antibiotics during the first 5 days, then by monotherapy for either 3 or 10 days according to their allocated group.

  • Beta-Lactams:

    • Amoxicillin + clavulanic Acid : 2 g TDS for 3 days, then 1 g TDS
    • Ceftriaxone : 2 g OD during 3 days, then 1 g OD
    • Cefotaxime : 2 g TDS during 3 days, then 1 g TDS
  • Aminoglycosides

    • Tobramycin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
    • Netilmicin : loading dose of 10 mg/kg OD, then 8 mg/kg OD (adaptation in case of renal failure)
    • Dibekacin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
Other Names:
  • Amoxicillin
  • Clavulanic acid
Drug: compare 8 to15 days of antibiotic treatment

All patients included in the study will be treated by a combination of antibiotics during the first 5 days, then by monotherapy for either 3 or 10 days according to their allocated group.

Beta-Lactams:

  • Amoxicillin + clavulanic Acid : 2 g TDS for 3 days, then 1 g TDS
  • Ceftriaxone : 2 g OD during 3 days, then 1 g OD
  • Cefotaxime : 2 g TDS during 3 days, then 1 g TDS

Aminoglycosides

  • Tobramycin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
  • Netilmicin : loading dose of 10 mg/kg OD, then 8 mg/kg OD (adaptation in case of renal failure)
  • Dibekacin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
Other Names:
  • Amoxicillin
  • Clavulanic acid
Active Comparator: 15 days antibiotic treatment
All patients included in the study will be treated by a combination of antibiotics during the first 5 days, then by monotherapy for 10 days according to the group. The beta-lactam antibiotics will be administered in high doses during the first 3 days of treatment. Aminoglycosides will be administered in a single daily dose, with a loading dose the first day of treatment.
Drug: compare 8 to15 days of antibiotic treatment

All patients included in the study will be treated by a combination of antibiotics during the first 5 days, then by monotherapy for either 3 or 10 days according to their allocated group.

Beta-Lactams:

  • Amoxicillin + clavulanic Acid : 2 g TDS for 3 days, then 1 g TDS
  • Ceftriaxone : 2 g OD during 3 days, then 1 g OD
  • Cefotaxime : 2 g TDS during 3 days, then 1 g TDS

Aminoglycosides

  • Tobramycin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
  • Netilmicin : loading dose of 10 mg/kg OD, then 8 mg/kg OD (adaptation in case of renal failure)
  • Dibekacin : loading dose of 6 mg/kg OD, then 5 mg/kg OD (adaptation in case of renal failure)
Other Names:
  • Amoxicillin
  • Clavulanic acid

Detailed Description:

This is a prospective, randomized, open, multi-center study.

3.1 Primary Objective

Show that antibiotic therapy of 8 or 15 days is equivalent in terms of clinical cure rates in the treatment of early onset nosocomial pulmonary infection in patients under mechanical ventilation.

3.2 Secondary Objective

  • Study of nosocomial infections: assessing the influence of the duration of antibiotic treatment on the rate of fatal pulmonary and extra-pulmonary infection (definition of nosocomial infections: annex XIII).

    • Study of bacterial Ecology: research of changes in the flora of the gut under treatment and analysis of pathological samples (antibiotic resistance phenotypes +/-genotypes).

  • Economic Survey: analyze the costs related to the treatment of nosocomial pneumonia and its complications in two study groups.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Early onset nosocomial pneumonia in patients under mechanical ventilation since at least 24 h Patients aged 18 years or more The patient must be able to receive either one of the two arms of treatment defined for the study Information on the patient and his family informed consent obtained during the first three days Bacteria sensitive to the specified antibiotic regimen

Exclusion Criteria:

  • Patients do not match the criteria for inclusion
  • 18 years of age, pregnant Patients
  • Another infectious outbreak documented the day of the BAL.
  • Patients with acquired immunosuppression (blood diseases, HIV,...), induced (immunosuppressive drugs, cancer, radiation therapy) or congenital.
  • Steroids for a period exceeding 15 days.
  • Leukopenia (1000 GB/mm (or neutropenia (500 PN/mm)
  • Purulent pleural effusion, pulmonary abscess
  • Cystic fibrosis
  • Antibiotic treatment according to the following terms:

    1. Ongoing curative antibiotic therapy
    2. Antibiotics within 3 days before the diagnosis of VAP, except surgical antibiotic prophylaxis (defined according to the consensus conference "antibiotic prophylaxis in the surgical environment in adult" December 11, 1992) (27)
    3. Use of antibiotics not authorized in the study (see list)
  • Allergy to antibiotics used in the study
  • Inclusion in another study assessing antibiotic treatment, either the treatment or prevention of nosocomial pulmonary disease
  • Refusal to participate
  • Lack of informed consent by the patient or his family
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559753

Sponsors and Collaborators
Centre Hospitalier Universitaire de Besancon
French Society for Intensive Care
SmithKline Beecham
GlaxoSmithKline
Investigators
Principal Investigator: Gilles R CAPELLIER, MD, PhD Centre Hospitalier Universitaire de Besancon
  More Information

No publications provided by Centre Hospitalier Universitaire de Besancon

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Centre Hospitalier Universitaire de Besancon
ClinicalTrials.gov Identifier: NCT01559753     History of Changes
Other Study ID Numbers: CHUB/GC001
Study First Received: November 29, 2011
Last Updated: March 19, 2012
Health Authority: France: Conseil National de l'Ordre des Médecins
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé

Keywords provided by Centre Hospitalier Universitaire de Besancon:
Antibiotic
treatment
ventilator associated pneumonia
duration

Additional relevant MeSH terms:
Pneumonia
Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Amoxicillin
Anti-Bacterial Agents
Tobramycin
Cefotaxime
Cefoxitin
Ceftriaxone
Clavulanic Acids
Clavulanic Acid
Netilmicin
Amoxicillin-Potassium Clavulanate Combination
Beta-Lactams
Antibiotics, Antitubercular
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antitubercular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014