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

November 29, 2011
March 19, 2012
January 1998
September 2002   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01559753 on ClinicalTrials.gov Archive Site
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.
Same as current
Not Provided
Not Provided
 
Early-onset Ventilator-associated Pneumonia in Adults: Comparison of 8 Versus 15 Days of Antibiotic Treatment
Comparison of Two Lengths of Treatment in Early-onset Ventilated Associated Pneumonia

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

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.
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Pneumonia Ventilator Associated
  • 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
  • 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
    Interventions:
    • Drug: Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin
    • Drug: compare 8 to15 days of antibiotic treatment
  • 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.
    Intervention: Drug: compare 8 to15 days of antibiotic treatment
Capellier G, Mockly H, Charpentier C, Annane D, Blasco G, Desmettre T, Roch A, Faisy C, Cousson J, Limat S, Mercier M, Papazian L. Early-onset ventilator-associated pneumonia in adults randomized clinical trial: comparison of 8 versus 15 days of antibiotic treatment. PLoS One. 2012;7(8):e41290. doi: 10.1371/journal.pone.0041290. Epub 2012 Aug 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
225
November 2002
September 2002   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01559753
CHUB/GC001
No
Centre Hospitalier Universitaire de Besancon
Centre Hospitalier Universitaire de Besancon
  • French Society for Intensive Care
  • SmithKline Beecham
  • GlaxoSmithKline
Principal Investigator: Gilles R CAPELLIER, MD, PhD Centre Hospitalier Universitaire de Besancon
Centre Hospitalier Universitaire de Besancon
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP