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

Primary Purpose

Pneumonia Ventilator Associated

Status
Completed
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin
compare 8 to15 days of antibiotic treatment
Sponsored by
Centre Hospitalier Universitaire de Besancon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pneumonia Ventilator Associated focused on measuring Antibiotic, treatment, ventilator associated pneumonia, duration

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    8 days of antibiotic treatment

    15 days antibiotic treatment

    Arm Description

    Patients will receive a combination antibiotic during 5 days and then 3 days of a single Beta Lactam antibiotic

    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.

    Outcomes

    Primary Outcome Measures

    Cure of respiratory infection
    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
    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.

    Full Information

    First Posted
    November 29, 2011
    Last Updated
    March 19, 2012
    Sponsor
    Centre Hospitalier Universitaire de Besancon
    Collaborators
    French Society for Intensive Care, SmithKline Beecham, GlaxoSmithKline
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01559753
    Brief Title
    Early-onset Ventilator-associated Pneumonia in Adults: Comparison of 8 Versus 15 Days of Antibiotic Treatment
    Official Title
    Comparison of Two Lengths of Treatment in Early-onset Ventilated Associated Pneumonia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2012
    Overall Recruitment Status
    Completed
    Study Start Date
    January 1998 (undefined)
    Primary Completion Date
    September 2002 (Actual)
    Study Completion Date
    November 2002 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Centre Hospitalier Universitaire de Besancon
    Collaborators
    French Society for Intensive Care, SmithKline Beecham, GlaxoSmithKline

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    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
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Pneumonia Ventilator Associated
    Keywords
    Antibiotic, treatment, ventilator associated pneumonia, duration

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    Participant
    Allocation
    Randomized
    Enrollment
    225 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    8 days of antibiotic treatment
    Arm Type
    Experimental
    Arm Description
    Patients will receive a combination antibiotic during 5 days and then 3 days of a single Beta Lactam antibiotic
    Arm Title
    15 days antibiotic treatment
    Arm Type
    Active Comparator
    Arm Description
    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 Type
    Drug
    Intervention Name(s)
    Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin
    Other Intervention Name(s)
    Amoxicillin, Clavulanic acid
    Intervention Description
    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)
    Intervention Type
    Drug
    Intervention Name(s)
    compare 8 to15 days of antibiotic treatment
    Other Intervention Name(s)
    Amoxicillin, Clavulanic acid
    Intervention Description
    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)
    Primary Outcome Measure Information:
    Title
    Cure of respiratory infection
    Description
    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.
    Time Frame
    21 days after inclusion
    Secondary Outcome Measure Information:
    Title
    Rate of secondary infections
    Description
    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.
    Time Frame
    21 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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: Ongoing curative antibiotic therapy 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) 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Gilles R CAPELLIER, MD, PhD
    Organizational Affiliation
    Centre Hospitalier Universitaire de Besancon
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22952580
    Citation
    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.
    Results Reference
    derived

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

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