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

NCT ID: NCT01559753

Last Updated: 2012-03-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 225 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-01-31
• Study Completion Date: 2002-11-30

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.

Conditions

Pneumonia Ventilator Associated

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

8 days of antibiotic treatment

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

Group Type: EXPERIMENTAL

Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin

Intervention Type: DRUG

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)

compare 8 to15 days of antibiotic treatment

Intervention Type: DRUG

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)

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.

Group Type: ACTIVE_COMPARATOR

compare 8 to15 days of antibiotic treatment

Intervention Type: DRUG

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)

Interventions

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)

Intervention Type: 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)

Intervention Type: DRUG

Other Intervention Names

Amoxicillin; Clavulanic acid; Amoxicillin; Clavulanic acid

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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

French Society for Intensive Care

OTHER

Sponsor Role: collaborator

SmithKline Beecham

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Besancon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles R CAPELLIER, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Besancon

References

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.

Reference Type: DERIVED

PMID: 22952580 (View on PubMed)

Other Identifiers

CHUB/GC001

Identifier Type: -

Identifier Source: org_study_id