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

Pneumonia Ventilator Associated Clinical Trial

Official title:

Comparison of Two Lengths of Treatment in Early-onset Ventilated Associated Pneumonia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01559753
• Other study ID #: CHUB/GC001
• Status: Completed
• Phase: Phase 4
• First received: November 29, 2011
• Last updated: March 19, 2012
• Start date: January 1998
• Est. completion date: November 2002

Study information

• Verified date: March 2012
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Conseil National de l'Ordre des MédecinsFrance: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 225
• Est. completion date: November 2002
• Est. primary completion date: September 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia Ventilator Associated
• Pneumonia, Ventilator-Associated

Intervention

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)
• 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)

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon	French Society for Intensive Care, GlaxoSmithKline, SmithKline Beecham

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	21 days after inclusion	Yes
Secondary	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.	21 days	Yes