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

NCT01559753 | Completed Phase 4

• 1 other identifier: CHUB/GC001
• Study Type: interventional
• Target: 225
• Locations: 0 countries
• Sites: N/A

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

Conditions

Pneumonia Ventilator Associated

Keywords

Antibiotic; treatment; ventilator associated pneumonia; duration

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Rate of secondary infections

  21 days

Study Arms (2)

8 days of antibiotic treatment

EXPERIMENTAL

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; Drug: compare 8 to15 days of antibiotic treatment

15 days antibiotic treatment

ACTIVE COMPARATOR

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

Interventions

Augmentin, Ceftriaxone, Cefotaxime, netilmycin, tobramycin 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)

Also known as: Amoxicillin, Clavulanic acid

8 days of antibiotic treatment

compare 8 to15 days of antibiotic treatment 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)

Also known as: Amoxicillin, Clavulanic acid

15 days antibiotic treatment; 8 days of antibiotic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Refusal to participate
• Lack of informed consent by the patient or his family

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• French Society for Intensive Care: collaborator
• SmithKline Beecham: collaborator
• GlaxoSmithKline: collaborator

Related Publications (1)

• 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.

  PMID: 22952580 DERIVED

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Amoxicillin-Potassium Clavulanate Combination; Ceftriaxone; Cefotaxime; Netilmicin; Tobramycin; Amoxicillin; Clavulanic Acid

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Clavulanic Acids; beta-Lactams; Lactams; Amides; Organic Chemicals; Ampicillin; Penicillin G; Penicillins; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Cephacetrile; Cephalosporins; Thiazines; Sisomicin; Gentamicins; Aminoglycosides; Glycosides; Carbohydrates; Nebramycin; Kanamycin

Study Officials

• Gilles R CAPELLIER, MD, PhD

  Centre Hospitalier Universitaire de Besancon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2011
• First Posted: March 21, 2012
• Study Start: January 1, 1998
• Primary Completion: September 1, 2002
• Study Completion: November 1, 2002
• Last Updated: March 21, 2012

Record last verified: 2012-03