Nebulized and Intravenous Colistin in Ventilator Associated-pneumonia

NCT02906722 | Terminated Phase 3

• 2 other identifiers: P1309022016-000389-41
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Few antimicrobials are available to treat ventilated associated pneumonia (VAP) caused by Gram negative multi-resistant (MDR) bacteria. Colimycin often remains the only active antibiotic. The aim of the study is to demonstrate the superiority of nebulized colimycin over intravenous colimycin to treat VAP caused by Gramnegative MDR bacteria.

Conditions

Ventilator-associated Pneumonia

Keywords

Nebulized colistin; Intravenous colistin; ventilator-associated pneumonia; multidrug resistance; Gram-negative bacteria

Outcome Measures

Primary Outcomes (1)

• Clinical cure of VAP caused by Gram-negative multidrug resistant bacteria

  Clinical cure is defined as: * resolution of clinical and biological signs of infection and improved radiological signs * and modified clinical pulmonary infection score (CPIS) less than 6 * and negative culture of lower respiratory tract specimen or, successful weaning from invasive mechanical ventilation between day 5 and day 11 * patient colonized with the same pathogen in the respiratory tract is considered as cured, if clinical and biological signs of infection resolved, radiological signs improved, CPIS \< 6 and/or successful weaning from invasive mechanical ventilation has been obtained.

  At end of therapy visit (day11) or before day11 if treatment is considered as failed.

Secondary Outcomes (9)

• Microbiological cure rate

  At end of therapy visit (day11) or before day11 if treatment is considered as failed.

• VAP recurrence rate

  day 28

• Lung superinfection rate

  day 11, day 28

• Mortality

  day 28 and day 90

• Duration of mechanical ventilation

  Participants will be followed for the duration of ICU stay, an expected average of 3 weeks

Other Outcomes (1)

• Colistin plasma concentrations

  from Day 3 and Day 10

Study Arms (2)

Experimental group

EXPERIMENTAL

Patients receive simultaneously nebulized colimycin every 8 h and intravenous placebo administered once, twice or 3 times per day according to renal function

Drug: Intravenous placebo; Drug: Nebulized colimycin

Control group

ACTIVE COMPARATOR

Patients receive simultaneously intravenous colimycin administered once, twice or 3 times per day according to function renal and nebulized placebo every 8 h

Drug: Intravenous colimycin; Drug: Nebulized placebo

Interventions

Intravenous colimycin DRUG

administration once, twice or 3 times per day according to renal function

Control group

Intravenous placebo DRUG

administration once, twice or 3 times per day according to renal function

Experimental group

Nebulized colimycin DRUG

Nebulization is performed with a vibrating plate nebulizer (Aeroneb® Solo) every 8h

Experimental group

Nebulized placebo DRUG

Nebulization is performed with a vibrating plate nebulizer (Aeroneb® Solo) every 8h

Control group

Eligibility Criteria

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

You may qualify if:

• Age older than 18 yr
• Invasive mechanical ventilation for more than 48 h Tracheostomized patients receiving intermittent mechanical ventilation can be included
• VAP caused by Gram-negative MDR bacteria resistant to all β-lactams and fluoroquinolones

You may not qualify if:

• Extrapulmonary Gram-negative MDR infection requiring intravenous colimycin
• VAP associated with bacteremia requiring combined treatment by nebulized and intravenous colimycin
• Hypersensitivity to colistimethate, colistin base, polymyxins and/or their excipients
• Porphyria
• Severe hypoxemia defined as PaO2 / FiO2\< 100; if veno-venous ECMO is initiated, the patient can be included
• Severe brain injury (initial Glasgow coma score \< 8) during the first 7 days before randomization
• Myasthenia
• cystic fibrosis
• Refusal to participate in the study
• No affiliation to social health insurance
• Patient under guardianship
• Pregnancy

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Pitié-Salpêtriere

Paris, 75013, France

Location

Related Publications (4)

• Sole-Lleonart C, Rouby JJ, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, Riera J, Welte T, Roberts JA, Rello J. Intratracheal Administration of Antimicrobial Agents in Mechanically Ventilated Adults: An International Survey on Delivery Practices and Safety. Respir Care. 2016 Aug;61(8):1008-14. doi: 10.4187/respcare.04519. Epub 2016 Mar 8.

  PMID: 26957647 BACKGROUND

• Sole-Lleonart C, Rouby JJ, Blot S, Poulakou G, Chastre J, Palmer LB, Bassetti M, Luyt CE, Pereira JM, Riera J, Felton T, Dhanani J, Welte T, Garcia-Alamino JM, Roberts JA, Rello J. Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults: A Systematic Review and Meta-analysis. Anesthesiology. 2017 May;126(5):890-908. doi: 10.1097/ALN.0000000000001570.

  PMID: 28248714 BACKGROUND

• Rello J, Rouby JJ, Sole-Lleonart C, Chastre J, Blot S, Luyt CE, Riera J, Vos MC, Monsel A, Dhanani J, Roberts JA. Key considerations on nebulization of antimicrobial agents to mechanically ventilated patients. Clin Microbiol Infect. 2017 Sep;23(9):640-646. doi: 10.1016/j.cmi.2017.03.018. Epub 2017 Mar 25.

  PMID: 28347790 BACKGROUND

• Sole-Lleonart C, Roberts JA, Chastre J, Poulakou G, Palmer LB, Blot S, Felton T, Bassetti M, Luyt CE, Pereira JM, Riera J, Welte T, Qiu H, Rouby JJ, Rello J; ESGCIP Investigators. Global survey on nebulization of antimicrobial agents in mechanically ventilated patients: a call for international guidelines. Clin Microbiol Infect. 2016 Apr;22(4):359-364. doi: 10.1016/j.cmi.2015.12.016. Epub 2015 Dec 23.

  PMID: 26723563 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

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

Study Officials

• Qin LU, MD, PhD

  Assistance Publique Hoptiaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: September 20, 2016
• Study Start: July 31, 2017
• Primary Completion: March 27, 2018
• Study Completion: June 19, 2018
• Last Updated: August 13, 2018

Record last verified: 2017-11

Locations

FR (1)