PROPHY-VAP: Prevention of Early Ventilation Acquired Pneumonia (VAP) in Brain Injured Patients by a Single Dose of Ceftriaxone (PROPHY-VAP)

• ClinicalTrials.gov Identifier: NCT02265406
• Recruitment Status: Completed
• First Posted: October 15, 2014
• Last Update Posted: February 3, 2021
• Sponsor: Poitiers University Hospital
• Information provided by (Responsible Party): Poitiers University Hospital

Tracking Information

• First Submitted Date: October 9, 2014
• First Posted Date: October 15, 2014
• Last Update Posted Date: February 3, 2021
• Actual Study Start Date: October 2015
• Actual Primary Completion Date: July 25, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 14, 2014): Incidence of early VAP, proportion of patients who develop a VAP within the 7 first day after mechanical ventilation (the 7th day included), confirm with microbiological culture, within all included patients. [ Time Frame: 30 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 19, 2017)

• - Incidence of late VAP (> 7 jours) [ Time Frame: 30 months ]
• - Global incidence of VAP during intensive care period (limited to day 60) [ Time Frame: 30 months ]
• - Type of bacteria and their sensitivity for early or late VAP, [ Time Frame: 30 months ]
• - Time between inclusion and occurence of the first VAP (limited to day 28), [ Time Frame: 30 months ]
• - Length of the first period of mechanical ventilation during the intensive care period, [ Time Frame: 30 months ]
• - Time between inclusion and the first spontaneous ventilation test (limited to day 28), [ Time Frame: 30 months ]
• - Length of antibiotherapy during intensive care period, [ Time Frame: 30 months ]
• - Length of intensive care, limited to 60 days, [ Time Frame: 30 months ]
• - Length of stay in intensive care unit, limited to 60 days, [ Time Frame: 30 months ]
• - Length of stay at the hospital, limited to 60 days, [ Time Frame: 30 months ]
• - Neurological prognosis at the discharge of the intensive care unit, [ Time Frame: 30 months ]
• - Mortality at day 28 and 60. [ Time Frame: 30 months ]
• - Incidence of ventilated associated event (limited to day 60) [ Time Frame: 30 months ]
• - Comparison of the global incidence of VAP according to the diagnosis defined by "American Thoracic Society" or by "Centers for Disease Control" [ Time Frame: 30 months ]

Original Secondary Outcome Measures (submitted: October 14, 2014)

• - Incidence of late VAP (> 7 jours) [ Time Frame: 30 months ]
• - Global incidence of VAP during intensive care period (limited to day 60) [ Time Frame: 30 months ]
• - Type of bacteria and their sensivity for early or late VAP, [ Time Frame: 30 months ]
• - Time between inclusion and occurance of the first VAP (limited to day 28), [ Time Frame: 30 months ]
• - Lenght of the first period of mechanical ventilation during the intensive care period, [ Time Frame: 30 months ]
• - Time between inclusion and the first spontaneous ventilation test (limited to day 28), [ Time Frame: 30 months ]
• - Lenght of antibiotherapy during intensive care period, [ Time Frame: 30 months ]
• - Lenght of intensive care, limited to 60 days, [ Time Frame: 30 months ]
• - Lenght of stay in intensive care unit, limited to 60 days, [ Time Frame: 30 months ]
• - Lenght of stay at the hospital, limited to 60 day, [ Time Frame: 30 months ]
• - Neurological prognosis at the discharge of the intensive care unit, [ Time Frame: 30 months ]
• - Mortality at day 28 and 60. [ Time Frame: 30 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PROPHY-VAP: Prevention of Early Ventilation Acquired Pneumonia (VAP) in Brain Injured Patients by a Single Dose of Ceftriaxone
• Official Title: PROPHY-VAP: Prevention of Early Ventilation Acquired Pneumonia (VAP) in Brain Injured Patients by a Single Dose of Ceftriaxone

Brief Summary

Ventilation-associated pneumonia (VAP) is the main site of healthcare-associated infections in the brain injured patients, with an incidence rate of 22% to 58%. VAP increases morbi-mortality, length of stay in intensive care and overall management costs. The prevention of ICU nosocomial infections depends on several measures : orotracheal intubation route, maintaining tube cuff pressure between 25 and 30 cm of water (H2O), maintaining a semi-seated position >= 30°, nasal and oropharyngeal care at regular intervals, striving to avoid unscheduled extubation, and use of a written sedation-analgesia algorithm allowing for early weaning from ventilation. Two randomized study show that administration of antibiotic therapy after intubation reduces the risk of early VAP incidence. However, in clinical practice, its administration solely purposes of limiting VAP occurence is not presently recommended. Indeed, to date no placebo blind controlled study was been realized and the fear of development of bacterial resistance remains stronger than the efficiency of this prevention measure. This aim of the present study is to show by a placebo randomized study that 2g of Ceftriaxone within 8 hours post-intubation after a brain injury decrease the risk of occurence an early VAP.

Ancillary study An ancillary study is performed in 2 centres which routinely practice rectal swabs at admission and discharge of ICU, to survey intestinal flora (CHU of Angers and CHU of Rennes). The goal of this study is to compare the incidence of acquired cephalosporin resistant gram negative bacteria at the discharge of ICU between the 2 groups of patients, receiving or not ceftriaxone.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Early Ventilation Acquired Pneumonia in Brain Injured Patients

Intervention

• Drug: Anti-Infective Agents
• Drug: Placebo

Study Arms

• Experimental: Ceftriaxone
  Intervention: Drug: Anti-Infective Agents
• Placebo Comparator: Sodium Chloride
  Intervention: Drug: Placebo

• Publications *: Dahyot-Fizelier C, Frasca D, Lasocki S, Asehnoune K, Balayn D, Guerin AL, Perrigault PF, Geeraerts T, Seguin P, Rozec B, Elaroussi D, Cottenceau V, Guyonnaud C, Mimoz O; PROPHY-VAP Study group, ATLANREA group. Prevention of early ventilation-acquired pneumonia (VAP) in comatose brain-injured patients by a single dose of ceftriaxone: PROPHY-VAP study protocol, a multicentre, randomised, double-blind, placebo-controlled trial. BMJ Open. 2018 Oct 18;8(10):e021488. doi: 10.1136/bmjopen-2018-021488.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 9, 2020): 354
• Original Estimated Enrollment (submitted: October 14, 2014): 320
• Actual Study Completion Date: July 25, 2020
• Actual Primary Completion Date: July 25, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Brain injured patients with a Glasgow scale score ≤ 12 who require ventilation more than 48 hours

Exclusion Criteria:

• Patient with a high risk of death within the 48 first hours after admission,
• Patient intubated for more than12 hours
• Intubation after the 48th hours after admission
• Coverage to cardiopulmonary arrest
• Coma due to a tumor, an infectious disease or a cardiac arrest
• Previous hospitalisation within the last month before admission for coma
• béta-lactamines allergy
• Patient who receive already antibiotics at the admission for a previous infection
• Prophylactic antibiotic due to be done within 24 hours following the randomisation
• Patient Intubated through a tracheal tube with subglottic secretion aspiration
• Patient with a tracheotomy
• Patient or family refuse to be involved in the study
• Use of Ceftriaxone within 2 days before enrolment
• Participation in another research protocol focusing on an anti-infective treatment or on a measure decreasing the risk of infection
• Patients not affiliated to a social security scheme, Pregnant woman or breast-feeding mother, Patients deprived of their liberty by judicial or administrative decision

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT02265406
• Other Study ID Numbers: PROPHY-VAP
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Poitiers University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Poitiers University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Poitiers University Hospital
• Verification Date: February 2021