Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated: The AGATE Multicenter Randomized Controlled Study.

BACKGROUND: Ventilator-associated pneumonia (VAP) is the most frequent health care-associated infection in severely ill patients, and aspiration of contaminated oropharyngeal content around the cuff of the tracheal tube is the main route of contamination. RESEARCH QUESTION: Is continuous regulation of tracheal cuff pressure using a pneumatic device superior to manual assessment three times daily using a portable manometer (routine care) in preventing VAP in patients with severe trauma? STUDY DESIGN AND METHODS: In this open-label, randomized controlled superiority trial conducted in 13 French ICUs, adults (age ≥ 18 years) with severe trauma (Injury Severity Score > 15) and requiring invasive mechanical ventilation for ≥ 48 h were enrolled. Patients were randomly assigned (1:1) via a secure Web-based random number generator in permuted blocks of variable sizes to one of two groups according to the method of tracheal cuff pressure control. The primary outcome was the proportion of patients developing VAP within 28 days following the tracheal intubation, as determined by two assessors masked to group assignment, in the modified intention-to-treat population. This study is closed to new participants. RESULTS: A total of 434 patients were recruited between July 31, 2015, and February 15, 2018, of whom 216 were assigned to the intervention group and 218 to the control group. Seventy-three patients (33.8%) developed at least one episode of VAP within 28 days following the tracheal intubation in the intervention group compared with 64 patients (29.4%) in the control group (adjusted subdistribution hazard ratio, 0.96; 95% CI, 0.76-1.20; P = .71). No serious adverse events related to the use of the pneumatic device were noted. INTERPRETATION: Continuous regulation of cuff pressure of the tracheal tube using a pneumatic device was not superior to routine care in preventing VAP in patients with severe trauma. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02534974; URL: www.clinicaltrials.gov.

Skin antisepsis with chlorhexidine-alcohol versus povidone iodine-alcohol, combined or not with use of a bundle of new devices, for prevention of short-term peripheral venous catheter-related infectious complications and catheter failure: an open-label, single-centre, randomised, four-parallel group, two-by-two factorial trial: CLEAN 3 protocol study.

INTRODUCTION: Short peripheral intravenous catheters (PVCs) are the most frequently used invasive medical devices in hospitals. Unfortunately, PVCs often fail before the end of treatment due to the occurrence of mechanical, vascular or infectious complications, which prolongs hospitalisation and increases healthcare costs and mortality.Prevention of these complications is mainly based on the respect of hygiene rules and the use of biocompatible catheters. In critically ill patients, 2% chlorhexidine-alcohol is superior to 5% povidone iodine-alcohol for skin preparation before central venous and arterial catheters; whether this finding can be extended to PVC inserted in the wards remains speculative. Similarly, the use of new technologies such as catheters designed to minimise blood exposure, zero-reflux needleless connectors, disinfecting caps and flushing PVCs before and after each medication administration to maintain catheter patency are of theoretical interest to prevent PVC failure, but little scientific data support their routine use. METHODS AND ANALYSIS: The CLEAN 3 study is an open-label, single-centre, randomised, two-by-two factorial trial. One thousand patients visiting our emergency department and requiring hospital admission in the wards will be randomised to one of four strategies according to skin preparation and devices used. The two primary endpoints will be (1) the incidence of infectious complications related to the catheters (colonisation, local infection or bloodstream infection) and (2) the time between catheter insertion and catheter failure defined as any premature removal of PVC before end of treatment, other than for routine replacement. ETHICS AND DISSEMINATION: This protocol has been approved by an independent ethics committee and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: EudraCT 2018-A02535-50; NCT03757143.

Multicentre randomised controlled trial to investigate the usefulness of continuous pneumatic regulation of tracheal cuff pressure for reducing ventilator-associated pneumonia in mechanically ventilated severe trauma patients: the AGATE study protocol.

INTRODUCTION: Severe trauma represents the leading cause of mortality worldwide. While 80% of deaths occur within the first 24 hours after trauma, 20% occur later and are mainly due to healthcare-associated infections, including ventilator-associated pneumonia (VAP). Preventing underinflation of the tracheal cuff is recommended to reduce microaspiration, which plays a major role in the pathogenesis of VAP. Automatic devices facilitate the regulation of tracheal cuff pressure, and their implementation has the potential to reduce VAP. The objective of this work is to determine whether continuous regulation of tracheal cuff pressure using a pneumatic device reduces the incidence of VAP compared with intermittent control in severe trauma patients. METHODS AND ANALYSIS: This multicentre randomised controlled and open-label trial will include patients suffering from severe trauma who are admitted within the first 24 hours, who require invasive mechanical ventilation to longer than 48 hours. Their tracheal cuff pressure will be monitored either once every 8 hours (control group) or continuously using a pneumatic device (intervention group). The primary end point is the proportion of patients that develop VAP in the intensive care unit (ICU) at day 28. The secondary end points include the proportion of patients that develop VAP in the ICU, early (≤7 days) or late (>7 days) VAP, time until the first VAP diagnosis, the number of ventilator-free days and antibiotic-free days, the length of stay in the ICU, the proportion of patients with ventilator-associated events and that die during their ICU stay. ETHICS AND DISSEMINATION: This protocol has been approved by the ethics committee of Poitiers University Hospital, and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials NCT02534974.

Comparison of four skin preparation strategies to prevent catheter-related infection in intensive care unit (CLEAN trial): a study protocol for a randomized controlled trial.

BACKGROUND: Catheter-related infection is the third cause of infections in intensive care units (ICU), increasing the length of stay in ICU and hospital, mortality, and costs. Skin antisepsis is one of the most prevalent preventive measures. In this respect, it would appear preferable to recommend the use of alcoholic povidone iodine or chlorhexidine rather than aqueous povidone iodine. However, the data comparing chlorhexidine to povidone-iodine, both of them in alcoholic solutions, remain limited. Moreover, the benefits of enhanced cleaning prior to disinfection of skin that is not visibly soiled have yet to be confirmed in a randomized study. METHODS: A prospective multicenter, 2 × 2 factorial, randomized-controlled, assessor-blind trial will be conducted in 11 intensive care units in six French hospitals. All adult patients aged over 18 years requiring the insertion of at least one peripheral arterial catheter and/or a non-tunneled central venous catheter and/or a hemodialysis catheter and/or an arterial pulmonary catheter will be randomly assigned to have all their catheters cared with one of four skin preparation strategies (2% chlorhexidine/70% isopropyl alcohol or 5% povidone iodine/69% ethanol with or without prior skin scrubbing). At catheter removal, catheter tips will be quantitatively cultured. Sets of aerobic and anaerobic blood cultures will be routinely obtained when a patient has fever, hypothermia, or other indications. In case of suspected catheter-related infection the patient's form will be reviewed by an independent adjudication committee. We plan to enroll 2,400 patients (4,800 catheters). The main objective is to demonstrate that use of 2% alcoholic chlorhexidine compared to 5% alcoholic povidone iodine in skin preparation lowers the rate of catheter-related infection. The second endpoint is to demonstrate that enhanced skin cleaning prior to disinfection of skin that is not visibly soiled does not reduce catheter colonization. Other outcomes include comparison of skin colonization at catheter insertion site, comparison of catheter colonization and catheter-related bacteremia taking place during implementation of the four strategies of skin preparation, and cutaneous tolerance, length of hospitalization, mortality, and costs. DISCUSSION: This study will help to update recommendations on the choice of an antiseptic agent to use in skin preparation prior to insertion of a vascular catheter and, by extension, of an epidural catheter and it will likewise help to update recommendations on the usefulness of skin scrubbing prior to disinfection when the skin is not visibly soiled. TRIAL REGISTRATION: Clinicaltrials.gov number NCT01629550.