Koeman 2006.

Methods	Study design: A multicentre randomised double‐blind placebo‐controlled trial with 3 parallel groups Location: 2 university hospitals and 3 general hospitals in the Netherlands Number of centres: 5 hospitals (2 surgical and 5 mixed ICUs) Study period: February 2001 to March 2003 Funding source: ZONMw Netherlands Organization for Health Research and Development (project number 2200.0046)
Participants	Inclusion criteria: Consecutive adult patients (> 18 years of age) needing mechanical ventilation for at least 48 hours were included within 24 hours after intubation and start of mechanical ventilation Exclusion criteria: A pre‐admission immunocompromised status, pregnancy, and if the physical condition did not allow oral application of study medication Age group: Not stated Number randomised: 385 Number evaluated: 379 Group A: Chlorhexidine group: n = 127; mean age: 60.9 ± 15.3; M/F: 71/57; APACHE II: 22.2 ± 7.02 Group B: Chlorhexidine/COL group: n = 128; mean age: 62.4 ± 19.1; M/F: 66/61; APACHE II: 23.7 ± 7.38 Group C: Control group: n = 130; mean age: 62.1 ± 15.9; M/F: 93/37; APACHE II: 21.8 ± 7.43
Interventions	Comparison: Chlorhexidine (in petroleum jelly) versus petroleum jelly alone Group A: Chlorhexidine group (n = 127): Oral decontamination with chlorhexidine (2%) in Vaseline petroleum jelly Group B: Chlorhexidine/COL group (n = 128): Oral decontamination with chlorhexidine plus colistin antibiotic chlorhexidine/colistin (CHX/COL 2%/2%) in Vaseline petroleum jelly Group C: Control (n = 130): Oral decontamination with Vaseline petroleum jelly Trial medication was administered 4 times daily, after removing remnants of the previous dose with a gauze moistened with saline. Approximately 2 cm of paste, approximately 0.5 g, was put on a gloved fingertip and administered to each side of the buccal cavity
Outcomes	The following outcome variables were reported for each group: 1. Incidence of VAP 2. Incidence of early onset VAP 3. Days ventilated (mean ± SD) 4. ICU stay (mean ± SD) 5. Days in hospital after ICU discharge (mean ± SD) 6. Changes of endotracheal colonisation through cultures in 3 time windows after ventilation, 1 ‐ 3 days, 5 ‐ 8 days and 9 ‐ 12 days respectively
Notes	Sample size calculation: Reported in paper together with planned sequential analysis Only Group A and Group C included in this review Email sent to author 26 August 2016 requesting mortality data but failed due to invalid email address
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"...randomly assigned to one of three study groups by computerised randomisation schedule. Randomization was stratified by hospital"
Allocation concealment (selection bias)	Low risk	The interventions were produced by an independent unit and we considered allocation was concealed from the research team.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind, placebo controlled
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Double blind, placebo controlled
Incomplete outcome data (attrition bias) All outcomes	Low risk	The study was discontinued in 6 participants, 5 participants withdrew consent, 1 due to adverse event. Intention‐to‐treat analysis included all participants for primary outcome
Selective reporting (reporting bias)	Low risk	All planned outcomes reported
Other bias	Low risk	Unlikely