Seguin 2014.

Methods	Study design: 2‐arm parallel group RCT Location: France Number of centres: 6 Study period: May 2008 to May 2011 Funding source: French Ministry of Health
Participants	Setting: ICU Inclusion criteria: > 18 years, closed traumatic brain injury (Glasgow Coma Score ≤ 8), expected mechanical ventilation ≥ 48 hours. Protocol amended to include patients with cerebral haemorrhage. Exclusion criteria: patients in whom oral care procedure could not be performed within 12 hours after intubation, or had tetraplegia, facial trauma, pulmonary contusion involving > 1 lobe, aspiration pneumonia, current curative antimicrobial therapy, known allergy to povidone‐iodine, pregnancy. Number randomised: 179 (Povidone‐Iodine: 91; Control: 88) Number evaluated: 150 (Povidone‐Iodine: 78; Control: 72) Baseline characteristics: ‐ Povidone Iodine*: Age: 48 (19); M/F: 60/25; SAPS II Score: 47 (11) ‐ Control*: Age: 48 (18); M/F: 64/18; SAPS II Score: 46 (12) * data presented on participants analysed
Interventions	Comparison: Povidone‐Iodineversus Placebo Povidone Iodine: Betadine 10% oral antiseptic solution portioned in identical vials containing 125 mL of product. Participants received nasopharynx and oropharynx rinsing with 20 mL of povidone iodine (10%) using a 60 mL syringe (final concentration 3.3%). The solution was progressively injected in the buccal and pharyngeal cavities and regularly suctioned during 2 minutes, every 4 hours. The protocol was continued until extubation or until day 30. Placebo: used as above.
Outcomes	1. Incidence of VAP 2. VAP as time to first occurrence 3. Incidence of early (< 7 days) and late (≥ 7 days) VAP 4. Incidence density of VAP per 1000 ventilator days 5. ICU and 90‐day mortality 6. Duration of ICU and hospital stay 7. Number of ventilation‐free days 8. Oropharayngeal and tracheal colonisation by potentially pathogenic microorganisms 9. Incidence of ventilator‐associated tracheobronchitis 10. Incidence of acute respiratory distress syndrome 11. Events of other nosocomial infections 12. Systemic antibiotic use 13. Adverse effects: agitation/hypertension, epistaxis, oxygen desaturation, aspiration, others
Notes	Sample size calculation: reported for VAP
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“Randomization was centralized and performed by the pharmacy of the coordinating centre, stratified by centre and by type of patients (trauma or cerebral haemorrhage), and equilibrated by blocks of 4”. Probably done well using computer‐generated random numbers
Allocation concealment (selection bias)	Low risk	“Randomization was centralized and performed by the pharmacy of the coordinating centre, stratified by centre and by type of patients (trauma or cerebral haemorrhage), and equilibrated by blocks of 4”.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	“The placebo was identical to povidone‐iodine in terms of colour, small and texture. Both povidone‐iodine and placebo were portioned in identical vials”
Blinding of outcome assessment (detection bias) All outcomes	Low risk	“An independent diagnosis validation committee. . blindly classified each patient as positive or negative for VAP.”
Incomplete outcome data (attrition bias) All outcomes	Low risk	16% attrition rate for VAP incidence but the numbers and reasons for lost to follow‐up were similar in each group.
Selective reporting (reporting bias)	Low risk	Planned outcomes reported.
Other bias	Low risk	No other sources of bias identified