Stefanescu 2013.

Study characteristics
Methods	Study design: 2‐arm parallel‐group RCT Location: USA Number of centres: 1 Study period: June 2010 to January 2012 Funding source: Forsyth Medical Center Sara Lee for Women’s Health and WFSM Department of Paediatric Research Funds
Participants	Setting: neonatal ICU Inclusion criteria: extremely low birth weight, gestational age ≤ 28 weeks, receipt of mechanical ventilation of at least 3 days in the first week of life and in the interval between days 7 and 10 of life; a parent provided written informed consent Exclusion criteria: chromosomal or major congenital anomaly, the attending physician did not intend to provide full medical support Number randomised: 41 (biotene: 20; control: 21) Number evaluated: 41 (biotene: 20; control: 21) Baseline characteristics: ‐ Biotene: (median gestational age: 24 weeks (24‐25); M/F: 7/13) ‐ Control: (median gestational age: 25 weeks (24‐25); M/F: 11/10)
Interventions	Comparison: biotene vs control Biotene: timed oral care performed using sterile foam‐tip swabs with OralBalance Gel from 2 mL single use twist‐tip vials, and involved hygiene of buccal mucosa, tongue and areas around endotracheal tube, every 4 hours from enrolment to final extubation. Control: timed oral care performed using sterile foam tip swabs with sterile water from 2 mL single use twist‐tip vials, and involved hygiene of buccal mucosa, tongue and areas around endotracheal tube, every 4 hours from enrolment to final extubation. All infants received VAP bundling, consisting of good hand hygiene and use of gloves when handling respiratory secretions, head of bed elevation, avoidance of routine use of saline with tracheal suctioning process, and weekly change of ventilator circuits.
Outcomes	1. Incidence of VAP 2. Number of VAP per 1000 ventilator days 3. Mortality 4. Length of hospital stay 5. Duration of mechanical ventilation 6. Micro‐organism colonisation in tracheal aspirate 7. Adverse effects
Notes	Sample size calculation: not reported; a pilot study
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	“We used blocked randomisation with varying block size”. Probably done using computer‐generated random numbers
Allocation concealment (selection bias)	Low risk	“Group assignments were provided in sealed envelopes which were kept secure by the investigational pharmacist, who was responsible for identifying the group to which each randomised patient was allocated”.
Blinding of participants and personnel (performance bias) All outcomes	High risk	“the primary limitation to our study was that we did not blind the staff to the intervention”.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	"All radiographs where VAP was suspected were reviewed with the paediatric radiologists who were blinded to individual study assignment”. Potential for bias in deciding whether VAP was suspected
Incomplete outcome data (attrition bias) All outcomes	Low risk	No dropouts
Selective reporting (reporting bias)	Low risk	Planned outcomes reported
Other bias	Unclear risk	More infants in the control group received a complete course of antenatal steroids compared to infants in the biotene group (P = 0.045). A complete course of antenatal steroids improves neonatal lung maturity and function and may reduce the risk of VAP (Roberts 2017). This imbalance is likely to lead to an underestimate of the benefit of the active treatment.