Scannapieco 2009.
| Methods | Study design: A randomised, double‐blind, placebo‐controlled clinical trial Location: USA Number of centres: 1 18‐bed trauma ICU Study period: March 2004 until November 2007 Funding source: USPH grant R01DE‐14685 from the National Institute of Dental and Craniofacial Research |
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| Participants | Inclusion criteria: Those admitted to the ICU who were expected to be intubated and mechanically ventilated within 48 hours of admission Exclusion criteria: A witnessed aspiration suspected with chemical pneumonitis; a confirmed diagnosis of post‐obstructive pneumonia e.g. advanced lung cancer; a known hypersensitivity to chlorhexidine; absence of consent; a diagnosed thrombocytopenia (platelet count < 40 and/or a INR > 2, or other coagulopathy); a do‐not‐intubate order; children < 18 years; pregnant women; legal incarceration; transfer from another ICU; oral mucositis; immunosuppression either HIV‐ or drug‐induced e.g. organ transplant patients or those on long‐term steroid therapy; and readmission to the ICU Number randomised: 175 Number evaluated: 146 Intervention group (chlorhexidine 1): n = 47; mean age: 44.8 ± 19.9; M/F: 43/15; mean APACHE II Score: 18.5 ± 4.1 Intervention group (chlorhexidine 2): n = 50; mean age: 47.6 ± 19.1; M/F: 44/14; mean APACHE II Score: 19.7 ± 6.1 Control group: n = 49; mean age: 50.0 ± 22.5; M/F: 36/23; mean APACHE II Score: 19.1 ± 6.1 |
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| Interventions |
Comparison: Chlorhexidine twice per day + toothbrush versus chlorhexidine once per day + toothbrush versus placebo + toothbrush Intervention group: Chlorhexidine (0.12% CHX gluconate) was applied using a rinse‐saturated oral foam applicator (Sage Products, Cary, IL, USA) once a day (placebo at other time) Intervention group: Chlorhexidine (0.12% CHX gluconate) was applied using a rinse‐saturated oral foam applicator (Sage Products, Cary, IL, USA) twice a day (in the morning at about 8 AM and in the evening at about 8 PM) Control group: Placebo was applied using a rinse‐saturated oral foam applicator twice per day All groups had routine oral care using a suction toothbrush (Sage Products, Cary, IL, USA) twice a day and as needed to brush teeth and the surface of the tongue or approximately 1 ‐ 2 minutes, and applying suction at completion and as needed during the brushing |
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| Outcomes | 1. Incidence of VAP (diagnosed as the presence of more than 104 CFU of pathogen/ml of bqBAL fluid) 2. Death 3. Days ventilated 4. Days in hospital 5. Antibiotic use |
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| Notes | Sample size calculation: Estimated that 53 participants per arm would give 90% power to detect a 505 decrease in colonisation. For outcomes 2 ‐ 5, the P values were for 3‐group comparisons NCT00123123 at ClinicalTrials.gov |
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| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | A web‐based enrolment system which allocated randomised participant identification numbers |
| Allocation concealment (selection bias) | Low risk | The oral topical treatment for each box was formulated and prepared by the hospital pharmacy. Sealed envelopes containing a random number were generated in blocks of 6 to provide concealment of participant assignment from the investigators |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | "Assignment of treatment was blinded to patients and all investigators including outcome assessors, statisticians and care providers" |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | "Assignment of treatment was blinded to patients and all investigators including outcome assessors, statisticians and care providers" |
| Incomplete outcome data (attrition bias) All outcomes | High risk | 175 participants were randomised, microbiological baseline data were available for 146 participants, 115 had full data at 48 hours. > 20% dropouts in all groups. ITT analysis used for 175 participants but unclear what imputation was used to account for losses |
| Selective reporting (reporting bias) | Unclear risk | Planned microbiological outcomes were reported only in graphs with no data presented |
| Other bias | High risk | Problems with data analysis due to unclear denominator and imputations. Pre‐study antibiotic exposure higher in control group |