Methods of Chlorhexidine Cleansing to Prevent Ventilator-Associated Pneumonia (VAP)

Patients will be assessed as follows:

CABDC ABBAA BCDDA CCCDB CACBA BBABC BAAAD DCDAC CDBAA DACDD AAACB CDBCB ACCDB BBAAD BCACC DDBCA ADCAD DABCD CBAAB DDDCD AABAB ACBCD BCCBA ADCDB CBCAB CDDCA CDDDD ABCDA ABDCB CBADD ADDBA BBCCD ABBBD DCDAC BBCCB DADBB CDBDA DBBAC AC

Adverse Events:

Adverse events that occur after endotracheal intubation, mechanical ventilation, oral cleansing with chlorhexidine, and suctioning of oropharyngeal secretions by bronchoscopy will be recorded. All adverse events including laboratory abnormalities will be recorded, even if they are thought to be unrelated to medical interventions. The severity of adverse events and any correlations with experimental drugs will be carefully recorded on the case report form.

The relationships between adverse events and drug resistance will be categorized as certainly relevant, probably relevant, possibly relevant, possibly irrelevant, or certainly irrelevant. The proportions of adverse events that are categorized as certainly relevant, probably relevant, and possibly relevant will be calculated. Severe adverse events will be recorded in a table and reported to the director of the unit and the sponsor within 24 hours.

Severity Assessment:

The severity of adverse events will be categorized as mild, moderate, or severe. A mild adverse event is defined as an event with signs and symptoms that are easy to tolerate such as nausea, vomiting, or transient localized pain. A moderate adverse event is defined as an event resulting in persistent pain. A severe adverse event is defined as an event resulting in prolonged hospitalization, disability, reduced ability to work, risk of death, or congenital malformation.

The outcomes of all adverse events will be recorded. Patients who withdraw from the trial because of adverse events will be followed up until complete resolution of the events. The investigators will judge whether the adverse events are related to the administration of experimental drugs, and will record the justification for each decision.

Data Management:

Completed case report forms will be collected by the clinical coordinator and the data will be entered into the database. After checking for accuracy, the data will be locked. After unblinding, the data will be categorized according to the four groups of patients.

Statistical Analysis:

Numerical data will be described as percentages, and measurement data as mean ± standard deviation. Abnormally distributed data will be described as median and interquartile range (25th-75th percentile).

Comparisons of Baseline Data:

Numerical data will be compared between groups using the chi-square test or Fisher's exact test. Measurement data with normal distributions will be analyzed by single- or multi-factor analysis of variance. Data with high heterogeneity will be compared using a non-parametric test such as Tamhane's T2 test. Measurement data with non-normal distributions will be compared using the non-parametric Mann-Whitney U test or the Kruskal-Wallis rank sum test. Groups will be compared at baseline and at different time points after enrollment.

Comparisons of Efficacy:

Analgesic and sedative effects will be compared among groups using the Kruskal-Wallis rank sum test. For factors showing significant differences among groups, pairwise comparisons will be analyzed using the non-parametric Mann-Whitney U test. Mean values will be compared between groups using the Cochran-Mantel-Haenszel chi-square test.

Data Processing:

All statistical analyses will be performed using SAS software. Two-sided P values will be calculated. For Fisher's exact test, the P value will be calculated directly. A value of P <0.05 is considered significant, and P <0.01 is considered highly significant.

Quality Assurance:

This study will have one principal investigator, one research investigator, and four other investigators. The clinical protocol will be strictly implemented. An independent inspector will be appointed to monitor the clinical trial.

Quality Control of the Parameters Measured:

The parameters recorded will be measured according to standard operating and quality control procedures, using standard national units of measurement. Test report forms will be fully completed including the date, parameters tested, test results, and normal ranges.

Ethical Standards:

The investigators or investigator-authorized personnel will explain the benefits and risks of participating in the clinical trial to each patient, or to the patient's legal representative. Written informed consent will be obtained prior to study entry (before performance of tests and administration of drugs). The original consent forms will be stored by the investigators.

Data Retention:

The investigators will be responsible for maintaining the database and keeping the data locked for future analysis. In accordance with the principles of good clinical practice in China, the data will be kept for at least 5 years.