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

NCT ID: NCT02077920

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 192 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2019-08-31

Brief Summary

Ventilator-associated pneumonia (VAP) is common in patients receiving mechanical ventilation, and is associated with longer hospital stay, increased treatment costs, and higher rates of morbidity and mortality . VAP is reported to occur in 8%-67% of mechanically ventilated patients (20%-28% in most reports) and has a mortality rate of 24%-50%, which is 2-3 times the mortality rate of mechanically ventilated patients without VAP. In patients infected by multi-resistant bacteria, the mortality rate may be as high as 76%. The diagnosis, treatment, and prevention of VAP are therefore important. Strategies for preventing VAP are crucial for reducing medical costs and increasing survival rates in critically ill patients. These strategies mainly involve a semi-reclining position with the head of the bed raised to at least 30°-45°, oral care, suctioning of subglottic secretions, selective decontamination of the digestive tract, proper hand washing, avoidance or reduction of proton pump inhibitors, avoidance of excessive sedation, and control of plasma glucose levels.

At our center, VAP is mainly caused by bacterial colonization of the upper respiratory tract via aspiration. This study will compare four interventions including oropharyngeal decontamination and subglottic suctioning by bronchoscopy, with the aim of developing a prevention strategy to minimize the development of VAP during mechanical ventilation.

Detailed Description

Patients will be assessed as follows:

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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.

Conditions

Ventilator-associated Pneumonia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Chlorhexidine before intubation

Group A: Oropharyngeal decontamination with chlorhexidine before intubation, n=48. Oral cleansing with chlorhexidine will be performed before endotracheal intubation, and every 6 hours after intubation.

Group Type: EXPERIMENTAL

Chlorhexidine

Intervention Type: DRUG

SFDA Approval No. H21020748; Jinzhou Jiu Tai Pharmaceutical Co., Ltd., Liaoning, China

Drug administration and preparation:

• Drug administration: oropharyngeal rinsing and suctioning of subglottic secretions
• Drug preparation: 0.12% chlorhexidine solution prepared with distilled water that has been sterilized by autoclaving

Endotracheal tube

Intervention Type: DEVICE

Type 5-10115; size 7.0 mm, 7.5 mm, or 8.0 mm; purchased from Teleflex Medical (USA).

Chlorhexidine after intubation

Group B: Oropharyngeal decontamination with chlorhexidine after intubation, n=48. Oral cleansing with chlorhexidine will be performed every 6 hours after endotracheal intubation.

Group Type: EXPERIMENTAL

Chlorhexidine

Intervention Type: DRUG

SFDA Approval No. H21020748; Jinzhou Jiu Tai Pharmaceutical Co., Ltd., Liaoning, China

Drug administration and preparation:

• Drug administration: oropharyngeal rinsing and suctioning of subglottic secretions
• Drug preparation: 0.12% chlorhexidine solution prepared with distilled water that has been sterilized by autoclaving

Endotracheal tube

Intervention Type: DEVICE

Type 5-10115; size 7.0 mm, 7.5 mm, or 8.0 mm; purchased from Teleflex Medical (USA).

Subglottic secretion drainage

Group C: Suctioning of subglottic secretions, n=48. Oral cleansing with chlorhexidine will be performed before endotracheal intubation and every 6 hours after intubation, and fiberoptic bronchoscopy-guided suctioning of subglottic secretions will be performed at 10:00 a.m. every day. The procedure will be as follows:

1. Routine cleaning of the bronchoscope.

2. Oral or nasal insertion of the bronchoscope (according to the decision of the attending physician based on the patient's condition). Rinsing of the subglottic region with 5-20 mL of chlorhexidine solution followed by suctioning. The rinsing procedure will be repeated 3-5 times.

3. Routine cleaning of the bronchoscope. The patient will be monitored during all procedures.

Group Type: EXPERIMENTAL

Chlorhexidine

Intervention Type: DRUG

SFDA Approval No. H21020748; Jinzhou Jiu Tai Pharmaceutical Co., Ltd., Liaoning, China

Drug administration and preparation:

• Drug administration: oropharyngeal rinsing and suctioning of subglottic secretions
• Drug preparation: 0.12% chlorhexidine solution prepared with distilled water that has been sterilized by autoclaving

Fiber bronchoscope

Intervention Type: DEVICE

For suctioning of subglottic secretions. BF-P30 (Olympus, Japan); BF-1T20 (Olympus, Japan); or FB-18BS (Pentax, Japan).

0.9% sodium chloride injection

Group D: 0.9% sodium chloride injection, n=48. After endotracheal intubation, oral cleansing with normal saline will be performed every 6 hours.

Group Type: EXPERIMENTAL

0.9% sodium chloride injection

Intervention Type: DRUG

SFDA Approval No. H20045252; Shenyang Zhiying Pharmaceutical Co., Ltd., Liaoning, China

Endotracheal tube

Intervention Type: DEVICE

Type 5-10115; size 7.0 mm, 7.5 mm, or 8.0 mm; purchased from Teleflex Medical (USA).

Interventions

Chlorhexidine

SFDA Approval No. H21020748; Jinzhou Jiu Tai Pharmaceutical Co., Ltd., Liaoning, China

Drug administration and preparation:

• Drug administration: oropharyngeal rinsing and suctioning of subglottic secretions
• Drug preparation: 0.12% chlorhexidine solution prepared with distilled water that has been sterilized by autoclaving

Intervention Type: DRUG

0.9% sodium chloride injection

SFDA Approval No. H20045252; Shenyang Zhiying Pharmaceutical Co., Ltd., Liaoning, China

Intervention Type: DRUG

Endotracheal tube

Type 5-10115; size 7.0 mm, 7.5 mm, or 8.0 mm; purchased from Teleflex Medical (USA).

Intervention Type: DEVICE

Fiber bronchoscope

For suctioning of subglottic secretions. BF-P30 (Olympus, Japan); BF-1T20 (Olympus, Japan); or FB-18BS (Pentax, Japan).

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients who are scheduled for endotracheal intubation and mechanical ventilation.

Exclusion Criteria

• Patients who underwent endotracheal intubation or tracheotomy before study enrollment.
• Patients who underwent endotracheal intubation and mechanical ventilation within 30 days before study enrollment.
• Patients who require cardiopulmonary resuscitation.
• Patients with a history of emesis and aspiration before endotracheal intubation.
• Patients who are judged unsuitable for enrollment by clinicians.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

General Hospital of Shenyang Military Region

OTHER

Sponsor Role: lead

Responsible Party

Zhuang Ma

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Zhuang Ma, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The General Hospital of Shenyang Military Region

Locations

The General Hospital of Shenyang Military Region

Shenyang, Liaoning, China

Countries

China

Other Identifiers

GHS-RCU-001

Identifier Type: -

Identifier Source: org_study_id