The Effect of Prone Position Drainage on the Efficacy of Severe Pneumonia，a Multicenter Randomized Controlled Trial

Enrollment criteria and clinical data collection: follow the principles of medical ethics, the development of inclusion and exclusion criteria, Select all eligible patients with severe pneumonia(SP) who were admitted to the hospital during the study date.The diagnostic criteria we will use for SP are based on the Infectious Diseases Society of America/American Thoracic Society guidelines.Primary outcome measures：a.CURB-65 Score for Pneumonia Severity;b.The changes in inflammation and coagulation indicators: C-reactive protein, procalcitonin, and d-dimer;c.Chest x-ray changes;d.Mortality rate after 28 days;e.The time of mechanical ventilation, total duration of ICU stay, hospitalization, and antibiotic use;f.The time of bacterial cultures becoming negative;g.Daily sputum drainage.The aim of this study is to evaluate the anti-infective effectiveness and safety of prone position drainage compared with supine position on SP treatment.

Study Overview

• Status: Unknown
• Conditions: Severe Pneumonia
• Intervention / Treatment: Behavioral: Placed in prone position for at least 16 consecutive hours a day.

Detailed Description

Severe pneumonia (SP) is a major complication of respiratory system diseases that is associated with high mortality and morbidity. If not treated correctly, it may rapidly lead to sepsis and multiple organ dysfunction syndrome. Randomized, controlled trials have confirmed that oxygenation is significantly better when patients are in the prone position than when they are in the supine position.But whether prone drainage is beneficial for rapid infection control on SP treatment has not been researched.The aim of this study is to evaluate the anti-infective effectiveness and safety of prone position drainage compared with supine position on SP treatment.

Using a central randomization system, participants will be randomized (1:1) into groups receiving either placed in prone position or in supine position (within 24 h of diagnosis of SP) for 5-7 days with a 28-day follow-up. Patients assigned to the prone group had to be turned within the first hour following randomization. They were placed in prone position for at least 16 consecutive hours.

The patients enrolled in this study should meet the diagnostic and inclusion criteria and provide written informed consent.

Diagnostic criteria The diagnostic criteria we will use for SP are based on the Infectious Diseases Society of America/American Thoracic Society guidelines.

The inclusion criteria are as follows:

1.Age ≥18 years and ≤75 years, male or female；2.Weight ≥40 kg and ≤100 kg；3.Meet the diagnostic criteria for SP；4.Need invasive mechanical ventilation；5.Provide signed informed consent

Non-inclusion criteria:

1. Contraindication for prone positioning

   a. Intracranial pressure >30 mm Hg or cerebral perfusion pressure <60 mmHg;b. Massive hemoptysis requiring an immediate surgical or interventional radiology procedure; c. Tracheal surgery or sternotomy during the previous 15 days;d. Serious facial trauma or facial surgery during the previous 15 days;e. Deep venous thrombosis treated for less than 2 days; f. Cardiac pacemaker inserted in the last 2 days;g. Unstable spine, femur, or pelvic fractures;h. Mean arterial pressure lower than 65 mm Hg;i. Pregnant women; j. Single anterior chest tube with air leaks.

2. Respiratory reason

   1. Inhaled nitric oxide (NOi) or almitrine bismesylate use before inclusion;b. Use of extracorporeal membrane oxygenation (ECMO) before inclusion.
3. Clinical context a. Lung transplantation;b. Burns on more than 20 % of the body surface;c. Chronic respiratory failure requiring oxygen therapy or non-invasive ventilation(NIV);d. Underlying disease with a life expectancy of less than one year;e. NIV delivered for more than 24 hours before inclusion.
4. Other non-inclusion criteria a. End-of-life decision before inclusion;b. Inclusion in another research protocol in the previous 30 days with mortality as the main end-point;c. Prone positioning before inclusion;d. Subject deprived of freedom, minor, subject under a legal protective measure;e. Opposition from next of kin.

Suspension criteria

The criteria for suspension of participation are as follows:

1.Poor compliance of investigators or patients;2.Occurrence of serious adverse events (AEs), complications, or fatal physiological changes;3.Voluntary withdrawal;4.Incomplete data; Primary outcome measures：

a.CURB-65 Score for Pneumonia Severity;b.The changes in inflammation and coagulation indicators: C-reactive protein, procalcitonin, and d-dimer;c.Chest x-ray changes;d.Mortality rate after 28 days;e.The time of mechanical ventilation, total duration of ICU stay, hospitalization, and antibiotic use;f.The time of bacterial cultures becoming negative;g.Daily sputum drainage.

The statistical analysis will be performed using SAS software version 9.4 (SAS Institute, Cary, NC, USA). If the lower limit of the 95 % confidence interval is larger than a clinically meaningful difference, therapeutic effects of the experimental group are deemed to be clinically and statistically better than those of the control group. Two-sided tests will be performed for all the other statistical analyses. Cochran-Mantel-Haenszel χ2 tests or Fisher's exact tests will be used for comparison of categorical outcomes. Continuous outcomes will be analyzed by using Student's t test. p values ˂0.05 are considered to indicate statistical significance.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years and ≤75 years, male or female
• Weight ≥40 kg and ≤100 kg
• Meet the diagnostic criteria for SP
• Need invasive mechanical ventilation
• Provide signed informed consent

Exclusion Criteria:

• Contraindication for prone positioning：a. Intracranial pressure >30 mm Hg or cerebral perfusion pressure <60 mmHg;b. Massive hemoptysis requiring an immediate surgical or interventional radiology procedure; c. Tracheal surgery or sternotomy during the previous 15 days;d. Serious facial trauma or facial surgery during the previous 15 days;e. Deep venous thrombosis treated for less than 2 days; f. Cardiac pacemaker inserted in the last 2 days;g. Unstable spine, femur, or pelvic fractures;h. Mean arterial pressure lower than 65 mm Hg;i. Pregnant women; j. Single anterior chest tube with air leaks.
• Respiratory reason：a. Inhaled nitric oxide (NOi) or almitrine bismesylate use before inclusion;b. Use of extracorporeal membrane oxygenation (ECMO) before inclusion.
• Clinical context：a. Lung transplantation;b. Burns on more than 20 % of the body surface;c. Chronic respiratory failure requiring oxygen therapy or non-invasive ventilation(NIV);d. Underlying disease with a life expectancy of less than one year;e. NIV delivered for more than 24 hours before inclusion.
• Other non-inclusion criteria ：a. End-of-life decision before inclusion;b. Inclusion in another research protocol in the previous 30 days with mortality as the main end-point;c. Prone positioning before inclusion;d. Subject deprived of freedom, minor, subject under a legal protective measure;e. Opposition from next of kin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: The prone group; Patients assigned to the prone group had to be turned within the first hour following randomization. They were placed in prone position for at least 16 consecutive hours.	Behavioral: Placed in prone position for at least 16 consecutive hours a day.; Patients assigned to the prone group had to be turned within the first hour following randomization. They were placed in prone position for at least 16 consecutive hours. Patients assigned to the control group had to be turned within the first hour following randomization. They were placed in supine position for at least 16 consecutive hours.
No Intervention: The supine group; Patients assigned to the supine group had to be turned within the first hour following randomization. They were placed in supine position for at least 16 consecutive hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The changes in C-reactive protein	Use C-reactive protein to assess the patient's lung infection status	On the tenth day after hospitalization
The changes in procalcitonin	Use procalcitonin to assess the patient's lung infection status	On the tenth day after hospitalization
The changes in d-dimer	Use d-dimer to assess the patient's lung infection status	On the tenth day after hospitalization
Chest x-ray changes	Use Chest x-ray to assess the patient's lung infection status	On the tenth day after hospitalization
Mortality rate after 28 days	Calculate patient 28-day mortality	28 days after admission
The time of total duration of ICU stay	Calculate The time of total duration of ICU stay	28 day
The time of mechanical ventilation	Calculate The time of mechanical ventilation	28 day
mortality	Using the Kaplan-Meier method to analyze the differences in mortality between the two groups within 28 days	28 day
The time of antibiotic use	Calculate the time of antibiotic use	28 day
The time of bacterial cultures becoming negative	Calculate the time of bacterial cultures becoming negative	28 day
Daily sputum drainage	Calculate daily sputum drainage	On the tenth day after hospitalization

Collaborators and Investigators

• Sponsor: Xiangya Hospital of Central South University
• Collaborators: National Natural Science Foundation of China
• Investigators: Study Director: Pinhua Pan, Doctor, Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): April 1, 2022

Study Registration Dates

• First Submitted: March 18, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 25, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Prone Position; Treatment Outcome; Respiration, Artificial
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia
• Other Study ID Numbers: 81770081

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No