Prevention of Infection of the Respiratory Tract Through Application of Non-Invasive Methods of Secretion Suctioning (PIRAMIDES)

A Randomized Controlled Pilot Trial Comparing 2 Non-invasive Airway Clearance Methods for the Prevention of Early-onset Ventilator-associated Pneumonia.

Severe trauma, head trauma, stroke and resuscitated cardiac arrest patients requiring endotracheal intubation and mechanical ventilation are at high risk of early-onset ventilator-associated pneumonia (EO-VAP). A short course of systemic antibiotic is recommended for prophylaxis.

This study intends to assess the safety and efficacy of 2 alternative mechanical non-invasive airway clearance techniques in the prevention of EO-VAP in an open label randomized pilot trial of 20 subjects per study group i.e., 60 cases. The interventions will be in place for 7 days and the observational periods will be 14 days.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiac Arrest; Stroke, Ischemic; Stroke Hemorrhagic; Ventilator Associated Pneumonia; Intubation Complication; Head Trauma; Airway Clearance Impairment
• Intervention / Treatment: Device: airway clearance

Detailed Description

Background. Patients with structural coma are at high risk of so-called early onset pneumonia (EOP). Incidence rates of up to 50% have been reported in patients with head trauma or stroke. The usual causative microorganisms belong to the normal upper airway flora like Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenza and Moraxella catarrhalis. EOP typically is not present at admission and develops after 2 to 7 days after endotracheal intubation.

A short course of systemic antibiotic therapy and aspiration of subglottic secretions (ASS) are associated with significant reductions in EOP, although ASS does not prevent late-onset pneumonia. Non-invasive mechanical methods may avoid the use of prophylactic antibiotics and pain and injury to the tracheal mucosa caused by the conventional suctioning catheter.

The primary objectives of the present randomized pilot trial is to compare the prevention of respiratory tract infections during invasive mechanical ventilation and occurrence of device-associated adverse events of non-invasive mechanical airway clearance devices with standard of care in the ICU Department at Hospital Clinico San Carlos.

Secondary objectives are duration of intubation and respiratory support (mechanical intubation plus high flow nasal cannula).

Methods. Informed consent will be requested from relatives in patients admitted to intensive care (Neuro-trauma unit) requiring endotracheal intubation estimated to last >48 hours, who do not have a hopeless prognosis.

Closed envelopes will be used for allocation to one of the 3 study groups::

1. Control group: ceftriaxone 2 g/24 hours, 3 doses
2. Subglottic aspiration of secretions
3. Cough simulator

Patients in all groups will receive the topical components of selective decontamination of the digestive tract (SDD) while intubated.

In groups 2 and 3 the allocated study group prevention intervention will be applied during the first 7 days.

The main study objectives will be monitored over the first 14 days of intubation or until extubation if performed before day 14.

Sample size will be 60 subjects, 20 per study group, enrolled in blocs of 5, with the 5th case of each bloc being allocated in random sequence.

Nurses will be trained in using the devices for groups 2 and 3 before the start of enrollment phase.

The diagnosis of pneumonia vs tracheobronchitis will be based on chest x-ray and confirmed by lung ultrasound to exclude chest x-ray false negatives.

On day 5 to 7 or immediately before extubation, if planned earlier, electrical impedance tomography will be performed to compare lung air distribution and compliance between groups.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Miguel Sánchez Garcia, MD. PhD.; Phone Number: +34658762739; Email: miguelsanchez.hcsc@gmail.com
• Study Contact Backup: Name: Belén belenhhernanz@gmail.com, PhD; Phone Number: +34658762739

Study Locations

• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Endotracheal intubation anticipated to last >48 hours
• Stroke
• Severe Trauma
• Head Trauma
• Resuscitated cardiac arrest

Exclusion Criteria:

• Ominous prognosis
• Limitation of Life support

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care; IV ceftriaxone/24 hours 3 doses	Device: airway clearance; mechanical suctioning of airway secretions
Experimental: Subglottic aspiration; Continuos aspiration of subglottic secretions	Device: airway clearance; mechanical suctioning of airway secretions
Experimental: Cough Simulator; Mechanical exsufflator	Device: airway clearance; mechanical suctioning of airway secretions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence density of Respiratory tract infection per 1000 days of intubation	ventilator-associated pneumonia or tracheobronchitis	inclusion to day 14
Incidence of adverse events	Device-related complications	inclusion to day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Respiratory support	Duration of mechanical ventilation plus high-flow nasal cannula	inclusion until ICU discharge or death
Systemic antibiotic use	Number of patients needing antibiotic therapy for respiratory tract infection and antimicrobial DDDs	inclusion to day 14
Incidence and type of Bacterial resistance	Identification of resistance bacteria in respiratory tract samples	14 days

Collaborators and Investigators

• Sponsor: Hospital San Carlos, Madrid
• Investigators: Study Director: Manuel Alvarez-Gonzalez, MD.PhD, Hospial Clinico San Carlos; Principal Investigator: Sandra Garcia Pintado, RN, Hospial Clinico San Carlos

Study record dates

Study Major Dates

• Study Start (Estimated): May 19, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 20, 2026

Study Registration Dates

• First Submitted: October 10, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: prevention; ventilator-associated pneumonia; airway clearance
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Trauma, Nervous System; Cross Infection; Iatrogenic Disease; Ischemic Stroke; Hemorrhagic Stroke; Stroke; Pneumonia; Pneumonia, Ventilator-Associated; Craniocerebral Trauma
• Other Study ID Numbers: PIRAMIDES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No