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

August 4, 2026 updated by: Miguel Sanchez Garcia, Hospital San Carlos, Madrid

Prevention of Infection of the Respiratory Tract by Applying Methods That Are Non-Invasive for Extraction of Secretions. An Open Label, Randomized, Assessor-blinded Trial.

Adults who are unconscious or severely ill and need a breathing tube connected to a ventilator are at high risk of developing a lung infection (pneumonia) within the first few days in the intensive care unit. This early pneumonia affects up to 30 to 50 % of certain high-risk patients, prolongs the time on the ventilator and in hospital, and increases the use of antibiotics.

Two strategies are commonly used today to try to prevent this infection: a short, three-day course of an intravenous antibiotic, and removal of secretions from the airway with a sterile suction catheter. Both have limitations - antibiotics can favour the growth of resistant bacteria, and catheter suctioning is uncomfortable and may injure the airway.

PIRÁMIDES is a small (60-patient) pilot study that compares the current practice with two non-invasive, mechanical alternatives for keeping the airway clear: a continuous low-pressure suction system built into a special breathing tube, and a device that produces a gentle, programmed "artificial cough" through the ventilator. Adult patients who are intubated for severe trauma, severe brain injury, stroke, resuscitated cardiac arrest or other causes of decreased consciousness are randomly assigned, in equal numbers, to one of the three approaches and followed for 14 days, with a final visit at day 90.

The main goal is to find out which of the three strategies best prevents early pneumonia, and which provides the best overall result for patients when survival, severity of infection, need for additional antibiotics and side effects are considered together. To make these comparisons as fair as possible in an open-label study, an independent committee of doctors not involved in patient care reviews each suspected pneumonia case without knowing which strategy the patient received. The results will help design a larger trial to confirm which approach is safest and most effective for preventing early pneumonia in critically ill patients on a ventilator.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

PIRÁMIDES is a single-centre, open-label, randomised controlled trial (1:1:1) comparing three approved strategies for the prevention of early-onset ventilator-associated pneumonia (early VAP) in adult intubated patients at high risk of this complication (severe trauma, severe traumatic brain injury, ischaemic or haemorrhagic stroke, post-cardiac-arrest syndrome and other acute causes of decreased consciousness). Sixty patients (20 per arm) are recruited at the Critical Care Department of Hospital Clínico San Carlos (Madrid, Spain). The trial compares the standard 3-day short antibiotic course (ceftriaxone 2 g IV every 24 h) plus sterile-catheter suctioning, continuous subglottic secretion suctioning for 7 days through a dedicated endotracheal-tube channel, and 7 days of programmed sessions of a CE-marked bionic cough simulator (BCS3, Yaguo). The unit-standard topical selective digestive decontamination regimen is applied in all three arms. Intervention duration is 7 days, the main observation period extends to day 14 and final outcomes are collected at day 90. Because the interventions are visually distinct at the bedside, the trial is open-label for the treating team and patients.

The current protocol version (v2.0, April 2026) incorporates two substantial amendments. First, the objectives have been restructured: a single primary endpoint, the cumulative incidence of bacterial early VAP through day 14, replaces the original co-primary structure, and a hierarchical "Desirability of Outcome Ranking" (DOOR) endpoint at day 14 is introduced as the key secondary endpoint. The DOOR endpoint is applied identically to the three arms and integrates, in a clinically ordered five-category hierarchy, mortality, the occurrence and severity of VAP, exposure to rescue antibiotics and serious intervention-related adverse events. Categories range from (1) alive at day 14 without VAP, rescue antibiotic or related serious adverse event, to (5) death before day 14, with intermediate categories for rescue-antibiotic use without confirmed VAP, non-severe VAP, and severe VAP or major intervention-related complication.

Second, the amendment establishes an independent blinded Adjudication Committee (two intensivists specialized in ICU-acquired infections external to the trial team, one chest radiologist and one microbiologist) responsible for the final classification of every potential pneumonia episode and for the assignment of each patient to the corresponding DOOR category. The Committee reviews case-report forms, chest radiographs and lung ultrasound images, microbiology reports and other relevant clinical documentation, with all fields identifying the assigned arm removed or masked; decisions are reached by consensus.

The trial effect estimates and 95 % confidence intervals are exploratory and hypothesis-generating. The primary endpoint is analyzed in the intention-to-treat population by Fisher's exact test. The DOOR endpoint is analyzed in two pre-specified steps: a global ordinal comparison across the three arms using a proportional-odds model, followed by pairwise win-ratio comparisons on the same pre-specified hierarchy, with win odds as a sensitivity analysis and a pre-specified continuous tiebreaker (ventilator-free days through day 14, then ICU length of stay) where ties are abundant. Multiplicity between the two main pairwise comparisons (each mechanical strategy versus control) is addressed through a hierarchical testing procedure pre-specified in the Statistical Analysis Plan. A pre-specified electrical impedance tomography sub-study in five patients per arm explores the acute effects of each strategy on regional ventilation and compliance.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Belén belenhhernanz@gmail.com, PhD
  • Phone Number: +34658762739

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria

  1. Endotracheal intubation with an anticipated duration > 48 hours.

  2. High risk of early respiratory infection associated with a diagnosis of:

    1. Severe trauma.
    2. Severe traumatic brain injury.
    3. Ischaemic or haemorrhagic stroke.
    4. Other causes of impaired consciousness: post-resuscitated cardiac arrest status, intoxications, acute infections or diseases of the central nervous system, seizures.
  3. Informed consent signed by the patient or, when impossible due to clinical status, by their legal representative, with re-consent by the patients themselves upon regaining capacity (section 15).

Exclusion criteria

  1. Intubation with an anticipated duration < 48 hours.
  2. Foreseeable ominous prognosis within < 7 days.
  3. Already established indication for systemic antibiotic therapy, either for suspected aspiration pneumonia with radiological pulmonary infiltrate or for suspected non-respiratory source infection.
  4. Active haemoptysis or pulmonary haemorrhage.
  5. Unstable chest.
  6. Undrained pneumothorax (inclusion may be considered once drained).
  7. Known allergy or intolerance to beta-lactam antibiotics.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cough Simulator
Mechanical exsufflator
Device: airway clearance
mechanical suctioning of airway secretions by creating a high expiratory peak flow
Active Comparator: Standard of Care
Ceftriaxone/24 hours 3 intravenous doses
Drug: Ceftriaxone 2 grams daily
standard of care for prevention of early VAP according to Spanish recommendations (Zero Pneumonia Project)
Experimental: subglottic secretion aspiration
a specialized endotracheal tube with an aspiration channel dragging secretions accumulating above the cuff outward
Device: subglottic secretion aspiration
A specialized endotracheal tube with an aspiration channel dragging secretions accumulating above the cuff

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
Time Frame: inclusion to day 14
ventilator-associated pneumonia or tracheobronchitis
inclusion to day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Systemic antibiotic use
Time Frame: inclusion to day 14
Number of patients needing antibiotic therapy for respiratory tract infection and antimicrobial DDDs
inclusion to day 14
Incidence and type of Bacterial resistance
Time Frame: 14 days
Identification of resistance bacteria in respiratory tract samples
14 days
Desirability of Outcome Ranking
Time Frame: Outcome category asigned at Day 14
Global ordinal comparison of the five DOOR categories across the three arms
Outcome category asigned at Day 14
bacterial tracheobronchitis
Time Frame: From inclusion to day 14
Diagnostic criteria for VAP without lung infiltrate nor significant worsening of oxygenation
From inclusion to day 14
ventilator-free and respiratory-support-free days
Time Frame: From inclusion to day 14
Disconnected from ventilator and days without any respiratory support (invasive + non-invasive mechanical ventilation + high-flow nasal cannula) by day 14 of inclusion.
From inclusion to day 14
ICU and hospital length of stay
Time Frame: From inclusion to day 90
Days from admission to ICU to discharge from ICU and hospital.
From inclusion to day 90
Mortality at late follow-up
Time Frame: From inclusion to day 90
Vital status on day 90 of inclusion
From inclusion to day 90
modified Rankin score
Time Frame: Day 90
Quality of life and vital status at late follow-up day 90
Day 90
number of catheter suctioning episodes
Time Frame: From inclusion to day 7
Sterile catheter suctioning needs in all study arms
From inclusion to day 7
Antimicrobial exposure endpoints: antibiotic-free days, use of rescue antibiotics, isolation of clinically relevant resistant organisms on day 14.
Time Frame: From inclusion to day 14
Ecological impact assessment
From inclusion to day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital San Carlos, Madrid

Collaborators

SAMUR-Protección Civil, Madrid, Spain

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 15, 2026

Primary Completion (Estimated)

December 30, 2028

Study Completion (Estimated)

June 30, 2029

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)

August 6, 2026

Last Update Submitted That Met QC Criteria

August 4, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PIRAMIDES
  • 2025-521454-42-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Upon presentation of an analysis plan and local approvement by ERB.

IPD Sharing Time Frame

From publication of study onwards. No time limit.

IPD Sharing Access Criteria

Contact with central contact person or principal investigator.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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