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.

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.