Intubation ComplicationPhase 4PIRAMIDESNCT06113939
Prevention of Infection of the Respiratory Tract Through Application of Non-Invasive Methods of Secretion Suctioning
A Phase 4 study testing airway clearance, subglottic secretion aspiration and Ceftriaxone 2 grams daily in people with Intubation Complication and Stroke, Ischemic, run by Hospital San Carlos, Madrid at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intubation Complication, Stroke, Ischemic, Stroke Hemorrhagic
- What is being tested?
- airway clearance, subglottic secretion aspiration and Ceftriaxone 2 grams daily
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteSpain
- Study dates
- 15 Sep 2026to 30 Jun 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Endotracheal intubation with an anticipated duration > 48 hours.
- High risk of early respiratory infection associated with a diagnosis of:
- Severe trauma.
- Severe traumatic brain injury.
- Ischaemic or haemorrhagic stroke.
- Other causes of impaired consciousness: post-resuscitated cardiac arrest status, intoxications, acute infections or diseases of the central nervous system, seizures.
- 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).
Who cannot join
- Intubation with an anticipated duration < 48 hours.
- Foreseeable ominous prognosis within < 7 days.
- Already established indication for systemic antibiotic therapy, either for suspected aspiration pneumonia with radiological pulmonary infiltrate or for suspected non-respiratory source infection.
- Active haemoptysis or pulmonary haemorrhage.
- Unstable chest.
- Undrained pneumothorax (inclusion may be considered once drained).
- Known allergy or intolerance to beta-lactam antibiotics.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belén belenhhernanz@gmail.com, PhD contact
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Intubation Complication, Stroke, Ischemic, Stroke Hemorrhagic, Head Trauma, Cardiac Arrest, Ventilator Associated Pneumonia
- Being tested
- airway clearance, subglottic secretion aspiration, Ceftriaxone 2 grams daily
- Keywords
- ventilator-associated pneumonia, prevention, airway clearance
- Medical subject headings
- Ischemic Stroke, Hemorrhagic Stroke, Craniocerebral Trauma, Heart Arrest, Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
airway clearanceDevice
mechanical suctioning of airway secretions by creating a high expiratory peak flow
subglottic secretion aspirationDevice
A specialized endotracheal tube with an aspiration channel dragging secretions accumulating above the cuff
Ceftriaxone 2 grams dailyDrug
standard of care for prevention of early VAP according to Spanish recommendations (Zero Pneumonia Project)
| Study group | Role | What they receive |
|---|---|---|
| Standard of Care | Active comparator | Ceftriaxone/24 hours 3 intravenous doses Receives: Drug: Ceftriaxone 2 grams daily |
| Cough Simulator | Experimental | Mechanical exsufflator Receives: Device: airway clearance |
| subglottic secretion aspiration | Experimental | a specialized endotracheal tube with an aspiration channel dragging secretions accumulating above the cuff outward Receives: Device: subglottic secretion aspiration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence density of Respiratory tract infection per 1000 days of intubation
ventilator-associated pneumonia or tracheobronchitis
Measured: inclusion to day 14
Secondary outcomes (10)
Desirability of Outcome Ranking
Global ordinal comparison of the five DOOR categories across the three arms
Measured: Outcome category asigned at Day 14
Systemic antibiotic use
Number of patients needing antibiotic therapy for respiratory tract infection and antimicrobial DDDs
Measured: inclusion to day 14
Incidence and type of Bacterial resistance
Identification of resistance bacteria in respiratory tract samples
Measured: 14 days
bacterial tracheobronchitis
Diagnostic criteria for VAP without lung infiltrate nor significant worsening of oxygenation
Measured: From inclusion to day 14
ventilator-free and respiratory-support-free days
Disconnected from ventilator and days without any respiratory support (invasive + non-invasive mechanical ventilation + high-flow nasal cannula) by day 14 of inclusion.
Measured: From inclusion to day 14
ICU and hospital length of stay
Days from admission to ICU to discharge from ICU and hospital.
Measured: From inclusion to day 90
Mortality at late follow-up
Vital status on day 90 of inclusion
Measured: From inclusion to day 90
modified Rankin score
Quality of life and vital status at late follow-up day 90
Measured: Day 90
number of catheter suctioning episodes
Sterile catheter suctioning needs in all study arms
Measured: From inclusion to day 7
Antimicrobial exposure endpoints: antibiotic-free days, use of rescue antibiotics, isolation of clinically relevant resistant organisms on day 14.
Ecological impact assessment
Measured: From inclusion to day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2023
- Study start15 Sep 2026 (estimated)
- Primary completion30 Dec 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Intubation ComplicationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open label, randomized, assessor-blinded (evaluation committee unaware of study group allocation)
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital San Carlos, Madrid
- Sponsor type
- University, hospital or other
- Collaborators
- SAMUR-Protección Civil, Madrid, Spain
- Responsible party
- Principal investigator, Miguel Sanchez Garcia, Hospital San Carlos, Madrid
- Investigators
- Manuel Alvarez-Gonzalez, MD.PhD, Study director, Hospial Clinico San CarlosSandra Garcia Pintado, RN, Principal investigator, Hospial Clinico San Carlos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06113939
- Sponsor's protocol ID
- PIRAMIDES
- Other IDs
- 2025-521454-42-00, 2025
- Acronym
- PIRAMIDES
- Status last verified
- Aug 2026
- First submitted
- 10 Oct 2023
- Last updated
- 6 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon presentation of an analysis plan and local approvement by ERB.
Publications
van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988 May;19(5):604-7. doi: 10.1161/01.str.19.5.604.
PubMed 3363593Ranzani OT, Singer M, Salluh JIF, Shankar-Hari M, Pilcher D, Berger-Estilita J, Coopersmith CM, Juffermans NP, Laffey J, Reinikainen M, Neto AS, Tavares M, Timsit JF, Arias Lopez MDP, Arulkumaran N, Aryal D, Azoulay E, Celi LA, Chaudhuri D, De Lange D, De Waele J, Dos Santos CC, Du B, Einav S, Engelbrecht T, Fazla F, Ferrer R, Finazzi S, Fujii T, Gershengorn HB, Greene JD, Haniffa R, Hao S, Hasan MS, Hollenberg S, Ippolito M, Jung C, Kirov M, Kobari S, Lakbar I, Lipman J, Liu V, Liu X, Lobo SM, Magatti D, Martin GS, Metnitz B, Metnitz P, Myatra SN, Oczkowski S, Paiva JA, Paruk F, Pekkarinen PT, Piquilloud L, Polkki A, Prescott HC, Blaser AR, Rezende E, Robba C, Rochwerg B, Ruckly S, Samei R, Schenck EJ, Secombe P, Sendagire C, Siaw-Frimpong M, Simpkin AJ, Soares M, Summers C, Szczeklik W, Takala J, Tanaka S, Tricella G, Vincent JL, Wendon J, Zampieri FG, Rhodes A, Moreno R. Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score. JAMA. 2025 Dec 16;334(23):2090-2103. doi: 10.1001/jama.2025.20516.
PubMed 41159833Ong SWX, Petersiel N, Loewenthal MR, Daneman N, Tong SYC, Davis JS. Unlocking the DOOR-how to design, apply, analyse, and interpret desirability of outcome ranking endpoints in infectious diseases clinical trials. Clin Microbiol Infect. 2023 Aug;29(8):1024-1030. doi: 10.1016/j.cmi.2023.05.003. Epub 2023 May 12.
PubMed 37179006Costa EL, Borges JB, Melo A, Suarez-Sipmann F, Toufen C Jr, Bohm SH, Amato MB. Bedside estimation of recruitable alveolar collapse and hyperdistension by electrical impedance tomography. Intensive Care Med. 2009 Jun;35(6):1132-7. doi: 10.1007/s00134-009-1447-y. Epub 2009 Mar 3.
PubMed 19255741Be'eri E, Ming J, Dan-nuo H, Jianxin Z, Min X, Zhong-hua S, et al. In-line Mechanical Insufflation-Exsufflation as an Alternative to Invasive Suction for Secretion Management in Ventilated Patients, a Randomized Controlled Trial. Tracheostomy. 2024;1(1):18-25.
van Saene HK, Ashworth M, Petros AJ, Sanchez M, de la Cal MA. Do not suction above the cuff. Crit Care Med. 2004 Oct;32(10):2160-2. doi: 10.1097/01.ccm.0000142902.24268.cc. No abstract available.
PubMed 15483436Pozuelo-Carrascosa DP, Herraiz-Adillo A, Alvarez-Bueno C, Anon JM, Martinez-Vizcaino V, Cavero-Redondo I. Subglottic secretion drainage for preventing ventilator-associated pneumonia: an overview of systematic reviews and an updated meta-analysis. Eur Respir Rev. 2020 Feb 12;29(155):190107. doi: 10.1183/16000617.0107-2019. Print 2020 Mar 31.
PubMed 32051169Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, Fernandez R, Baigorri F, Mestre J. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med. 1995 Feb 1;122(3):179-86. doi: 10.7326/0003-4819-122-3-199502010-00004.
PubMed 7810935Sanchez-Garcia M, Alvarez-Gonzalez M, Domingo-Marin S, Pino-Ramirez AD, Martinez-Sagasti F, Gonzalez-Arenas P, Cardenal-Sanchez C, Velasco-Lopez E, Nunez-Reiz A. Comparison of Mechanical Insufflation-Exsufflation and Hypertonic Saline and Hyaluronic Acid With Conventional Open Catheter Suctioning in Intubated Patients. Respir Care. 2024 Apr 22;69(5):575-585. doi: 10.4187/respcare.11566.
PubMed 38307525Puntillo KA, Max A, Timsit JF, Vignoud L, Chanques G, Robleda G, Roche-Campo F, Mancebo J, Divatia JV, Soares M, Ionescu DC, Grintescu IM, Vasiliu IL, Maggiore SM, Rusinova K, Owczuk R, Egerod I, Papathanassoglou ED, Kyranou M, Joynt GM, Burghi G, Freebairn RC, Ho KM, Kaarlola A, Gerritsen RT, Kesecioglu J, Sulaj MM, Norrenberg M, Benoit DD, Seha MS, Hennein A, Periera FJ, Benbenishty JS, Abroug F, Aquilina A, Monte JR, An Y, Azoulay E. Determinants of procedural pain intensity in the intensive care unit. The Europain(R) study. Am J Respir Crit Care Med. 2014 Jan 1;189(1):39-47. doi: 10.1164/rccm.201306-1174OC.
PubMed 24262016Latorre-Marco I, Acevedo-Nuevo M, Solis-Munoz M, Hernandez-Sanchez L, Lopez-Lopez C, Sanchez-Sanchez MM, Wojtysiak-Wojcicka M, de Las Pozas-Abril J, Robleda-Font G, Frade-Mera MJ, De Blas-Garcia R, Gorgolas-Ortiz C, De la Figuera-Bayon J, Cavia-Garcia C. Psychometric validation of the behavioral indicators of pain scale for the assessment of pain in mechanically ventilated and unable to self-report critical care patients. Med Intensiva. 2016 Nov;40(8):463-473. doi: 10.1016/j.medin.2016.06.004. Epub 2016 Aug 31. English, Spanish.
PubMed 27590592American Association for Respiratory Care. AARC Clinical Practice Guidelines. Endotracheal suctioning of mechanically ventilated patients with artificial airways 2010. Respir Care. 2010 Jun;55(6):758-64.
PubMed 20507660Alvarez-Lerma F, Palomar-Martinez M, Sanchez-Garcia M, Martinez-Alonso M, Alvarez-Rodriguez J, Lorente L, Arias-Rivera S, Garcia R, Gordo F, Anon JM, Jam-Gatell R, Vazquez-Calatayud M, Agra Y. Prevention of Ventilator-Associated Pneumonia: The Multimodal Approach of the Spanish ICU "Pneumonia Zero" Program. Crit Care Med. 2018 Feb;46(2):181-188. doi: 10.1097/CCM.0000000000002736.
PubMed 29023261Sanchez Garcia M, Cambronero Galache JA, Lopez Diaz J, Cerda Cerda E, Rubio Blasco J, Gomez Aguinaga MA, Nunez Reiz A, Rogero Marin S, Onoro Canaveral JJ, Sacristan del Castillo JA. Effectiveness and cost of selective decontamination of the digestive tract in critically ill intubated patients. A randomized, double-blind, placebo-controlled, multicenter trial. Am J Respir Crit Care Med. 1998 Sep;158(3):908-16. doi: 10.1164/ajrccm.158.3.9712079.
PubMed 9731025Francois B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, Guitton C, Deye N, Legriel S, Plantefeve G, Quenot JP, Desachy A, Kamel T, Bedon-Carte S, Diehl JL, Chudeau N, Karam E, Durand-Zaleski I, Giraudeau B, Vignon P, Le Gouge A; CRICS-TRIGGERSEP Network and the ANTHARTIC Study Group. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019 Nov 7;381(19):1831-1842. doi: 10.1056/NEJMoa1812379.
PubMed 31693806