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NCT Number: NCT06776939

Physiological Effect High-flow Tracheal Oxygen on Viscosity of Airway Mucus and Respiratory Effort in Patients Weaning from Invasive Mechanical Ventilation

Rationale: Tracheostomized patients weaning from mechanical ventilation are at risk for dryness of airway mucosa and sputum accumulation during disconnection from mechanical ventilation. High-flow tracheal oxygen (HFTO) is being used as supportive therapy during disconnection sessions in tracheostomized patients weaning from invasive mechanical ventilation (IMV) to limit dryness while maintaining oxygenation. We recently summarized the studies comparing physiological effects HFTO as compared to other interfaces, collectively referred to as conventional oxygen therapy (COT), in a systematic review and identified areas of lacking knowledge: effect on sputum viscoelasticity, respiratory effort early in the weaning process and dyspnea sensation. We hypothesize that HFTO, compared to COT, decreases viscoelasticity of the sputum and provides respiratory support during weaning. This may improve weaning by facilitating clearance of airway mucus, preventing respiratory failure, and providing comfort by decreasing dyspnea.

Objective: To determine the physiological effect of HFTO compared to COT on sputum viscoelasticity, respiratory effort and dyspnoea.

Study design: Pilot study with randomized crossover design, single-center. Study population: Twenty adult patients weaning from mechanical ventilation with tracheostomy.

Intervention (if applicable): Crossover with COT and HFTO during two days in the weaning phase.

Main study parameters/endpoints: Primary endpoint: sputum viscoelasticity measured by rheology during long disconnection sessions in the final phase of weaning. Secondary endpoints: respiratory effect measured by swings in esophageal pressure (PES) and prevalence and severity of dyspnoea sensation by visual analogue scale (VAS).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The study compares two therapeutic modalities both used in clinical care without side-effects or complications. Study procedures and measurements consist of standard clinical procedures that are performed daily in clinical setting with negligible risk of deterioration for the patient. During weaning with HFTO sputum clearance might be more easy for the patient and respiratory effort might decrease, both are assumed to be beneficial for the weaning process of the patient.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Erasmus Medical Center

Rotterdam, 3015, Netherlands

Location status: Recruiting

Location contact

Thijs Janssen, MD

CONTACT

[email protected]

010-7035142

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion:

  • Age ≥18 years
  • Weaning from mechanical ventilation with tracheostomy

Exclusion criteria

  • Longstanding tracheostomy, defined as tracheostomy being present prior to current hospital admission
  • Tracheostomy primarily indicated for chronic upper airway obstruction or to secure airway patency due to persistent stupor/coma
  • Chronic positive pressure respiratory support at home (excluding night-time continuous positive airway pressure for sleep apnea)
  • Mucociliary disease in medical history (e.g. cystic fibrosis, pulmonary ciliary dyskinesia)
  • Neuromuscular disease in medical history (excluding ICU-acquired weakness)
  • Contra-indication placement oesophageal balloon for measurement of PES, such as:
  • Fractures in mandibular, orbital or ethmoid bone or skull base
  • Esophageal varices or surgery in medical history
  • Severe bleeding disorders
  • Hemoptysis in 72 hours prior to the first disconnection session. Clinically relevant hemoptysis is defined as hemoptysis requiring tracheal/endobronchial or radiologic intervention, or administration of pro-coagulating drugs such as tranexamic acid.

Treatment and study plan

Oxygen therapy

Device

All patients are subject to both oxygen therapy groups in this randomized cross-over study. Study measurements are performed during several different disconnection sessions. Disconnection sessions can either be short (<90 min) or long (12 hours). Both short and long disconnection sessions are performed twice; once with conventional oxygen, and once with high-flow tracheal oxygen as respiratory support.

Primary outcomes

  1. Sputum viscoelasticity

    Time frame: The 12-hour disconnection session

    During disconnection from the ventilator patients do not breathe actively heated and humidified gas mixtures. During disconnection from the ventilator the airway mucus thickens. This thickening can be quantified by measuring visco-elasticity and at the end of the disconnection sessions. The change in visco-elasticity between the start and end of the disconnection session will be compared within patients between disconnection sessions with HME and HFTO. Hence, the primary end-point is the change in sputum viscoelasticity from baseline to the end of the long disconnection sessions (≥12 hours). Viscoelastic (G*) is made up of elasticity (G') and viscosity (G'') of mucus at a 5% strain rate (or linear viscoelastic region, which reflects the small deformation regime) and the critical stress (σ critical)· and strain (y critical) of mucus, which reflect the behavior of mucus under high amounts of shear stress and thus the large deformation regime.

Secondary outcomes

  1. Sputum visco-elasiticity

    Time frame: The short disconnection session (<90 minutes)

    The difference between COT and HFTO in change in sputum viscoelasticity from baseline to the end (after 10-90 min) of the early disconnection session

  2. Dyspnea presence

    Time frame: At early (<90 min) and late (12 hour) disconnection sessions

    The presence of self-reported dyspnea sensation during early (<90 min) and late (12 hour) disconnection sessions. Presence of self-reported dyspnea and discomfort is evaluated by asking patients.

  3. Respiratory effort

    Time frame: The short disconnection session (<90 minutes)

    The difference in respiratory effort between conventional oxygen therapy and high-flow oxygen therapy during early disconnection sessions measured by median esophageal pressure swing and pressure time product during the early disconnection session.

  4. Dyspnea severity

    Time frame: early (<90 min) and late (12 hour) disconnection sessions

    The severity of self-reported dyspnea sensation during early (<90 min) and late (12 hour) disconnection sessions. Severity of self-reported dyspnea is evaluated using a dyspnea visual-analog scale (D-VAS)

Study contacts

Contact information is provided by the study sponsor or research team.

Henrik Endeman Intensivist, Assistant Professor Intensive Care, MD, PhD

CONTACT

[email protected]

0107035142

Thijs Janssen Resident pulmonology, Critical Care researcher, MD

CONTACT

[email protected]

0107035142

Sponsors and collaborators

Lead sponsor

Henrik Endeman

Other

Collaborators

  • Fisher and Paykel Healthcare

Registry information

Acronym: PIONEER

Important dates

Study start
2025
Primary completion
2025
Study completion
2026
First posted
Jan 15, 2025
Registry last updated
Jan 15, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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