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NCT Number: NCT06203405

The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial

This clinical trial aims to assess the efficacy of sedation protocol targeting optimal respiratory drive using P0.1 and arousal level compared with conventional sedation strategy (targeting arousal level alone) in patients requiring mechanical ventilation in the medical intensive care unit.

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Key information

Conditions

Respiratory Failure Critical Illness Disease Attributes Lung Diseases Lung Injury Mechanical Ventilation Complication Pathologic Processes Pathological Conditions, Signs and Symptoms Respiration Disorders Respiratory Distress Syndrome Respiratory Distress Syndrome, Adult Respiratory Insufficiency Respiratory Tract Diseases Thoracic Injuries Wounds and Injuries

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Siriraj Hospital

Bangkok, 10700, Thailand

Location status: Recruiting

Location contact

Adhiratha Boonyasiri, MD

SUB_INVESTIGATOR

Akekarin Poompichet, MD

SUB_INVESTIGATOR

Chailat Maluangnon, MD

SUB_INVESTIGATOR

Chairat Permpikul, MD

SUB_INVESTIGATOR

Metanee Promlungka, RN

SUB_INVESTIGATOR

Natdanai Ketdao, MD

CONTACT

[email protected]

+66880684998

Natdanai Ketdao, MD

SUB_INVESTIGATOR

Nattapat Wongtirawit, MD

SUB_INVESTIGATOR

Nualnapa Kasemvilawan, RN

SUB_INVESTIGATOR

Panuwat Promsin, MD

SUB_INVESTIGATOR

Preecha Thomrongpairoj, MD

SUB_INVESTIGATOR

Ranistha Ratanarat, MD

SUB_INVESTIGATOR

Surat Tongyoo, MD

SUB_INVESTIGATOR

Tanuwong Viarasilpa, MD

CONTACT

[email protected]

+66813469400

Tanuwong Viarasilpa, MD

PRINCIPAL_INVESTIGATOR

Thummaporn Naorungroj, MD

SUB_INVESTIGATOR

About this study

Objective: to assess the efficacy of sedation protocol targeting optimal respiratory drive using P0.1 and RASS score compared with conventional sedation strategy (targeting RASS score alone) in patients requiring mechanical ventilation in the medical intensive care unit

The main questions it aims to answer are:

  • Will titration of sedation targeting optimal respiratory drive assessed by P0.1 and arousal level improve outcomes in patients requiring mechanical ventilation in the medical ICU?

Study protocol Mechanically ventilated patients admitted to the medical ICU will be screened daily by the investigators. If the patients meet the eligibility criteria, they will be informed about the study protocol and potential risks and undergo informed consent. Then patients will be randomized in a 1:1 ratio and allocated to each study group (intervention and control group).

  • After allocation, patients will be monitored for arousal level using RASS score and respiratory drive by P0.1 measured automatically from mechanical ventilators during the study period.
  • Sedation and neuromuscular blocking agents used will be adjusted according to the group to which patients are allocated.
  • Intervention group: Adjustment of sedation and neuromuscular blocking agents to achieve the target of light sedation (RASS 0 to -2) and optimal P0.1 (1.5 to 3.5 cmH2O) for 48 hours
  • Control group: Adjustment of sedation to achieve the target of light sedation (RASS 0 to -2) alone for 48 hours

Researchers will compare the outcomes (rate of successful extubation, ICU and hospital mortality, ICU and hospital length of stay, duration of mechanical ventilation, amount and duration of sedation used during the study period) between the above sedation protocol (interventional group) and conventional sedation strategy (control group)

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Patients admitted to the medical intensive care unit at Department of Medicine, Siriraj Hospital
  • Age ≥18 years old
  • Receiving mechanical ventilation due to acute respiratory failure within 72 hours before enrollment (including patients receiving mechanical ventilation before ICU admission)

Exclusion criteria

  • Patients receiving mechanical ventilation due to indications other than acute respiratory failure, such as postoperative procedures or airway protection in comatose patients
  • Patients receiving mechanical ventilation for >72 hours before enrollment
  • Patients receiving neuromuscular blocking agents prior to randomization
  • Patients with impaired secretion clearance or upper airway obstruction anticipating a tracheostomy
  • Patients with severe metabolic acidosis (arterial pH <7.2) who do not have a plan for renal replacement therapy
  • Patients intubated for neurological conditions, including intracranial hypertension, intracranial hemorrhage, large cerebral infarction, status epilepticus, or neuromuscular diseases
  • Post-cardiac arrest patients
  • Patients with severe liver dysfunction, including acute fulminant liver failure or cirrhosis with the Child-Pugh score B or C
  • Patients who have a previous allergy to any of the opioid, sedation, or neuromuscular blocking drugs
  • Pregnancy
  • Patients with do-not-resuscitate (DNR) orders or decisions to withhold life-sustaining treatments
  • Patients who refuse to participate in the study or cannot identify legally authorized representatives (LAR) within 24 hours after enrollment

Treatment and study plan

Titrating sedation targeting both optimal P0.1 and appropriate arousal level

Procedure
  • Sedation will be adjusted initially to target light sedation (RASS 0 to -2).
  • Sedative drugs include IV fentanyl (25-75 mcg/h), midazolam (0.02- 0.1 mg/kg/h), propofol (5-50 mcg/kg/min), dexmedetomidine (0.2-0.7 mcg/kg/h).
  • Deep sedation and neuromuscular blocking agents are allowed to facilitate mechanical ventilation adjustment in patients with refractory hypoxemia.
  • Dose of cisatracurium is 0.15-0.2 mg/kg intravenous bolus, then continuous infusion at 5 -20 mg/h.
  • Then sedation adjustment will be guided by P0.1 measurement.
  • If P0.1 value of 1.5-3.5 cmH2O is achieved, no further adjustment is required.
  • If P0.1 value <1.5, sedation will be reduced.
  • If P0.1 value >3.5, sedation will be increased.
  • If P0.1 value is still >3.5 with deep sedation, cisatracurium will be allowed and titrated until P0.1 value <3.5 cmH2O.
  • The study protocol will be continued for 48 hours or until the patients are considered ready for weaning.

Fentanyl

Drug

Continuous intravenous infusion of fentanyl 25-75 micrograms/hour

midazolam

Drug

Continuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour

Propofol

Drug

Continuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute

Dexmedetomidine

Drug

Continuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour

Cisatracurium

Drug

Continuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour

Primary outcomes

  1. Successful extubation within 14 days after randomization

    Time frame: 14 days after randomization

    Successful extubation within 14 days without reintubation within 28 days after ICU admission

Secondary outcomes

  1. Successful extubation within 7 days after randomization

    Time frame: 7 days after randomization

    Successful extubation within 7 days without reintubation within 28 days after ICU admission

  2. Successful extubation within 28 days after randomization

    Time frame: 28 days after randomization

    Successful extubation without reintubation within 28 days after ICU admission

  3. Duration of mechanical ventilation

    Time frame: From date of intubation until the date of last successful extubation or date of death from any cause, whichever came first, assessed up to 28 days

    Time from intubation to the last successful extubation

  4. Ventilator-free days to day 28 after randomization

    Time frame: 28 days after randomization

    Number of days alive without mechanical ventilation

  5. Reintubation rate at 7 days after randomization

    Time frame: 7 days after randomization

    Number of reintubation within 7 days after randomization

  6. Self extubation rate at 7 days after extubation

    Time frame: 7 days after randomization

    Number of self extubation (accidentally extubation without physician's order) within 7 days after randomization

  7. Post-extubation respiratory failure

    Time frame: From date of randomization until the date of the first event of post-extubation respiratory failure or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days

    Patients who meet at least one of the following criteria within 72 hours after extubation: respiratory rate more than 35 breaths/minute, oxygen saturation less than 90% or PaO2 less than 80 mmHg despite receiving FiO2 >50%, respiratory acidosis with pH <7.35 or PaCO2 >50 mmHg or increase of 20% from baseline.

  8. Tracheostomy

    Time frame: From date of randomization until the date of tracheostomy or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days

    Number of tracheostomy performed

  9. Lung injury score on day 3 after randomization

    Time frame: 3 days after randomization

    Lung injury score on day 3 after randomization

  10. Lung injury score on day 7 after randomization

    Time frame: 7 days after randomization

    Lung injury score on day 7 after randomization

  11. PaO2/FiO2 ratio on day 3 after randomization

    Time frame: 3 days after randomization

    PaO2/FiO2 ratio on day 3 after randomization

  12. PaO2/FiO2 ratio on day 7 after randomization

    Time frame: 7 days after randomization

    PaO2/FiO2 ratio on day 7 after randomization

  13. Rates of new diagnosis of ARDS according to the new Berlin criteria after randomization

    Time frame: From date of randomization until the date of new onset ARDS diagnosis after randomization or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days

    Number of ARDS diagnoses after randomization

  14. Delirium during ICU admission

    Time frame: From date of randomization until the date of diagnosis of delirium diagnosis or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days

    Delirium assessed by positive CAM-ICU criteria during ICU admission

  15. Glasgow Outcome Scale (GOS) at hospital discharge

    Time frame: From date of randomization until the date of hospital discharge or date of death from any cause , whichever came first, assessed up to 28 days

    Functional status assessed by Glasgow Outcome Scale (GOS) at hospital discharge

    • Unabbreviated title: Glasgow Outcome Scale
    • Maximum score: 5 = good recovery
    • 4 = Moderate disability, 3 = Severe disability, 2 = Vegetative state
    • Minimum score: 1 = death (Higher scores mean better outcome)

  16. ICU all-cause mortality

    Time frame: From date of randomization until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days

    All-cause mortality during ICU admission

  17. Hospital all-cause mortality

    Time frame: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 28 days

    All-cause mortality during hospital admission

  18. 28-day mortality after randomization

    Time frame: 28 days after randomization

    All-cause mortality during 28-day after randomization

  19. ICU length of stay

    Time frame: From date of randomization until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days

    Time from ICU admission to ICU discharge

  20. Hospital length of stay

    Time frame: From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 28 days

    Time from hospital admission to hospital discharge

  21. Maximum infusion dose (per hour) of sedation

    Time frame: From date of sedation initiation until the date of sedation discontinuation or date of death from any cause, whichever came first, assessed up to 28 days

    Maximum infusion dose (per hour) of sedation used during the study period

  22. Duration (days) of sedation

    Time frame: From date of sedation initiation until the date of sedation discontinuation or date of death from any cause, whichever came first, assessed up to 28 days

    Duration (days) of sedation used during the study period

  23. Ventilator-associated pneumonia

    Time frame: From date of randomization until the date of first diagnosed ventilator-associated pneumonia or date of death from any cause, whichever came first, assessed up to 28 days

    Number of ventilator-associated pneumonia diagnosed after randomization

  24. Barotrauma

    Time frame: From date of randomization until the date of first documented barotrauma or date of death from any cause, whichever came first, assessed up to 28 days

    Number of barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema) occurred after randomization

  25. Serious adverse events

    Time frame: From date of randomization until the date of first documented serious adverse events or date of death from any cause, whichever came first, assessed up to 28 days

    Number of serious adverse events (severe allergic reaction or anaphylaxis and propofol infusion syndrome defined as severe lactic acidosis and hypertriglyceridemia) occurred after randomization

  26. Cardiac arrhythmia

    Time frame: From date of randomization until the date of first documented cardiac arrhythmia events or date of death from any cause, whichever came first, assessed up to 28 days

    Number of cardiac arrhythmia events occurred after randomization

  27. Maximum infusion dose (per hour) of vasopressor

    Time frame: From date of vasopressor initiation until the date of vasopressor discontinuation or date of death from any cause, whichever came first, assessed up to 28 days

    Maximum infusion dose (per hour) of vasopressor used during the study period

  28. Duration (days) of vasopressor

    Time frame: From date of vasopressor initiation until the date of vasopressor discontinuation or date of death from any cause, whichever came first, assessed up to 28 days

    Duration (days) of vasopressor used during the study period

Study contacts

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

Natdanai Ketdao, MD

CONTACT

[email protected]

+66880684998

Tanuwong Viarasilpa, MD

CONTACT

[email protected]

+66813469400

Sponsors and collaborators

Lead sponsor

Siriraj Hospital

Other

Registry information

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Jan 12, 2024
Registry last updated
May 22, 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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