Respiratory FailureNCT06203405
The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial
A study testing Titrating sedation targeting both optimal P0.1 and appropriate arousal level, Fentanyl and Midazolam in people with Respiratory Failure and Critical Illness, run by Siriraj Hospital at 1 site in Thailand.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Respiratory Failure, Critical Illness, Respiratory Distress Syndrome, Adult
- What is being tested?
- Titrating sedation targeting both optimal P0.1 and appropriate arousal level, Fentanyl and Midazolam
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 1 siteThailand
- Study dates
- 22 Dec 2023to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- 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)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Thailand1 site, 1 recruiting
- Recruiting
Siriraj Hospital
Bangkok, Bangkok, 10700
Natdanai Ketdao, MD, +66880684998, natdke@kku.ac.th
Tanuwong Viarasilpa, MD, +66813469400, tanuwong.via@mahidol.ac.th
About this study
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.
Read the detailed description
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)
- Conditions
- Respiratory Failure, Critical Illness, Respiratory Distress Syndrome, Adult, Lung Injury, Mechanical Ventilation Complication
- Being tested
- Titrating sedation targeting both optimal P0.1 and appropriate arousal level, Fentanyl, Midazolam, Propofol, Dexmedetomidine
- Keywords
- acute respiratory failure, sedation, respiratory drive monitoring, mechanical ventilation, intensive care unit
- Medical subject headings
- Respiratory Insufficiency, Critical Illness, Respiratory Distress Syndrome, Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Titrating sedation targeting both optimal P0.1 and appropriate arousal levelProcedure or surgery
- 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.
FentanylDrug
Continuous intravenous infusion of fentanyl 25-75 micrograms/hour
MidazolamDrug
Continuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour
PropofolDrug
Continuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute
DexmedetomidineDrug
Continuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour
CisatracuriumDrug
Continuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour
| Study group | Role | What they receive |
|---|---|---|
| Titrating sedation targeting both optimal P0.1 and appropriate arousal level | Experimental | • Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) and optimal respiratory drive measured by P0.1 of 1.5 - 3.5 cmH2O Receives: Procedure: Titrating sedation targeting both optimal P0.1 and appropriate arousal level; Drug: Fentanyl; Drug: Midazolam; Drug: Propofol; Drug: Dexmedetomidine; Drug: Cisatracurium |
| Titrating sedation targeting appropriate arousal level alone | No intervention | • Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) according to the standard clinical practice guidelines for managing pain and agitation for patients receiving mechanical ventilation in the ICU. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful extubation within 14 days after randomization
Successful extubation within 14 days without reintubation within 28 days after ICU admission
Measured: 14 days after randomization
Secondary outcomes (28)
Successful extubation within 7 days after randomization
Successful extubation within 7 days without reintubation within 28 days after ICU admission
Measured: 7 days after randomization
Successful extubation within 28 days after randomization
Successful extubation without reintubation within 28 days after ICU admission
Measured: 28 days after randomization
Duration of mechanical ventilation
Time from intubation to the last successful extubation
Measured: 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
Ventilator-free days to day 28 after randomization
Number of days alive without mechanical ventilation
Measured: 28 days after randomization
Reintubation rate at 7 days after randomization
Number of reintubation within 7 days after randomization
Measured: 7 days after randomization
Self extubation rate at 7 days after extubation
Number of self extubation (accidentally extubation without physician's order) within 7 days after randomization
Measured: 7 days after randomization
Post-extubation respiratory failure
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.
Measured: 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
Tracheostomy
Number of tracheostomy performed
Measured: 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
Lung injury score on day 3 after randomization
Lung injury score on day 3 after randomization
Measured: 3 days after randomization
Lung injury score on day 7 after randomization
Lung injury score on day 7 after randomization
Measured: 7 days after randomization
PaO2/FiO2 ratio on day 3 after randomization
PaO2/FiO2 ratio on day 3 after randomization
Measured: 3 days after randomization
PaO2/FiO2 ratio on day 7 after randomization
PaO2/FiO2 ratio on day 7 after randomization
Measured: 7 days after randomization
Rates of new diagnosis of ARDS according to the new Berlin criteria after randomization
Number of ARDS diagnoses after randomization
Measured: 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
Delirium during ICU admission
Delirium assessed by positive CAM-ICU criteria during ICU admission
Measured: 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
Glasgow Outcome Scale (GOS) at hospital discharge
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)
Measured: 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
ICU all-cause mortality
All-cause mortality during ICU admission
Measured: 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
Hospital all-cause mortality
All-cause mortality during hospital admission
Measured: 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
28-day mortality after randomization
All-cause mortality during 28-day after randomization
Measured: 28 days after randomization
ICU length of stay
Time from ICU admission to ICU discharge
Measured: 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
Hospital length of stay
Time from hospital admission to hospital discharge
Measured: 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
Maximum infusion dose (per hour) of sedation
Maximum infusion dose (per hour) of sedation used during the study period
Measured: 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
Duration (days) of sedation used during the study period
Measured: 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
Ventilator-associated pneumonia
Number of ventilator-associated pneumonia diagnosed after randomization
Measured: 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
Barotrauma
Number of barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema) occurred after randomization
Measured: 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
Serious adverse events
Number of serious adverse events (severe allergic reaction or anaphylaxis and propofol infusion syndrome defined as severe lactic acidosis and hypertriglyceridemia) occurred after randomization
Measured: 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
Cardiac arrhythmia
Number of cardiac arrhythmia events occurred after randomization
Measured: 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
Maximum infusion dose (per hour) of vasopressor
Maximum infusion dose (per hour) of vasopressor used during the study period
Measured: 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
Duration (days) of vasopressor used during the study period
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study start22 Dec 2023
- Primary completion31 Mar 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (37)Papers the sponsor has linked to this study.
- Other trials for Respiratory FailureStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Siriraj Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Natdanai Ketdao, Siriraj Hospital
- Investigators
- Tanuwong Viarasilpa, MD, Principal investigator, Division of Critical Care, Department of Medicine, Siriraj Hospital, Mahidol UniversityNatdanai Ketdao, MD, Principal investigator, Division of Critical Care, Department of Medicine, Siriraj Hospital, Mahidol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06203405
- Sponsor's protocol ID
- SI915/2023
- Status last verified
- May 2025
- First submitted
- 7 Dec 2023
- Last updated
- 22 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in a publication of this study (after deidentification)
Publications
Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP.
PubMed 27626833Sklienka P, Frelich M, Bursa F. Patient Self-Inflicted Lung Injury-A Narrative Review of Pathophysiology, Early Recognition, and Management Options. J Pers Med. 2023 Mar 28;13(4):593. doi: 10.3390/jpm13040593.
PubMed 37108979Carteaux G, Parfait M, Combet M, Haudebourg AF, Tuffet S, Mekontso Dessap A. Patient-Self Inflicted Lung Injury: A Practical Review. J Clin Med. 2021 Jun 21;10(12):2738. doi: 10.3390/jcm10122738.
PubMed 34205783Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D. Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions. Intensive Care Med. 2020 Apr;46(4):606-618. doi: 10.1007/s00134-020-05942-6. Epub 2020 Feb 3.
PubMed 32016537Spinelli E, Pesenti A, Slobod D, Fornari C, Fumagalli R, Grasselli G, Volta CA, Foti G, Navalesi P, Knafelj R, Pelosi P, Mancebo J, Brochard L, Mauri T. Clinical risk factors for increased respiratory drive in intubated hypoxemic patients. Crit Care. 2023 Apr 11;27(1):138. doi: 10.1186/s13054-023-04402-z.
PubMed 37041553Chanques G, Constantin JM, Devlin JW, Ely EW, Fraser GL, Gelinas C, Girard TD, Guerin C, Jabaudon M, Jaber S, Mehta S, Langer T, Murray MJ, Pandharipande P, Patel B, Payen JF, Puntillo K, Rochwerg B, Shehabi Y, Strom T, Olsen HT, Kress JP. Analgesia and sedation in patients with ARDS. Intensive Care Med. 2020 Dec;46(12):2342-2356. doi: 10.1007/s00134-020-06307-9. Epub 2020 Nov 10.
PubMed 33170331Goligher EC, Jonkman AH, Dianti J, Vaporidi K, Beitler JR, Patel BK, Yoshida T, Jaber S, Dres M, Mauri T, Bellani G, Demoule A, Brochard L, Heunks L. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med. 2020 Dec;46(12):2314-2326. doi: 10.1007/s00134-020-06288-9. Epub 2020 Nov 2.
PubMed 33140181Dzierba AL, Khalil AM, Derry KL, Madahar P, Beitler JR. Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation. Crit Care Med. 2021 Dec 1;49(12):2090-2101. doi: 10.1097/CCM.0000000000005113.
PubMed 34115638Wongtangman K, Grabitz SD, Hammer M, Wachtendorf LJ, Xu X, Schaefer MS, Fassbender P, Santer P, Kassis EB, Talmor D, Eikermann M; SICU Optimal Mobilization Team (SOMT) Group. Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network. Crit Care Med. 2021 Jul 1;49(7):1137-1148. doi: 10.1097/CCM.0000000000004951.
PubMed 33710031Jackson DL, Proudfoot CW, Cann KF, Walsh TS. The incidence of sub-optimal sedation in the ICU: a systematic review. Crit Care. 2009;13(6):R204. doi: 10.1186/cc8212. Epub 2009 Dec 16.
PubMed 20015357Kassis EB, Beitler JR, Talmor D. Lung-protective sedation: moving toward a new paradigm of precision sedation. Intensive Care Med. 2023 Jan;49(1):91-94. doi: 10.1007/s00134-022-06901-z. Epub 2022 Oct 14. No abstract available.
PubMed 36239747Bertoni M, Spadaro S, Goligher EC. Monitoring Patient Respiratory Effort During Mechanical Ventilation: Lung and Diaphragm-Protective Ventilation. Crit Care. 2020 Mar 24;24(1):106. doi: 10.1186/s13054-020-2777-y.
PubMed 32204729Rittayamai N, Beloncle F, Goligher EC, Chen L, Mancebo J, Richard JM, Brochard L. Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort. Ann Intensive Care. 2017 Oct 6;7(1):100. doi: 10.1186/s13613-017-0324-z.
PubMed 28986852Telias I, Junhasavasdikul D, Rittayamai N, Piquilloud L, Chen L, Ferguson ND, Goligher EC, Brochard L. Airway Occlusion Pressure As an Estimate of Respiratory Drive and Inspiratory Effort during Assisted Ventilation. Am J Respir Crit Care Med. 2020 May 1;201(9):1086-1098. doi: 10.1164/rccm.201907-1425OC.
PubMed 32097569Beloncle F, Piquilloud L, Olivier PY, Vuillermoz A, Yvin E, Mercat A, Richard JC. Accuracy of P0.1 measurements performed by ICU ventilators: a bench study. Ann Intensive Care. 2019 Sep 13;9(1):104. doi: 10.1186/s13613-019-0576-x.
PubMed 31520230
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT06203405
- Acronym / sponsor ID
- SI915/2023
- Conditions
- Respiratory Failure, Critical Illness, Respiratory Distress Syndrome, Adult, Lung Injury, Mechanical Ventilation Complication
- Keywords
- acute respiratory failure, sedation, respiratory drive monitoring, mechanical ventilation, intensive care unit
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Siriraj HospitalUniversity, hospital or other
- Study start
- 22 Dec 2023 (actual)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 12 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Titrating sedation targeting both optimal P0.1 and appropriate arousal level | Experimental | Procedure: Titrating sedation targeting both optimal P0.1 and appropriate arousal level, Drug: Fentanyl, Drug: Midazolam, Drug: Propofol, Drug: Dexmedetomidine, Drug: Cisatracurium• Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) and optimal respiratory drive measured by P0.1 of 1.5 - 3.5 cmH2O |
| Titrating sedation targeting appropriate arousal level alone | No intervention | –• Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) according to the standard clinical practice guidelines for managing pain and agitation for patients receiving mechanical ventilation in the ICU. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Titrating sedation targeting both optimal P0.1 and appropriate arousal level* 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. | Procedure or surgery | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
| FentanylContinuous intravenous infusion of fentanyl 25-75 micrograms/hour | Drug | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
| MidazolamContinuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour | Drug | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
| PropofolContinuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute | Drug | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
| DexmedetomidineContinuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour | Drug | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
| CisatracuriumContinuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour | Drug | Titrating sedation targeting both optimal P0.1 and appropriate arousal level |
Primary outcome
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
28 secondary outcomes
Successful extubation within 7 days after randomization
Time frame: 7 days after randomization
Successful extubation within 28 days after randomization
Time frame: 28 days after randomization
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
Ventilator-free days to day 28 after randomization
Time frame: 28 days after randomization
Reintubation rate at 7 days after randomization
Time frame: 7 days after randomization
Self extubation rate at 7 days after extubation
Time frame: 7 days after randomization
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
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
Lung injury score on day 3 after randomization
Time frame: 3 days after randomization
Lung injury score on day 7 after randomization
Time frame: 7 days after randomization
PaO2/FiO2 ratio on day 3 after randomization
Time frame: 3 days after randomization
PaO2/FiO2 ratio on day 7 after randomization
Time frame: 7 days after randomization
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
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
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
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
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
28-day mortality after randomization
Time frame: 28 days after randomization
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
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
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
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
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
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
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
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2025.
- Background: PubMed 27626833Brochard L, Slutsky A, Pesenti A. Mechanical Ventilation to Minimize Progression of Lung Injury in Acute Respiratory Failure. Am J Respir Crit Care Med. 2017 Feb 15;195(4):438-442. doi: 10.1164/rccm.201605-1081CP.
- Background: PubMed 37108979Sklienka P, Frelich M, Bursa F. Patient Self-Inflicted Lung Injury-A Narrative Review of Pathophysiology, Early Recognition, and Management Options. J Pers Med. 2023 Mar 28;13(4):593. doi: 10.3390/jpm13040593.
- Background: PubMed 34205783Carteaux G, Parfait M, Combet M, Haudebourg AF, Tuffet S, Mekontso Dessap A. Patient-Self Inflicted Lung Injury: A Practical Review. J Clin Med. 2021 Jun 21;10(12):2738. doi: 10.3390/jcm10122738.
- Background: PubMed 32016537Spinelli E, Mauri T, Beitler JR, Pesenti A, Brodie D. Respiratory drive in the acute respiratory distress syndrome: pathophysiology, monitoring, and therapeutic interventions. Intensive Care Med. 2020 Apr;46(4):606-618. doi: 10.1007/s00134-020-05942-6. Epub 2020 Feb 3.
- Background: PubMed 37041553Spinelli E, Pesenti A, Slobod D, Fornari C, Fumagalli R, Grasselli G, Volta CA, Foti G, Navalesi P, Knafelj R, Pelosi P, Mancebo J, Brochard L, Mauri T. Clinical risk factors for increased respiratory drive in intubated hypoxemic patients. Crit Care. 2023 Apr 11;27(1):138. doi: 10.1186/s13054-023-04402-z.
- Background: PubMed 33170331Chanques G, Constantin JM, Devlin JW, Ely EW, Fraser GL, Gelinas C, Girard TD, Guerin C, Jabaudon M, Jaber S, Mehta S, Langer T, Murray MJ, Pandharipande P, Patel B, Payen JF, Puntillo K, Rochwerg B, Shehabi Y, Strom T, Olsen HT, Kress JP. Analgesia and sedation in patients with ARDS. Intensive Care Med. 2020 Dec;46(12):2342-2356. doi: 10.1007/s00134-020-06307-9. Epub 2020 Nov 10.
- Background: PubMed 33140181Goligher EC, Jonkman AH, Dianti J, Vaporidi K, Beitler JR, Patel BK, Yoshida T, Jaber S, Dres M, Mauri T, Bellani G, Demoule A, Brochard L, Heunks L. Clinical strategies for implementing lung and diaphragm-protective ventilation: avoiding insufficient and excessive effort. Intensive Care Med. 2020 Dec;46(12):2314-2326. doi: 10.1007/s00134-020-06288-9. Epub 2020 Nov 2.
- Background: PubMed 34115638Dzierba AL, Khalil AM, Derry KL, Madahar P, Beitler JR. Discordance Between Respiratory Drive and Sedation Depth in Critically Ill Patients Receiving Mechanical Ventilation. Crit Care Med. 2021 Dec 1;49(12):2090-2101. doi: 10.1097/CCM.0000000000005113.
- Background: PubMed 33710031Wongtangman K, Grabitz SD, Hammer M, Wachtendorf LJ, Xu X, Schaefer MS, Fassbender P, Santer P, Kassis EB, Talmor D, Eikermann M; SICU Optimal Mobilization Team (SOMT) Group. Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network. Crit Care Med. 2021 Jul 1;49(7):1137-1148. doi: 10.1097/CCM.0000000000004951.
- Background: PubMed 20015357Jackson DL, Proudfoot CW, Cann KF, Walsh TS. The incidence of sub-optimal sedation in the ICU: a systematic review. Crit Care. 2009;13(6):R204. doi: 10.1186/cc8212. Epub 2009 Dec 16.
- Background: PubMed 36239747Kassis EB, Beitler JR, Talmor D. Lung-protective sedation: moving toward a new paradigm of precision sedation. Intensive Care Med. 2023 Jan;49(1):91-94. doi: 10.1007/s00134-022-06901-z. Epub 2022 Oct 14. No abstract available.
- Background: PubMed 32204729Bertoni M, Spadaro S, Goligher EC. Monitoring Patient Respiratory Effort During Mechanical Ventilation: Lung and Diaphragm-Protective Ventilation. Crit Care. 2020 Mar 24;24(1):106. doi: 10.1186/s13054-020-2777-y.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in a publication of this study (after deidentification)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Tanuwong Viarasilpa, MD principal investigator
Division of Critical Care, Department of Medicine, Siriraj Hospital, Mahidol University
Natdanai Ketdao, MD principal investigator
Division of Critical Care, Department of Medicine, Siriraj Hospital, Mahidol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Titrating sedation targeting both optimal P0.1 and appropriate arousal level, Fentanyl and Midazolam in people with Respiratory Failure and Critical Illness, run by Siriraj Hospital at 1 site in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natdanai Ketdao, MD (+66880684998, natdke@kku.ac.th), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Successful extubation within 14 days after randomization (time frame: 14 days after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06203405, which also lists 37 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2025.