Acute Respiratory FailureNCT02219659
Pilot Study on Pairing Sedation Strategies and Weaning
A study testing Sedation Protocol with Daily Interruption, Sedation Protocol Without Daily Interruption and Fentanyl Push First in people with Acute Respiratory Failure, run by MemorialCare Health System at 1 site in United States.
Trial summary
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Failure
- What is being tested?
- Sedation Protocol with Daily Interruption, Sedation Protocol Without Daily Interruption and Fentanyl Push First
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to 18 May 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- ≥ 18 years of age
- Mechanically ventilated with an expected duration of MV ≥ 48 hours
- ICU team has initiated continuous sedative and/or /analgesic infusions
Who cannot join
- Admission after resuscitation from cardiac arrest
- Admission with traumatic brain injury or another acute neurologic event (e,g. stroke, uncontrolled seizures).
- History of severe dementia
- Admission because of acute alcohol withdrawal or acute drug intoxication
- Administration of more than 24 hours of continuous sedation
- Allergy to fentanyl, midazolam, and/or propofol
- Lack of informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Long Beach Memorial Medical Center
Long Beach, California, 90806
About this study
Official title: Comparing Strategies of Pairing Sedation and Weaning Protocols on Outcomes of Mechanical Ventilation: A Pilot Study
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
Read the detailed description
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
A significant proportion of patients admitted to the intensive care unit (ICU) require mechanical ventilation (MV). To maintain comfort and facilitate quality care, large quantities of sedatives and analgesics are often administered either by continuous infusion, with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics. Three validated sedation strategies are currently available. A recently published study ( trial has shown that instituting protocol-directed sedation in patients requiring continuous infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial) evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a Danish study by Strom et al. investigated whether an analgesia-first approach to patient comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV sedation for short periods only when acute agitation was present, would be superior to a protocol similar to the ABC trial. While the three above mentioned approaches are accepted and currently implemented in the critical care community there is no comparative study or evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing weaning readiness with each of these strategies. It is possible that a SAT strategy, where sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a strategy in patients managed with a sedation protocol where intravenous sedative and analgesic therapy is regularly titrated to maintain patients in a lightly sedated state. Moreover, it remains unclear whether analgesia-first strategy (AFS) is feasible and if there are advantages of AFS (Fentanyl push first interventions) over either an SAT or sedation protocol strategy in terms of the time it takes to wean patients from MV or ICU length of stay. However, it is noteworthy to mention that the analgesia-first strategy was associated with more delirium episodes, which were attributed to the ability to assess for it in a more awake patient. However, comparing delirium occurrence in studies with different sedation goals and methodologies may be inaccurate.
The investigators therefore propose a three-arm, randomized clinical trial. This pilot study will measure feasibility for the implementation of analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
- Conditions
- Acute Respiratory Failure
- Being tested
- Sedation Protocol with Daily Interruption, Sedation Protocol Without Daily Interruption, Fentanyl Push First
- Keywords
- sedation strategy, mechanical ventilation, ventilator weaning
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sedation Protocol with Daily InterruptionDrug
Also called fentanyl, midazolam
Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
Sedation Protocol Without Daily InterruptionDrug
Also called fentanyl, midazolam
Continuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning.
Fentanyl Push FirstDrug
Also called fentanyl, propofol
Fentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs).
| Study group | Role | What they receive |
|---|---|---|
| Sedation protocol with interruption | Active comparator | Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed. Receives: Drug: Sedation Protocol with Daily Interruption |
| Sedation protocol without Interruption | Active comparator | Continuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen. Receives: Drug: Sedation Protocol Without Daily Interruption |
| Fentanyl push first | Active comparator | This arm attempts to manage patient's pain and agitation with analgesia first. Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours. Receives: Drug: Fentanyl Push First |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study Feasibility
Study feasibility for all 3 Arms/Groups (i.e., "Fentanyl Push First", "Sedation Protocol Without Interruption", and "Sedation Protocol with Interruption") being greater than or equal to 80% and protocol feasibility was based on protocol compliance (total percentage of study days participants were compliant with protocol).
Measured: Up to 28 days
Secondary outcomes (1)
ICU Length of Stay
Duration of ICU stay at 28 days
Measured: 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 posted19 Aug 2014 (estimated)
- Study startDec 2014
- Primary completionMay 2017
- Study completion18 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute 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
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- MemorialCare Health System
- Sponsor type
- University, hospital or other
- Collaborators
- Memorial Medical Center Foundation
- Responsible party
- Sponsor
- Investigators
- Maged Tanios, MD, MPH, Principal investigator, Long Beach Memorial Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02219659
- Sponsor's protocol ID
- 25613
- Status last verified
- Sep 2025
- First submitted
- 20 Feb 2014
- Last updated
- 7 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparing Strategies of Pairing Sedation and Weaning Protocols on Outcomes of Mechanical Ventilation: A Pilot Study
- ClinicalTrials.gov ID
- NCT02219659
- Acronym / sponsor ID
- 25613
- Conditions
- Acute Respiratory Failure
- Keywords
- sedation strategy, mechanical ventilation, ventilator weaning
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- MemorialCare Health SystemUniversity, hospital or other
- Collaborators
- Memorial Medical Center Foundation
- Study start
- Dec 2014
- Primary completion
- May 2017 (actual)
- Study completion
- 18 May 2018 (actual)
- First posted
- 19 Aug 2014 (estimated)
- Results
- Posted 14 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
Detailed description
A three-arm, randomized, pilot study, to assess the feasibility for the analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
A significant proportion of patients admitted to the intensive care unit (ICU) require mechanical ventilation (MV). To maintain comfort and facilitate quality care, large quantities of sedatives and analgesics are often administered either by continuous infusion, with or without daily interruption (DI) of sedation, or as intermittent doses of analgesics. Three validated sedation strategies are currently available. A recently published study ( trial has shown that instituting protocol-directed sedation in patients requiring continuous infusion of sedatives and analgesics, whether or not daily interruption (DI) of the sedative occurs, will improve MV outcomes, specifically the duration of MV. Girard et al performed a randomized, multicenter, clinical trial (ABC- Awakening and Breathing Controlled trial) evaluating the pairing of a spontaneous awakening trial (SAT) with an SBT. Most recently, a Danish study by Strom et al. investigated whether an analgesia-first approach to patient comfort that consisted of intermittent doses of intravenous opioids, and the initiation of IV sedation for short periods only when acute agitation was present, would be superior to a protocol similar to the ABC trial. While the three above mentioned approaches are accepted and currently implemented in the critical care community there is no comparative study or evaluation on the optimal timing to conduct a spontaneous breathing trial (SBT) for assessing weaning readiness with each of these strategies. It is possible that a SAT strategy, where sedative and opioid infusions are interrupted, may lead to more agitation and anxiety than a strategy in patients managed with a sedation protocol where intravenous sedative and analgesic therapy is regularly titrated to maintain patients in a lightly sedated state. Moreover, it remains unclear whether analgesia-first strategy (AFS) is feasible and if there are advantages of AFS (Fentanyl push first interventions) over either an SAT or sedation protocol strategy in terms of the time it takes to wean patients from MV or ICU length of stay. However, it is noteworthy to mention that the analgesia-first strategy was associated with more delirium episodes, which were attributed to the ability to assess for it in a more awake patient. However, comparing delirium occurrence in studies with different sedation goals and methodologies may be inaccurate.
The investigators therefore propose a three-arm, randomized clinical trial. This pilot study will measure feasibility for the implementation of analgesia-first sedation (AFS) study arm/intervention (Fentanyl push first). The study will assess additional outcomes for all three (3) validated strategies for sedation and pain management.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sedation protocol with interruption | Active comparator | Drug: Sedation Protocol with Daily InterruptionContinuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Every morning both drugs are stopped (Daily Interruption) and patient's wakefulness is assessed per protocol. If patient's pain and RASS score stays within the target, both drugs are kept off. If patient shows any signs and symptoms of pain or agitation (described in the study protocol), both drugs are restarted at a half dose of the previous dose and titrated to target pain and RASS score. Every morning both drugs are stopped and when patient is awake and met the SBT safety screen, 120-min continuous positive airway pressure (CPAP) trial is performed. |
| Sedation protocol without Interruption | Active comparator | Drug: Sedation Protocol Without Daily InterruptionContinuous infusion of fentanyl and midazolam is started per protocol. Both drugs are titrated to target pain score (0 to 3) using Critical Care Pain Observation Tool (CPOT) and target sedation score (0 to -3) using Richmond Agitation Sedation Scale (RASS). Daily interruption of fentanyl and midazolam is not performed. Every morning 120-min CPAP trial is performed as long as the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen. |
| Fentanyl push first | Active comparator | Drug: Fentanyl Push FirstThis arm attempts to manage patient's pain and agitation with analgesia first. Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. Every morning 120-min CPAP trial is performed as long as patient's RASS score is 0 to -2 and patient passes the SBT safety screen. If fentanyl IV push doses alone cannot manage patient's pain and agitation (could not reach the target score), notify the study team. Fentanyl infusion is started and titrated to target pain and sedation score up to 6 hours. If fentanyl infusion is titrated up twice consecutively and target pain and sedation score are not met, notify the study team. Propofol infusion is started and titrated to target RASS score up to 6 hours. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ≥ 18 years of age
- Mechanically ventilated with an expected duration of MV ≥ 48 hours
- ICU team has initiated continuous sedative and/or /analgesic infusions
Key exclusion criteria (7 listed)
- Admission after resuscitation from cardiac arrest
- Admission with traumatic brain injury or another acute neurologic event (e,g. stroke, uncontrolled seizures).
- History of severe dementia
- Admission because of acute alcohol withdrawal or acute drug intoxication
- Administration of more than 24 hours of continuous sedation
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 |
|---|---|---|
| Sedation Protocol with Daily InterruptionAlso: fentanyl, midazolamContinuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning both infusions are stopped and when the patient is awake and met the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning. | Drug | Sedation protocol with interruption |
| Sedation Protocol Without Daily InterruptionAlso: fentanyl, midazolamContinuous infusion of fentanyl and midazolam is started and titrated to target pain and RASS score: Fentanyl started at 25 mcg/hr titrated by 25 mcg/hr every 30 minutes to goal pain score; Midazolam started at 1 mg/hr titrated by 1 mg/hr every hour to goal RASS score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when the patient's RASS score is 0 to -2 and the patient passes the SBT safety screen, 120-min CPAP trial is performed. If the patient meets the CPAP passing criteria, arterial blood gas (ABG) is done and the patient is placed back to the previous ventilator setting. ABG result is notified to the physician for determination for extubation. If the patient does not pass the CPAP trial it is repeated next morning. | Drug | Sedation protocol without Interruption |
| Fentanyl Push FirstAlso: fentanyl, propofolFentanyl 25 mcg intravenous push (IVP) every 5 min up to 4 doses hourly as needed to target pain score for the study design duration (28 days) or for the duration of mechanical ventilation. Every morning when patient's RASS is 0 to -2 and passes the SBT safety screen, 120-min CPAP trial is performed. If patient meets CPAP passing criteria, the physician will be notified for determination of extubation. If patient does not pass, it is repeated next morning. If target RASS is not achieved with fentanyl IV push alone, study team is notified and fentanyl infusion at 50 mcg/hr titrated by 25 mcg/hr every 30 min to target pain score (max 6 hrs). If target RASS score is not achieved with the fentanyl IV, propofol infusion is started at 5 mcg/kg/hr titrated by 5 mcg/kg/hr every 15 min to target RASS score (max 6 hrs). | Drug | Fentanyl push first |
Primary outcome
Study Feasibility
Time frame: Up to 28 days
Study feasibility for all 3 Arms/Groups (i.e., "Fentanyl Push First", "Sedation Protocol Without Interruption", and "Sedation Protocol with Interruption") being greater than or equal to 80% and protocol feasibility was based on protocol compliance (total percentage of study days participants were compliant with protocol).
1 secondary outcome
ICU Length of Stay
Time frame: Up to 28 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Maged Tanios, MD, MPH principal investigator
Long Beach Memorial Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sedation Protocol with Daily Interruption, Sedation Protocol Without Daily Interruption and Fentanyl Push First in people with Acute Respiratory Failure, run by MemorialCare Health System at 1 site in United States.
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 7 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: finished, as of the sponsor's last update on 7 Oct 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 United States. 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?
Yes. Results are posted in the registry (first posted 14 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Study Feasibility (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Oct 2025.