Trial Outcomes & Findings for Pilot Study on Pairing Sedation Strategies and Weaning (NCT NCT02219659)
NCT ID: NCT02219659
Last Updated: 2025-10-07
Results Overview
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).
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
90 participants
Primary outcome timeframe
Up to 28 days
Results posted on
2025-10-07
Participant Flow
12-2014 to 5/2017, ICU
Participant milestones
| Measure |
Fentanyl Push First
Fentanyl intravenous (IV) pushes are administered every 5 minutes as needed to target pain and sedation score, up to 4 doses per hour. 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.
Fentanyl Push First: 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 morn
|
Sedation Protocol Without Interruption
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
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.
|
|---|---|---|---|
|
Overall Study
STARTED
|
29
|
30
|
31
|
|
Overall Study
COMPLETED
|
27
|
28
|
31
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Fentanyl Push First
n=27 Participants
. 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.
|
Sedation Protocol Without Interruption
n=28 Participants
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
n=31 Participants
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.
|
Total
n=86 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=27 Participants
|
0 Participants
n=28 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=86 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=27 Participants
|
13 Participants
n=28 Participants
|
15 Participants
n=31 Participants
|
40 Participants
n=86 Participants
|
|
Age, Categorical
>=65 years
|
15 Participants
n=27 Participants
|
15 Participants
n=28 Participants
|
16 Participants
n=31 Participants
|
46 Participants
n=86 Participants
|
|
Age, Continuous
|
65.6 years
STANDARD_DEVIATION 15.8 • n=27 Participants
|
64.1 years
STANDARD_DEVIATION 18.4 • n=28 Participants
|
66 years
STANDARD_DEVIATION 16.4 • n=31 Participants
|
65.2 years
STANDARD_DEVIATION 18.4 • n=86 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=27 Participants
|
1 Participants
n=28 Participants
|
8 Participants
n=31 Participants
|
10 Participants
n=86 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=27 Participants
|
27 Participants
n=28 Participants
|
23 Participants
n=31 Participants
|
76 Participants
n=86 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
27 Participants
n=27 Participants
|
28 Participants
n=28 Participants
|
31 Participants
n=31 Participants
|
86 Participants
n=86 Participants
|
|
Body Mass Index (BMI) Kg/m^2
|
31.5 kg/m^2
STANDARD_DEVIATION 9.9 • n=27 Participants
|
31.2 kg/m^2
STANDARD_DEVIATION 10.1 • n=28 Participants
|
30.3 kg/m^2
STANDARD_DEVIATION 10.3 • n=31 Participants
|
31 kg/m^2
STANDARD_DEVIATION 10.1 • n=86 Participants
|
PRIMARY outcome
Timeframe: Up to 28 daysPopulation: All 3 arms were measure, and the measurement was based on total % of study days where compliant with the respective protocol.
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).
Outcome measures
| Measure |
Protocol Compliance
n=27 Participants
Feasibility outcomes and a priori-defined benchmarks: protocol compliance
|
Sedation Protocol Without Interruption
n=28 Participants
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
n=31 Participants
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
|
|---|---|---|---|
|
Study Feasibility
|
91 Percentage of study days
|
97 Percentage of study days
|
93 Percentage of study days
|
SECONDARY outcome
Timeframe: Up to 28 daysDuration of ICU stay at 28 days
Outcome measures
| Measure |
Protocol Compliance
n=27 Participants
Feasibility outcomes and a priori-defined benchmarks: protocol compliance
|
Sedation Protocol Without Interruption
n=28 Participants
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
n=31 Participants
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
|
|---|---|---|---|
|
ICU Length of Stay
|
7 Days
Interval 4.0 to 14.0
|
7 Days
Interval 3.0 to 15.0
|
8 Days
Interval 3.0 to 15.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 28 daysThis is clinical outcome and represent the number of days where patients were breathing without assistance during the study period.
Outcome measures
| Measure |
Protocol Compliance
n=27 Participants
Feasibility outcomes and a priori-defined benchmarks: protocol compliance
|
Sedation Protocol Without Interruption
n=28 Participants
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
n=31 Participants
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
|
|---|---|---|---|
|
Mechanical Ventilation Free Days
|
24 days
Interval 23.0 to 26.0
|
23.5 days
Interval 20.0 to 26.0
|
24 days
Interval 21.0 to 26.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 28 daysDuration of weaning: Time from initiation of weaning until successful extubation
Outcome measures
| Measure |
Protocol Compliance
n=27 Participants
Feasibility outcomes and a priori-defined benchmarks: protocol compliance
|
Sedation Protocol Without Interruption
n=28 Participants
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.
Sedation Protocol Without Daily Interruption: 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.
|
Sedation Protocol With Interruption
n=31 Participants
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
|
|---|---|---|---|
|
Duration of Weaning
|
2 days
Interval 1.0 to 3.0
|
2 days
Interval 1.0 to 3.0
|
2 days
Interval 1.0 to 3.0
|
Adverse Events
Fentanyl Push First
Serious events: 1 serious events
Other events: 0 other events
Deaths: 8 deaths
Sedation Protocol Without Interruption
Serious events: 0 serious events
Other events: 0 other events
Deaths: 6 deaths
Sedation Protocol With Interruption
Serious events: 1 serious events
Other events: 0 other events
Deaths: 4 deaths
Serious adverse events
| Measure |
Fentanyl Push First
n=27 participants at risk
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.
|
Sedation Protocol Without Interruption
n=28 participants at risk
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.
|
Sedation Protocol With Interruption
n=31 participants at risk
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.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Unplanned Extubation
|
3.7%
1/27 • 28 days
Unintentional extubation
|
0.00%
0/28 • 28 days
Unintentional extubation
|
3.2%
1/31 • 28 days
Unintentional extubation
|
Other adverse events
Adverse event data not reported
Additional Information
Division of Pulmonary and Critical Care
MemorialCare Long Beach
Phone: (562) 933-2000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place