Trial Outcomes & Findings for Pharmacoeconomic Consequences Of Analgesia in the Intensive Care Unit (ICU) (NCT NCT00436345)

NCT ID: NCT00436345

Last Updated: 2017-05-30

Results Overview

Time from start of mechanical ventilation until actual extubation (the process of removing a tube from the airway).

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 39 participants
• Primary outcome timeframe: Up to 38 days (912 hours)
• Results posted on: 2017-05-30

Participant Flow

Participant milestones

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Overall Study STARTED	21	18
Overall Study COMPLETED	18	18
Overall Study NOT COMPLETED	3	0

Reasons for withdrawal

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Overall Study ICU resident beyond follow-up period	3	0

Baseline Characteristics

Pharmacoeconomic Consequences Of Analgesia in the Intensive Care Unit (ICU)

Baseline characteristics by cohort

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.	Total n=39 Participants Total of all reporting groups
Age, Continuous	62.1 years STANDARD_DEVIATION 10.7 • n=5 Participants	60.2 years STANDARD_DEVIATION 14.3 • n=7 Participants	61.23 years STANDARD_DEVIATION 12.32 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized White	21 participants n=5 Participants	17 participants n=7 Participants	38 participants n=5 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Simplified acute physiology score (SAPS II) score	25.7 Points on a scale STANDARD_DEVIATION 16.7 • n=5 Participants	20.9 Points on a scale STANDARD_DEVIATION 16.1 • n=7 Participants	23.23 Points on a scale STANDARD_DEVIATION 16.30 • n=5 Participants

PRIMARY outcome

Timeframe: Up to 38 days (912 hours)

Population: Intent-to-Treat (ITT) Population: all randomised participants who had taken at least one dose of study medication

Time from start of mechanical ventilation until actual extubation (the process of removing a tube from the airway).

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Time on Mechanical Ventilation (Intent-to-Treat Population)	77 Hours (hr) Standard Error 8.31	70 Hours (hr) Standard Error 6.48

PRIMARY outcome

Timeframe: Up to 38 days (912 hours)

Population: Modified-Intent-to-Treat (mITT) Population: all randomised participants who had taken at least one dose of study medication and who had efficacy measurements

Time from start of mechanical ventilation until actual extubation.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population)	77 Hours Standard Error 8.31	70 Hours Standard Error 6.48

PRIMARY outcome

Timeframe: Up to 38 days (912 hours)

Population: Per-Protocol (PP) Population: all participants from the MITT population without any major protocol violation

Time from start of mechanical ventilation until actual extubation

Outcome measures

Measure	Remifentanil n=11 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=13 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Time on Mechanical Ventilation (Per-Protocol Population)	87 Hours Standard Error 9.47	81 Hours Standard Error 4.71

SECONDARY outcome

Timeframe: Up to 38 days (912 hours)

Population: ITT Population. Only participants with available ICU data were analyzed.

Duration of Intensive Care Unit (ICU) stay and the duration of potential stay in the ICU were measured.

Outcome measures

Measure	Remifentanil n=12 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=14 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Time in Intensive Care Unit (ICU) and Potential Stay in ICU (the Time Expected for Extubation, i.e., the Time Between Intubation and Eligibility for Extubation, According to Investigator's Decision) Duration of ICU stay	212.6 Hours Standard Deviation 163.4	208.5 Hours Standard Deviation 185.2
Duration of Time in Intensive Care Unit (ICU) and Potential Stay in ICU (the Time Expected for Extubation, i.e., the Time Between Intubation and Eligibility for Extubation, According to Investigator's Decision) Duration of potential ICU stay	211.3 Hours Standard Deviation 161.4	208.1 Hours Standard Deviation 185.1

SECONDARY outcome

Timeframe: up to 38 days (912 hours)

Population: ITT Population. Only participants with available extubation data were analyzed.

Duration of extubation was measured.

Outcome measures

Measure	Remifentanil n=13 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=12 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Extubation	0.4 hours Standard Deviation 0.5	0.7 hours Standard Deviation 0.8

SECONDARY outcome

Timeframe: up to 38 days (912 hours)

Population: ITT Population. Only participants for which data are available were analyzed.

Duration of weaning (the time from the intubation until the recovery of natural respiratory ability) was measured.

Outcome measures

Measure	Remifentanil n=19 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=14 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Weaning	0.42 hours Standard Deviation 1.0	0.26 hours Standard Deviation 0.3

SECONDARY outcome

Timeframe: Up to 10 days (240 hours)

Population: ITT Population. Only participants infused with Remifentanil were analyzed.

Data for this measure come from the infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Remifentanil Infusion (ITT Population)	67.7 Hours Standard Deviation 60.3	—

SECONDARY outcome

Timeframe: up to 10 days (240 hours)

Population: ITT Population. Only participants infused with Propofol were analyzed.

Data for this measure come from the infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil n=13 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Propofol Infusion (ITT Population)	47.6 hours Standard Deviation 41.8	86.2 hours Standard Deviation 89.4

SECONDARY outcome

Timeframe: up to 10 days (240 hours)

Population: ITT Population. Only participants infused with Sufentanil, Fentanil, and Morphine were analyzed.

Data for this measure come from the infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=8 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) Sufentanil, n=8	—	51.2 hours Standard Deviation 15.42
Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) Fentanil, n=5	—	47.5 hours Standard Deviation 40.7
Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) Morphine, n=1	—	0.03 hours Standard Deviation 0.0

SECONDARY outcome

Timeframe: Up to 10 days

Population: ITT Population. Only participants dosed with Remifentanil were analyzed.

Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Dose of Remifentanil Administered - Continuous Infusion	10.6 ug/kg/h (micrograms per kilogram per hr) Standard Deviation 7.2	—

SECONDARY outcome

Timeframe: up to 10 days

Population: ITT Population. Only participants dosed with Remifentanil were analyzed.

Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=8 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Doses of Sufentanil and Fentanil Administered - Continuous Infusion Sufentanil, n=8	—	0.2 ug/kg/h Standard Deviation 0.1
Doses of Sufentanil and Fentanil Administered - Continuous Infusion Fentanil, n=5	—	5.0 ug/kg/h Standard Deviation 7.5

SECONDARY outcome

Timeframe: Up to 10 days

Population: ITT Population. Only participants dosed with Propofol were analyzed.

Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil n=13 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Dose of Propofol Administered - Continuous Infusion	2.3 mg/kg/h (milligrams per kilogram per hr) Standard Deviation 4.0	1.8 mg/kg/h (milligrams per kilogram per hr) Standard Deviation 1.3

SECONDARY outcome

Timeframe: up to 10 days

Population: ITT Population. Only participants dosed with Morphine were analyzed.

Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=1 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Dose of Morphine Administered - Continuous Infusion	—	4.3 mg/kg/h Standard Deviation 0.0

SECONDARY outcome

Timeframe: Up to 10 days

Population: ITT Population. Only participants dosed with Propofol were analyzed.

Data from this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil n=4 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=4 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Total Dose of Propofol Administered - Bolus	1.5 mg/kg Standard Deviation 0.4	5.5 mg/kg Standard Deviation 4.5

SECONDARY outcome

Timeframe: Up to 10 days

Population: ITT Population. Only participants dosed with Fentanil were analyzed.

Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.

Outcome measures

Measure	Remifentanil Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=5 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Total Dose of Fentanil Administered - Bolus	—	5.1 ug/kg Standard Deviation 3.6

SECONDARY outcome

Timeframe: Up to 38 Days

Population: mITT Population

Data from participants in the study for which the Sedation-Agitation Scale (SAS) and Pain Intensity (PI) were recorded were analyzed. "Sedation - Agitation" was assessed, using the "Riker Sedation-Agitation Scale" (SAS), by the following 7-point scale: 7, dangerous agitation; 6, very agitated; 5, agitated; 4, calm, cooperative; 3, sedated; 2, very sedated; 1, unarousable. "Pain Intensity" was assessed by the following 6-point Pain Intensity Scale: 1, no pain; 2, mild pain; 3, moderate pain; 4, severe pain; 5 very severe pain; 6, worst possible pain.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 3	15 participants	14 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 7	2 participants	1 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 9	1 participants	0 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Extubation period	12 participants	12 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Screening period	21 participants	18 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 1	21 participants	18 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 2	18 participants	17 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 4	10 participants	11 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 5	6 participants	3 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 6	2 participants	2 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 8	1 participants	0 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Day 10	1 participants	0 participants
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale Post-extubation period	5 participants	6 participants

SECONDARY outcome

Timeframe: Up to 38 days

Population: mITT Population, according to the participants' status

"Sedation - Agitation" was assessed, using the "Riker Sedation-Agitation Scale" (SAS), by the following 7-point scale: 7, dangerous agitation; 6, very agitated; 5, agitated; 4, calm, cooperative; 3, sedated; 2, very sedated; 1, unarousable.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Sedation-Agitation From Screening Through the End of Study Screening period	3.5 Points on a scale Standard Deviation 1.0	3.7 Points on a scale Standard Deviation 1.2
Sedation-Agitation From Screening Through the End of Study Day 1	3.0 Points on a scale Standard Deviation 0.9	2.9 Points on a scale Standard Deviation 0.8
Sedation-Agitation From Screening Through the End of Study Day 3	3.1 Points on a scale Standard Deviation 0.8	3.1 Points on a scale Standard Deviation 0.6
Sedation-Agitation From Screening Through the End of Study Day 4	3.4 Points on a scale Standard Deviation 0.9	3.1 Points on a scale Standard Deviation 0.6
Sedation-Agitation From Screening Through the End of Study Day 5	3.5 Points on a scale Standard Deviation 0.4	3.1 Points on a scale Standard Deviation 1.1
Sedation-Agitation From Screening Through the End of Study Day 2	2.8 Points on a scale Standard Deviation 1.0	2.9 Points on a scale Standard Deviation 0.9
Sedation-Agitation From Screening Through the End of Study Day 6	3.9 Points on a scale Standard Deviation 0.2	2.6 Points on a scale Standard Deviation 0.6
Sedation-Agitation From Screening Through the End of Study Extubation period	3.2 Points on a scale Standard Deviation 0.7	3.6 Points on a scale Standard Deviation 0.4
Sedation-Agitation From Screening Through the End of Study Post-extubation period	3.8 Points on a scale Standard Deviation 0.8	4.0 Points on a scale Standard Deviation 0.0

SECONDARY outcome

Timeframe: Day 7

Population: mITT Population according to the participants' status

"Sedation - Agitation" was assessed, using the "Riker Sedation-Agitation Scale" (SAS), by the following 7-point scale: 7, dangerous agitation; 6, very agitated; 5, agitated; 4, calm, cooperative; 3, sedated; 2, very sedated; 1, unarousable.

Outcome measures

Measure	Remifentanil n=1 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=1 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Sedation-Agitation for Day 7	4.0 points on a scale Standard Deviation 0.0	3.3 points on a scale Standard Deviation 0.0

SECONDARY outcome

Timeframe: Days 8, 9, and 10

Population: mITT Population according to the participants' status

"Sedation - Agitation" was assessed, using the "Riker Sedation-Agitation Scale" (SAS), by the following 7-point scale: 7, dangerous agitation; 6, very agitated; 5, agitated; 4, calm, cooperative; 3, sedated; 2, very sedated; 1, unarousable.

Outcome measures

Measure	Remifentanil n=1 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Sedation-Agitation From Day 8 to Day 10 Day 8	4.0 points on a scale Standard Deviation 0.0	—
Sedation-Agitation From Day 8 to Day 10 Day 9	3.3 points on a scale Standard Deviation 0.0	—
Sedation-Agitation From Day 8 to Day 10 Day 10	3.6 points on a scale Standard Deviation 0.0	—

SECONDARY outcome

Timeframe: Up to 38 days

Population: mITT Population

Participants in the study for which BIS were evaluated. The BIS monitor provides a single dimensionless number, the BIS value, which ranges from 0 to 100. A BIS value of 0 equals electroencephalogram silence, near 100 is the expected value in a fully awake adult, and between 40 and 60 indicates a level for general anaesthesia.

Outcome measures

Measure	Remifentanil n=5 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 2	4 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Screening period	3 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 1	4 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 3	5 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 4	4 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 5	1 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 6	0 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 7	0 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 8	0 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 9	0 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Day 10	0 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Extubation period	2 participants	—
Number of Participants Analyzed for BIS (Bispectral Index Scale) Post-extubation period	2 participants	—

SECONDARY outcome

Timeframe: Screening through End of Study, up to 38 days

Population: mITT Population. Due to the nonmandatory nature of BIS measure in the clinical practice, some participants did not have all the measures for all days in which they were in the study.

The BIS monitor provides a single dimensionless number, the BIS value, which ranges from 0 to 100. A BIS value of 0 equals electroencephalogram silence, near 100 is the expected value in a fully awake adult, and between 40 and 60 indicates a level for general anaesthesia.

Outcome measures

Measure	Remifentanil n=5 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Bispectral Index (BIS) Day 2 (n = 4, 0)	45.6 Points on a scale Standard Deviation 16.8	—
Bispectral Index (BIS) Day 3 (n = 5, 0)	45.8 Points on a scale Standard Deviation 17.5	—
Bispectral Index (BIS) Screening period (n = 3, 0)	38.0 Points on a scale Standard Deviation 4.6	—
Bispectral Index (BIS) Day 1 (n = 4, 0)	47.3 Points on a scale Standard Deviation 18.3	—
Bispectral Index (BIS) Day 4 (n = 4, 0)	49.7 Points on a scale Standard Deviation 13.3	—

SECONDARY outcome

Timeframe: Day 5

Population: mITT Population. At Day 5, only one participant remained in the study; the others were already extubated.

The BIS monitor provides a single dimensionless number, the BIS value, which ranges from 0 to 100. A BIS value of 0 equals electroencephalogram silence, near 100 is the expected value in a fully awake adult, and between 40 and 60 indicates a level for general anaesthesia.

Outcome measures

Measure	Remifentanil n=1 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Bispectral Index (BIS) for Day 5	52.7 points on a scale Standard Deviation 0.0	—

SECONDARY outcome

Timeframe: up to 38 days

Population: mITT Population. The BIS value was recorded only for 2 participants, in the extubation and post-extubation periods.

The BIS monitor provides a single dimensionless number, the BIS value, which ranges from 0 to 100. A BIS value of 0 equals electroencephalogram silence, near 100 is the expected value in a fully awake adult, and between 40 and 60 indicates a level for general anaesthesia.

Outcome measures

Measure	Remifentanil n=2 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Bispectral Index (BIS) for Extubation Period and Post-Extubation Period Extubation period	70.0 points on a scale Standard Deviation 0.0	—
Bispectral Index (BIS) for Extubation Period and Post-Extubation Period Post-Extubation period	71.8 points on a scale Standard Deviation 1.1	—

SECONDARY outcome

Timeframe: Up to 38 days

Population: ITT Population, according to the participants' status. Participants remained in the study until they could be extubated; thus, the number of participants analyzed may vary by day.

"Pain Intensity" was assessed by the following 6-point Pain Intensity Scale: 1, no pain; 2, mild pain; 3, moderate pain; 4, severe pain; 5 very severe pain; 6, worst possible pain.

Outcome measures

Measure	Remifentanil n=21 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 Participants The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Pain Intensity (PI) Day 3, n=15, 14	1.2 Points on a scale Standard Deviation 0.4	1.1 Points on a scale Standard Deviation 0.3
Pain Intensity (PI) Day 4, n=10, 11	1.2 Points on a scale Standard Deviation 0.4	1.0 Points on a scale Standard Deviation 0.1
Pain Intensity (PI) Day 6, n=2, 2	1.0 Points on a scale Standard Deviation 0.0	1.0 Points on a scale Standard Deviation 0.0
Pain Intensity (PI) Day 7, n=2, 1	1.0 Points on a scale Standard Deviation 0.0	1.0 Points on a scale Standard Deviation 0.0
Pain Intensity (PI) Screening period, n=21, 18	1.3 Points on a scale Standard Deviation 0.8	1.2 Points on a scale Standard Deviation 0.5
Pain Intensity (PI) Day 1, n=21, 18	1.3 Points on a scale Standard Deviation 0.5	1.1 Points on a scale Standard Deviation 0.2
Pain Intensity (PI) Day 2, n=18, 17	1.2 Points on a scale Standard Deviation 0.4	1.1 Points on a scale Standard Deviation 0.2
Pain Intensity (PI) Day 5, n=6, 3	1.3 Points on a scale Standard Deviation 0.7	1.0 Points on a scale Standard Deviation 0.0
Pain Intensity (PI) Extubation period, n=12, 12	1.4 Points on a scale Standard Deviation 0.8	1.4 Points on a scale Standard Deviation 0.6
Pain Intensity (PI) Post-extubation period, n=5, 6	2.0 Points on a scale Standard Deviation 1.0	1.3 Points on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: Days 8, 9, and 10

Population: mITT Population. Participants remained in the study until they could be extubated; thus, the number of participants analyzed may vary by day.

"Pain Intensity" was assessed by the following 6-point Pain Intensity Scale: 1, no pain; 2, mild pain; 3, moderate pain; 4, severe pain; 5 very severe pain; 6, worst possible pain.

Outcome measures

Measure	Remifentanil n=1 Participants Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Pain Intensity From Day 8 to Day 10 Day 8	1.0 points on a scale Standard Deviation 0.0	—
Pain Intensity From Day 8 to Day 10 Day 9	1.0 points on a scale Standard Deviation 0.0	—
Pain Intensity From Day 8 to Day 10 Day 10	1.0 points on a scale Standard Deviation 0.0	—

Adverse Events

Remifentanil

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Propofol

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Remifentanil n=21 participants at risk Infusion started between 6 and 9 ug/kg/h (micrograms per kilogram per hour), and titrated in 1.5 ug/kg/h increments at 5-10 minute intervals to achieve a level of adequate sedation based on investigator clinical judgement. The maximum dose rate was 45 ug/kg/h. Once the remifentanil infusion rate reached 12 ug/kg/h, the sedative infusion (propofol) could be administered if level of sedation was not adequate.	Propofol n=18 participants at risk The administration of propofol combined with an opioid (fentanyl, sufentanil, morphine, or other) as required to maintain adequate analgesia/sedation and stable haemodynamics was performed according to routine clinical practice for the investigational site, and in accordance with standard clinical protocols.
Cardiac disorders Bradycardia	0.00% 0/21	5.6% 1/18
Gastrointestinal disorders Ascites	4.8% 1/21	0.00% 0/18
Respiratory, thoracic and mediastinal disorders Apnoea	9.5% 2/21	0.00% 0/18
Respiratory, thoracic and mediastinal disorders Respiratory depression	4.8% 1/21	0.00% 0/18
Respiratory, thoracic and mediastinal disorders Respiratory failure	4.8% 1/21	0.00% 0/18
Vascular disorders Hypertension	23.8% 5/21	5.6% 1/18
Vascular disorders Hypotension	9.5% 2/21	0.00% 0/18
Skin and subcutaneous tissue disorders Oedema at surgical site	0.00% 0/21	5.6% 1/18

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER