Analgesia
Conditions
Keywords
analgesia, Mechanical ventilation, pharmaco-economic, ICU
Brief summary
This study will be a multicentre randomized, open-label, phase IIIb study. This study will evaluate two different techniques of sedation: an analgesia based regimen with remifentanil versus a conventional sedation based regimen using propofol in subjects that require mechanical ventilation for at least 2 days in the ICU. The conventional sedation based regimen will consist of propofol combined with an opioid according to routine clinical practice (morphine, fentanyl, sufentanil or other as required) . The analgesia based regimen will consist of remifentanil, with propofol added on if required.
Interventions
DRUGRemifentanil
analgesia in medical and post-surgical Intensive Care Unit subjects requiring mechanical ventilation
DRUGPropofol
conventional sedation in medical and post-surgical Intensive Care Unit subjects requiring mechanical
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Medical and post-surgical patients admitted to ICU and requiring mechanical ventilation. * Intubated subjects expected to require mechanical ventilation for longer than 48 hours after starting the study drug. * Subjects requiring both analgesia and sedation with a regimen comprising a hypnotic agent and an opioid.
Exclusion criteria
* Diagnosis: cardiopulmonary resuscitation (CPR) in the previous 24 hours or expecting to require major surgery within the next three days * Subject who, in the judgement of the investigator, has a life expectancy of 2 days or refrained or refuses full life support, which would limit the care provided * Concurrent medications: * Requires or is likely to require neuromuscular blocking agents by continuous infusion to facilitate mechanical ventilation * Has or is likely to receive an epidural block during the treatment period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Time on Mechanical Ventilation (Intent-to-Treat Population) | Up to 38 days (912 hours) | Time from start of mechanical ventilation until actual extubation (the process of removing a tube from the airway). |
| Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population) | Up to 38 days (912 hours) | Time from start of mechanical ventilation until actual extubation. |
| Duration of Time on Mechanical Ventilation (Per-Protocol Population) | Up to 38 days (912 hours) | Time from start of mechanical ventilation until actual extubation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Remifentanil Infusion (ITT Population) | Up to 10 days (240 hours) | 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. |
| Duration of Propofol Infusion (ITT Population) | up to 10 days (240 hours) | 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. |
| Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) | up to 10 days (240 hours) | 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. |
| Dose of Remifentanil Administered - Continuous Infusion | Up to 10 days | Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| Doses of Sufentanil and Fentanil Administered - Continuous Infusion | up to 10 days | Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| Dose of Propofol Administered - Continuous Infusion | Up to 10 days | Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| Dose of Morphine Administered - Continuous Infusion | up to 10 days | Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| Total Dose of Propofol Administered - Bolus | Up to 10 days | Data from this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| Total Dose of Fentanil Administered - Bolus | Up to 10 days | Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system. |
| 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) | Up to 38 days (912 hours) | Duration of Intensive Care Unit (ICU) stay and the duration of potential stay in the ICU were measured. |
| Sedation-Agitation From Screening Through the End of Study | Up to 38 days | 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. |
| Sedation-Agitation for Day 7 | Day 7 | 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. |
| Sedation-Agitation From Day 8 to Day 10 | Days 8, 9, and 10 | 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. |
| Number of Participants Analyzed for BIS (Bispectral Index Scale) | Up to 38 days | 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. |
| Bispectral Index (BIS) | Screening through End of Study, up to 38 days | 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. |
| Bispectral Index (BIS) for Day 5 | Day 5 | 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. |
| Bispectral Index (BIS) for Extubation Period and Post-Extubation Period | up to 38 days | 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. |
| Pain Intensity (PI) | Up to 38 days | 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. |
| Pain Intensity From Day 8 to Day 10 | Days 8, 9, and 10 | 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. |
| Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Up to 38 Days | 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. |
| Duration of Extubation | up to 38 days (912 hours) | Duration of extubation was measured. |
| Duration of Weaning | up to 38 days (912 hours) | Duration of weaning (the time from the intubation until the recovery of natural respiratory ability) was measured. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 21 |
| 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. | 18 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | ICU resident beyond follow-up period | 3 | 0 |
Baseline characteristics
| Characteristic | Remifentanil | Propofol | Total |
|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 10.7 | 60.2 years STANDARD_DEVIATION 14.3 | 61.23 years STANDARD_DEVIATION 12.32 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 21 participants | 17 participants | 38 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 10 Participants | 11 Participants | 21 Participants |
| Simplified acute physiology score (SAPS II) score | 25.7 Points on a scale STANDARD_DEVIATION 16.7 | 20.9 Points on a scale STANDARD_DEVIATION 16.1 | 23.23 Points on a scale STANDARD_DEVIATION 16.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / — | 3 / — |
| serious Total, serious adverse events | 0 / 21 | 0 / 18 |
Outcome results
Primary
Duration of Time on Mechanical Ventilation (Intent-to-Treat Population)
Time from start of mechanical ventilation until actual extubation (the process of removing a tube from the airway).
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Time on Mechanical Ventilation (Intent-to-Treat Population) | 77 Hours (hr) | Standard Error 8.31 |
| Propofol | Duration of Time on Mechanical Ventilation (Intent-to-Treat Population) | 70 Hours (hr) | Standard Error 6.48 |
Primary
Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population)
Time from start of mechanical ventilation until actual extubation.
Time frame: 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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population) | 77 Hours | Standard Error 8.31 |
| Propofol | Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population) | 70 Hours | Standard Error 6.48 |
Primary
Duration of Time on Mechanical Ventilation (Per-Protocol Population)
Time from start of mechanical ventilation until actual extubation
Time frame: Up to 38 days (912 hours)
Population: Per-Protocol (PP) Population: all participants from the MITT population without any major protocol violation
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Time on Mechanical Ventilation (Per-Protocol Population) | 87 Hours | Standard Error 9.47 |
| Propofol | Duration of Time on Mechanical Ventilation (Per-Protocol Population) | 81 Hours | Standard Error 4.71 |
Secondary
Bispectral Index (BIS)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Bispectral Index (BIS) | Screening period (n = 3, 0) | 38.0 Points on a scale | Standard Deviation 4.6 |
| Remifentanil | Bispectral Index (BIS) | Day 1 (n = 4, 0) | 47.3 Points on a scale | Standard Deviation 18.3 |
| Remifentanil | Bispectral Index (BIS) | Day 2 (n = 4, 0) | 45.6 Points on a scale | Standard Deviation 16.8 |
| Remifentanil | Bispectral Index (BIS) | Day 3 (n = 5, 0) | 45.8 Points on a scale | Standard Deviation 17.5 |
| Remifentanil | Bispectral Index (BIS) | Day 4 (n = 4, 0) | 49.7 Points on a scale | Standard Deviation 13.3 |
Secondary
Bispectral Index (BIS) for Day 5
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.
Time frame: Day 5
Population: mITT Population. At Day 5, only one participant remained in the study; the others were already extubated.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Bispectral Index (BIS) for Day 5 | 52.7 points on a scale | Standard Deviation 0 |
Secondary
Bispectral Index (BIS) for Extubation Period and Post-Extubation Period
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.
Time frame: up to 38 days
Population: mITT Population. The BIS value was recorded only for 2 participants, in the extubation and post-extubation periods.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Bispectral Index (BIS) for Extubation Period and Post-Extubation Period | Extubation period | 70.0 points on a scale | Standard Deviation 0 |
| Remifentanil | Bispectral Index (BIS) for Extubation Period and Post-Extubation Period | Post-Extubation period | 71.8 points on a scale | Standard Deviation 1.1 |
Secondary
Dose of Morphine Administered - Continuous Infusion
Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: up to 10 days
Population: ITT Population. Only participants dosed with Morphine were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propofol | Dose of Morphine Administered - Continuous Infusion | 4.3 mg/kg/h | Standard Deviation 0 |
Secondary
Dose of Propofol Administered - Continuous Infusion
Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: Up to 10 days
Population: ITT Population. Only participants dosed with Propofol were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Dose of Propofol Administered - Continuous Infusion | 2.3 mg/kg/h (milligrams per kilogram per hr) | Standard Deviation 4 |
| Propofol | Dose of Propofol Administered - Continuous Infusion | 1.8 mg/kg/h (milligrams per kilogram per hr) | Standard Deviation 1.3 |
Secondary
Dose of Remifentanil Administered - Continuous Infusion
Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: Up to 10 days
Population: ITT Population. Only participants dosed with Remifentanil were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Dose of Remifentanil Administered - Continuous Infusion | 10.6 ug/kg/h (micrograms per kilogram per hr) | Standard Deviation 7.2 |
Secondary
Doses of Sufentanil and Fentanil Administered - Continuous Infusion
Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: up to 10 days
Population: ITT Population. Only participants dosed with Remifentanil were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propofol | Doses of Sufentanil and Fentanil Administered - Continuous Infusion | Sufentanil, n=8 | 0.2 ug/kg/h | Standard Deviation 0.1 |
| Propofol | Doses of Sufentanil and Fentanil Administered - Continuous Infusion | Fentanil, n=5 | 5.0 ug/kg/h | Standard Deviation 7.5 |
Secondary
Duration of Extubation
Duration of extubation was measured.
Time frame: up to 38 days (912 hours)
Population: ITT Population. Only participants with available extubation data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Extubation | 0.4 hours | Standard Deviation 0.5 |
| Propofol | Duration of Extubation | 0.7 hours | Standard Deviation 0.8 |
Secondary
Duration of Propofol Infusion (ITT Population)
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.
Time frame: up to 10 days (240 hours)
Population: ITT Population. Only participants infused with Propofol were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Propofol Infusion (ITT Population) | 47.6 hours | Standard Deviation 41.8 |
| Propofol | Duration of Propofol Infusion (ITT Population) | 86.2 hours | Standard Deviation 89.4 |
Secondary
Duration of Remifentanil Infusion (ITT Population)
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.
Time frame: Up to 10 days (240 hours)
Population: ITT Population. Only participants infused with Remifentanil were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Remifentanil Infusion (ITT Population) | 67.7 Hours | Standard Deviation 60.3 |
Secondary
Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population)
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.
Time frame: up to 10 days (240 hours)
Population: ITT Population. Only participants infused with Sufentanil, Fentanil, and Morphine were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propofol | Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) | Sufentanil, n=8 | 51.2 hours | Standard Deviation 15.42 |
| Propofol | Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) | Fentanil, n=5 | 47.5 hours | Standard Deviation 40.7 |
| Propofol | Duration of Sufentanil, Fentanil, and Morphine Infusion (ITT Population) | Morphine, n=1 | 0.03 hours | Standard Deviation 0 |
Secondary
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 Intensive Care Unit (ICU) stay and the duration of potential stay in the ICU were measured.
Time frame: Up to 38 days (912 hours)
Population: ITT Population. Only participants with available ICU data were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | 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 |
| Remifentanil | 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 |
| Propofol | 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 | 208.1 Hours | Standard Deviation 185.1 |
| Propofol | 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 | 208.5 Hours | Standard Deviation 185.2 |
Secondary
Duration of Weaning
Duration of weaning (the time from the intubation until the recovery of natural respiratory ability) was measured.
Time frame: up to 38 days (912 hours)
Population: ITT Population. Only participants for which data are available were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Duration of Weaning | 0.42 hours | Standard Deviation 1 |
| Propofol | Duration of Weaning | 0.26 hours | Standard Deviation 0.3 |
Secondary
Number of Participants Analyzed for BIS (Bispectral Index Scale)
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.
Time frame: Up to 38 days
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Screening period | 3 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 1 | 4 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 2 | 4 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 3 | 5 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 4 | 4 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 5 | 1 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 6 | 0 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 7 | 0 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 8 | 0 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 9 | 0 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Day 10 | 0 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Extubation period | 2 participants |
| Remifentanil | Number of Participants Analyzed for BIS (Bispectral Index Scale) | Post-extubation period | 2 participants |
Secondary
Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale
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.
Time frame: Up to 38 Days
Population: mITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Post-extubation period | 5 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Screening period | 21 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 1 | 21 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 2 | 18 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 3 | 15 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 4 | 10 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 5 | 6 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 6 | 2 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 7 | 2 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 8 | 1 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 9 | 1 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 10 | 1 participants |
| Remifentanil | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Extubation period | 12 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 9 | 0 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 6 | 2 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Screening period | 18 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Extubation period | 12 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 1 | 18 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 7 | 1 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 2 | 17 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 10 | 0 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 3 | 14 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 8 | 0 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 4 | 11 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Post-extubation period | 6 participants |
| Propofol | Number of Participants Analyzed for Sedation - Agitation Scale (SAS) and Pain Intensity (PI) Scale | Day 5 | 3 participants |
Secondary
Pain Intensity From Day 8 to Day 10
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Pain Intensity From Day 8 to Day 10 | Day 8 | 1.0 points on a scale | Standard Deviation 0 |
| Remifentanil | Pain Intensity From Day 8 to Day 10 | Day 9 | 1.0 points on a scale | Standard Deviation 0 |
| Remifentanil | Pain Intensity From Day 8 to Day 10 | Day 10 | 1.0 points on a scale | Standard Deviation 0 |
Secondary
Pain Intensity (PI)
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Pain Intensity (PI) | Day 5, n=6, 3 | 1.3 Points on a scale | Standard Deviation 0.7 |
| Remifentanil | Pain Intensity (PI) | Day 1, n=21, 18 | 1.3 Points on a scale | Standard Deviation 0.5 |
| Remifentanil | Pain Intensity (PI) | Day 6, n=2, 2 | 1.0 Points on a scale | Standard Deviation 0 |
| Remifentanil | Pain Intensity (PI) | Screening period, n=21, 18 | 1.3 Points on a scale | Standard Deviation 0.8 |
| Remifentanil | Pain Intensity (PI) | Day 7, n=2, 1 | 1.0 Points on a scale | Standard Deviation 0 |
| Remifentanil | Pain Intensity (PI) | Day 2, n=18, 17 | 1.2 Points on a scale | Standard Deviation 0.4 |
| Remifentanil | Pain Intensity (PI) | Extubation period, n=12, 12 | 1.4 Points on a scale | Standard Deviation 0.8 |
| Remifentanil | Pain Intensity (PI) | Day 4, n=10, 11 | 1.2 Points on a scale | Standard Deviation 0.4 |
| Remifentanil | Pain Intensity (PI) | Post-extubation period, n=5, 6 | 2.0 Points on a scale | Standard Deviation 1 |
| Remifentanil | Pain Intensity (PI) | Day 3, n=15, 14 | 1.2 Points on a scale | Standard Deviation 0.4 |
| Propofol | Pain Intensity (PI) | Post-extubation period, n=5, 6 | 1.3 Points on a scale | Standard Deviation 0.5 |
| Propofol | Pain Intensity (PI) | Day 4, n=10, 11 | 1.0 Points on a scale | Standard Deviation 0.1 |
| Propofol | Pain Intensity (PI) | Screening period, n=21, 18 | 1.2 Points on a scale | Standard Deviation 0.5 |
| Propofol | Pain Intensity (PI) | Day 1, n=21, 18 | 1.1 Points on a scale | Standard Deviation 0.2 |
| Propofol | Pain Intensity (PI) | Day 2, n=18, 17 | 1.1 Points on a scale | Standard Deviation 0.2 |
| Propofol | Pain Intensity (PI) | Day 5, n=6, 3 | 1.0 Points on a scale | Standard Deviation 0 |
| Propofol | Pain Intensity (PI) | Day 6, n=2, 2 | 1.0 Points on a scale | Standard Deviation 0 |
| Propofol | Pain Intensity (PI) | Day 7, n=2, 1 | 1.0 Points on a scale | Standard Deviation 0 |
| Propofol | Pain Intensity (PI) | Extubation period, n=12, 12 | 1.4 Points on a scale | Standard Deviation 0.6 |
| Propofol | Pain Intensity (PI) | Day 3, n=15, 14 | 1.1 Points on a scale | Standard Deviation 0.3 |
Secondary
Sedation-Agitation for Day 7
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.
Time frame: Day 7
Population: mITT Population according to the participants' status
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Sedation-Agitation for Day 7 | 4.0 points on a scale | Standard Deviation 0 |
| Propofol | Sedation-Agitation for Day 7 | 3.3 points on a scale | Standard Deviation 0 |
Secondary
Sedation-Agitation From Day 8 to Day 10
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.
Time frame: Days 8, 9, and 10
Population: mITT Population according to the participants' status
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Sedation-Agitation From Day 8 to Day 10 | Day 8 | 4.0 points on a scale | Standard Deviation 0 |
| Remifentanil | Sedation-Agitation From Day 8 to Day 10 | Day 9 | 3.3 points on a scale | Standard Deviation 0 |
| Remifentanil | Sedation-Agitation From Day 8 to Day 10 | Day 10 | 3.6 points on a scale | Standard Deviation 0 |
Secondary
Sedation-Agitation From Screening Through the End of Study
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.
Time frame: Up to 38 days
Population: mITT Population, according to the participants' status
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Screening period | 3.5 Points on a scale | Standard Deviation 1 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 1 | 3.0 Points on a scale | Standard Deviation 0.9 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 2 | 2.8 Points on a scale | Standard Deviation 1 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 3 | 3.1 Points on a scale | Standard Deviation 0.8 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 4 | 3.4 Points on a scale | Standard Deviation 0.9 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 5 | 3.5 Points on a scale | Standard Deviation 0.4 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Day 6 | 3.9 Points on a scale | Standard Deviation 0.2 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Extubation period | 3.2 Points on a scale | Standard Deviation 0.7 |
| Remifentanil | Sedation-Agitation From Screening Through the End of Study | Post-extubation period | 3.8 Points on a scale | Standard Deviation 0.8 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Post-extubation period | 4.0 Points on a scale | Standard Deviation 0 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Screening period | 3.7 Points on a scale | Standard Deviation 1.2 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Extubation period | 3.6 Points on a scale | Standard Deviation 0.4 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 4 | 3.1 Points on a scale | Standard Deviation 0.6 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 1 | 2.9 Points on a scale | Standard Deviation 0.8 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 6 | 2.6 Points on a scale | Standard Deviation 0.6 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 2 | 2.9 Points on a scale | Standard Deviation 0.9 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 5 | 3.1 Points on a scale | Standard Deviation 1.1 |
| Propofol | Sedation-Agitation From Screening Through the End of Study | Day 3 | 3.1 Points on a scale | Standard Deviation 0.6 |
Secondary
Total Dose of Fentanil Administered - Bolus
Data for this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: Up to 10 days
Population: ITT Population. Only participants dosed with Fentanil were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Propofol | Total Dose of Fentanil Administered - Bolus | 5.1 ug/kg | Standard Deviation 3.6 |
Secondary
Total Dose of Propofol Administered - Bolus
Data from this measure come from infusion pump display; the infusion pump infuses medication (analgesics and sedative agents) into the participant's circulatory system.
Time frame: Up to 10 days
Population: ITT Population. Only participants dosed with Propofol were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Remifentanil | Total Dose of Propofol Administered - Bolus | 1.5 mg/kg | Standard Deviation 0.4 |
| Propofol | Total Dose of Propofol Administered - Bolus | 5.5 mg/kg | Standard Deviation 4.5 |