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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Open Label, Multicentre Study to Compare the Pharmaco-economic Implications of an Analgesia Based Regimen With Remifentanil and a Conventional Sedation Based Regimen Using Propofol in Medical and Post-surgical ICU Subjects Requiring Mechanical Ventilation for at Least 2 Days.

Conditions
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Analgesia

Intervention / Treatment
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* Drug: Remifentanil
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil<br>remifentanil | Drug: Remifentanil<br>* analgesia in medical and post-surgical Intensive Care Unit subjects requiring mechanical ventilation<br>|
| Active Comparator: Propofol<br>Propofol infusion | Drug: Propofol<br>* conventional sedation in medical and post-surgical Intensive Care Unit subjects requiring mechanical<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Up to 38 days (912 hours) | 
| Duration of Time on Mechanical Ventilation (Modified-Intent-to-Treat Population) | Time from start of mechanical ventilation until actual extubation. | Up to 38 days (912 hours) | 
| Duration of Time on Mechanical Ventilation (Per-Protocol Population) | Time from start of mechanical ventilation until actual extubation | Up to 38 days (912 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to 38 days (912 hours) | 
| Duration of Extubation | Duration of extubation was measured. | up to 38 days (912 hours) | 
| Duration of Weaning | Duration of weaning (the time from the intubation until the recovery of natural respiratory ability) was measured. | up to 38 days (912 hours) | 
| 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. | Up to 10 days (240 hours) | 
| 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. | up to 10 days (240 hours) | 
| 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. | up to 10 days (240 hours) | 
| 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. | Up to 10 days | 
| 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. | up to 10 days | 
| 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. | Up to 10 days | 
| 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. | up to 10 days | 
| 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. | Up to 10 days | 
| 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. | Up to 10 days | 
| 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. | Up to 38 Days | 
| 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. | Up to 38 days | 
| 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. | Day 7 | 
| 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. | Days 8, 9, and 10 | 
| 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. | Up to 38 days | 
| 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. | Screening through End of Study, up to 38 days | 
| 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. | Day 5 | 
| 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. | up to 38 days | 
| 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. | Up to 38 days | 
| 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. | Days 8, 9, and 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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analgesia, Mechanical ventilation, pharmaco-economic, ICU