Sodium Oxybate Versus Midazolam for Comfort Sedation

Study Overview
=================
Brief Summary
-----------------
The study aims at deepen the proof level of sodium oxybate use for comfort sedation at the end of life in a palliative care unit by comparing it to midazolam in a prospective randomized study with blinded efficacy evaluation. The study will be carried out for a period of 24 months with a recruitment objective of 22 patients with refractory suffering and with a short-term prognosis.

Detailed Description
-----------------
In certain cases, terminally-ill patients may show persistent symptoms despite numerous efforts to find a comfort treatment without causing impaired consciousness. In these cases and after a collegial discussion, sedation may be offered. Midazolam is then the most typically used sedative agent. However, it has limitations: frequent awakenings, tolerance and major respiratory depression. Furthermore, the use of midazolam as a gold standard in palliative sedation at the end of life falls under expert consensus without a high level of evidence. Sodium oxybate (GammaOH®), is an ancient molecule used in anesthesia and other medical fields. It appears to be an attractive alternative to midazolam. Study hypothesis is as follows: deep sedation induced by sodium oxybate (RASS: -4 or -5) is more constant and sustainable than by using midazolam which can cause fluctuating effects and requires frequent dosage adjustments. The single-blind clinical trial aims at comparing the possibility to obtain constant deep sedation using midazolam or sodium oxybate. Before the induction, the patient is not aware of the medication used. The medical team must be aware of it because the two administration procedures are too different.

Official Title
-----------------
Sodium Oxybate Versus Midazolam for Comfort Sedation

Conditions
-----------------
Palliative Care

Intervention / Treatment
-----------------
* Drug: Sodium Oxybate injection
* Drug: Midazolam injection


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: patient hospitalized in a palliative care unit patient aged 18 or over patient with an estimated vital prognosis of a few hours to a few days* patient with persistent suffering despite optimal palliative care* patient gave informed consent in advance or if unable to do so, consent given by a family member or legal representative (patients under guardianship) patient covered by a social security scheme. * Validated after collegial and multidisciplinary discussion including the opinion of a doctor outside the palliative care team. Exclusion Criteria: contraindication or known allergy to sodium oxybate or midazolam significant risk of seizure venous access not possible pregnancy or breastfeeding person in exclusion period from another research protocol at the time of consent signing any condition which in the investigator's opinion could increase and jeopardize persons safety in case of research participation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sodium oxybate<br> | Drug: Sodium Oxybate injection<br>* Induction dosage : 60 mg/kg by direct intravenous injection. Continuous dosage : 45 mg/kg/h by continuous intravenous injection. Additional dosage if the Richmond Agitation Sedation Scale (RASS) score exceeds -4 : 1000 mg sodium oxybate by direct intravenous injection bolus every hour at most until RASS score reaches -4. Sedation maintained until patient death.<br>* Other names: 4-hydroxybutanoic acid;|
| Active Comparator: Midazolam<br> | Drug: Midazolam injection<br>* Induction dosage : 1 mg every 3 min by direct intravenous injection until RASS score reaches -4 (with a maximum of 30 min). Continuous dosage : Half of titration dosage every hour by continuous intravenous injection. Additional dosage if the RASS score exceeds -4 : 1 mg every 3 min by direct intravenous injection (without exceeding 10 mg/h). Sedation maintained until patient death.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reaching and maintaining a comfort sedation defined by a target RASS score of -4 | Treatment is defined as successful when reaching and consistently maintaining the target score; treatment is defined as not successful when not reaching the target score at induction or not maintaining a score of <= -4 for patients who initially reached the target. | From inclusion until death, up to 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of clinical adverse events recorded in both arms. | From inclusion until death, up to 12 hours | 
| Survival time | Time span between induction of sedation and death. | From inclusion until death, up to 12 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Sedation, End-of-life, Palliative care, Midazolam, Sodium oxybate