Palliative Care
Conditions
Keywords
Sedation, End-of-life, Palliative care, Midazolam, Sodium oxybate
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.
Interventions
DRUGSodium Oxybate injection
* 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.
DRUGMidazolam injection
* 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.
Sponsors
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Masking description
Participants won't be aware of the sedative treatment administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reaching and maintaining a comfort sedation defined by a target RASS score of -4 | From inclusion until death, up to 12 hours | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | From inclusion until death, up to 12 hours | Number of clinical adverse events recorded in both arms. |
| Survival time | From inclusion until death, up to 12 hours | Time span between induction of sedation and death. |
Countries
Monaco
Contacts
STUDY_DIRECTORJean-François CIAIS, MD
Centre Hospitalier Princesse Grace - Monaco
Outcome results
None listed