ONAMI: Sodium Oxybate Versus Midazolam for Comfort Sedation

Sponsor

Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer (Other)

Overall Status

Recruiting

CT.gov ID

NCT05085873

Collaborator

(none)

Enrollment

Location

Arms

23.6

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Palliative Care	Drug: Sodium Oxybate injection Drug: Midazolam injection	Phase 4

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Masking Description:

Participants won't be aware of the sedative treatment administered.

Primary Purpose:

Supportive Care

Official Title:

Sodium Oxybate Versus Midazolam for Comfort Sedation

Actual Study Start Date :

Oct 14, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sodium oxybate	Drug: Sodium 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. Other Names: Gamma-Hydroxybutyric acid 4-hydroxybutanoic acid
Active Comparator: Midazolam	Drug: Midazolam 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.

Arm

Intervention/Treatment

Experimental: Sodium oxybate

Drug: Sodium 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.

Other Names:

Gamma-Hydroxybutyric acid

4-hydroxybutanoic acid

Active Comparator: Midazolam

Drug: Midazolam 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.

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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