Sodium Oxybate Versus Midazolam for Comfort Sedation

Palliative Care Clinical Trial

— ONAMI  

Official title:

Sodium Oxybate Versus Midazolam for Comfort Sedation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05085873
• Other study ID #: 2020-CHITS-002
• Secondary ID: 2021-001961-19
• Status: Completed
• Phase: Phase 4
• Start date: October 14, 2021
• Est. completion date: October 10, 2023

Study information

• Verified date: March 2024
• Source: Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 10, 2023
• Est. primary completion date: October 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Palliative Care

Intervention

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.
• 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.

Locations

Country	Name	City	State
Monaco	Centre Hospitalier Princesse Grace	Monaco

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer

Country where clinical trial is conducted

Monaco, 

References & Publications (1)

Ciais JF, Jacquin PH, Pradier C, Castelli-Prieto M, Baudin S, Tremellat F. Using Sodium Oxybate (Gamma Hydroxybutyric Acid) for Deep Sedation at the End of Life. J Palliat Med. 2015 Oct;18(10):822. doi: 10.1089/jpm.2015.0221. Epub 2015 Aug 24. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Adverse events	Number of clinical adverse events recorded in both arms.	From inclusion until death, up to 12 hours
Secondary	Survival time	Time span between induction of sedation and death.	From inclusion until death, up to 12 hours