Estimation of the ED95 of Intrathecal Hyperbaric Prilocaine 2% With Sufentanyl for Scheduled Cesarean Delivery : a Dose-finding Study Bases on the Continual Reassessment Method (CRM)
Overview
- Phase
- Phase 2
- Intervention
- HB Prilocaine 2%
- Conditions
- Pregnant Women
- Sponsor
- Centre Hospitalier Universitaire Saint Pierre
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- Success of Anesthesia
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
Hyperbaric bupivacaine 0.5% associated with opioids is the local anesthetic the most commonly used for spinal injection in cesarean section. Nevertheless, its use often results in a long duration of motor nerve block and a haemodynamical instability. Recently developped, the Prilocaine, with its new 2% hyperbaric formulation, seems to offer a good alternative for hyperbaric bupivicaine. A first study has determined the ED95 of hyperbaric prilocaine 2% for intrathecal anesthesia in scheduled cesarean delivery. As opioid adjuvants potentiate the effect of the local anesthetics while decreasing their dose-related side effects, the aim of this study is to determine the ED95 of hyperbaric prilocaine 2% with sufentanyl for scheduled cesarean delivery under spinal anesthesia,by using the Continual Reassessment Method (CRM)
Investigators
Eligibility Criteria
Inclusion Criteria
- •American Society of Anesthesiologists physical status (ASA) \< III
- •Age 18-40 year
- •Body Weight \<100 kg
- •Height between 155 and 175 cm
- •Gestational age\>37 SA
- •Elective cesarean delivery
- •Singleton pregnancy
- •Non complicated pregnancy
- •Signed informed consent obtained prior to any study specific assessments and procedures
Exclusion Criteria
- •Twin pregnancy
- •History of 2 cesarean section or more
- •Diabetes and gestational diabetes
- •Placenta praevia
- •Congenital foetal abnormality
- •Patient in labour
- •Membrane rupture
- •Known allergy to local anaesthetics
- •Disagreement of the patient
- •Pregnancy-induced hypertension
Arms & Interventions
Cohort 1 : HB prilocaine 2%, 45mg
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2%
Cohort 1 : HB prilocaine 2%, 45mg
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 1 : HB prilocaine 2%, 45mg
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 2 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 2 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 2 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 3 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 3 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 3 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 4 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 4 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 4 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 5 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 5 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 5 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 6 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 6 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 6 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 7 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 7 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 7 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 8 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 8 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 8 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 9 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 9 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 9 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Cohort 10 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: HB Prilocaine 2% (varying dose)
Cohort 10 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Sufentanil
Cohort 10 : HB prilocaine 2%, (30-55mg)
Dose-finding study with 4 subjects per dose and a maximum of 40 parturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2%, associated with sufentanyl, will be administrated at the dose initial of 45 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). Possible dose levels are 30, 35, 40, 45, 50, 55mg.
Intervention: Morphine
Outcomes
Primary Outcomes
Success of Anesthesia
Time Frame: during surgery (average 1 hour)
The nerve blockade will be considered as success when a bilateral T4 level will reach in 15 minutes after intrathecal injection without additional epidural injection needed within 45 minutes peri-operative ; no pain at the skin incision, no pain during 45 minutes after the skin incision
Secondary Outcomes
- Number of Participants Needing Vasopressors(during surgery (average 1 hour))
- Number of Participants With Transient Neurologic Symptoms (TNS)(up to 5 Days)
- Sensitive Block Duration(Until complete release of sensory block (T12-S1) (average 4 hours))
- Sensitive Block at End of Surgery(Until complete release of sensory block (T12-S1) (average 4 hours))
- Motor Block Duration(Until complete release of motor block (Bromage scale = 1; average 4 hours))
- Bromage Motor Block Level at End of Surgery(Until complete release of motor block (average 4 hours))
- Newborn Apgar Score(up to 10 minutes after baby extraction)
- Newborn Methemoglobinemia (MetHb)(average 1 hour)
- Number of Participants With Nausea or Vomiting(up to 24 hours after surgery)
- Number of Participants With Pruritus(Up to 24 hours after surgery)
- Number of Participants With Urinary Retention(Up to 24 hours after surgery)
- Number of Participants With Dizziness(Up to 24 hours after surgery)
- Number of Satisfied Participants(up to 1 hour after surgery)