Estimation of the Effective Dose (ED) 95 of Intrathecal Hyperbaric Prilocaine 2% for Scheduled Cesarean Delivery.

Estimation of the Effective Dose (ED) 95 of Intrathecal Hyperbaric Prilocaine 2% for Scheduled Cesarean Delivery : a Dose-finding Study Based on the Continual Reassessment.

Prilocaine is a local anesthetic drug which as an intermediate duration of action shorter than bupivacaine 0,5% that is usually used for spinal anesthesia in scheduled cesarean section. No study has yet investigated the use of hyperbaric (HB) prilocaine 2% for intrathecal anesthesia in cesarean section. The aim of this study is to determine the Effective Dose (ED) 95 of hyperbaric (HB) prilocaine 2% by using the Continual Reassessment Method (CRM)

Study Overview

• Status: Completed
• Conditions: Pregnant Women
• Intervention / Treatment: Drug: Hyperbaric prilocaine 2%; Drug: Hyperbaric prilocaine 2%; Drug: Morphine

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels Capital Region, Belgium, 1000
    • University Hospital Saint-Pierre, Université Libre de Bruxelles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• American Society of Anesthesiologists physical status (ASA) < III
• Age 18-40 year
• Body Weight <100 kg
• Height between 160 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
• Pre eclampsia and eclampsia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 : HB Prilocaine 2%,(60mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 2 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 3 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 4 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 5 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 6 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 7 : HB Prilocaine 2%,(45-70mg); Dose-finding study with 4 subjects per dose and a maximum of 40 paturients.To identify the dose to give for reaching the ED95 (effective dose for 95% subjects), Hyperbaric prilocaine 2% will be adminitrated at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 8 : HB Prilocaïne 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 9 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine
Experimental: Cohort 10 : HB Prilocaine 2%,(45-70mg); 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% will be administered at the dose initial of 60 mg in the cohort 1 (4 subjects), then the dose will be adjusted in the next cohorts using the Continual Reassessment Method (CRM). The dose range will be from 45 to 70mg.	Drug: Hyperbaric prilocaine 2%; Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Hyperbaric prilocaine 2%; The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine; Other Names: Tachipri; Drug: Morphine; 100µg morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Success of anesthesia	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	during surgery (average 1 hour)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Sensory block assessed as loss of sensation to pinprick, cold and pressure	Every 2 minutes after spinal anesthesia during 15 minutes, then every 5 minutes until the end of surgery, thereafter, once every hour until total regression of sensory block (T12-S1).	Until complete release of sensory block (T12-S1) (average 4 hours)
Side-effects (nausea, vomiting,pruritus)	from 15 minutes after spinal anesthesia and every 4 hours for 24 hours (score 0=no symptoms; 1=symptoms with no treatment necessary; 2=symptoms present and treated)	up to 24 hours after surgery
Transient neurologic symptoms (TNS)	TNS are defined as pain and/or dysesthesia occured after complete release of sensory block at the gluteal level, at the tights and at the legs. At Day 0, Day 1, day 3 and Day 5	up to 5 Days
Pain as assessed by Visual Analogue Scale (VAS)	Pain levels will be determined every 5 minutes during surgery. The Visual Analogue score (scale : 0 = no pain; 10= worst pain imaginable)	during surgery (average 1 hour)
Number of participants with low blood pressure	Arterial blood pressure will be measured at every 2.5 minute during the first 15 minutes, then at every 5 minutes until the end of surgery. A blood pressure lower is define as a blood pressure lower than 20% or more than the basal blood pressure (Systolic blood pressure before spinal anesthesia)	during surgery (average 1 hour)
Methemoglobinemia	Methemoglobin level measured in umbilical cord blood of new born at the delivery	at delivery (average 1 hour)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Saint Pierre
• Investigators: Study Director: Panayota KAPESSIDOU, MD, PhD, University Hospital Saint-Pierre (CHU Saint-Pierre), Université Libre de Bruxelles (ULB); Principal Investigator: Philippe Goffard, MD, University Hospital Saint-Pierre (CHU Saint-Pierre), Université Libre de Bruxelles (ULB)

Publications and helpful links

General Publications

• Camponovo C, Fanelli A, Ghisi D, Cristina D, Fanelli G. A prospective, double-blinded, randomized, clinical trial comparing the efficacy of 40 mg and 60 mg hyperbaric 2% prilocaine versus 60 mg plain 2% prilocaine for intrathecal anesthesia in ambulatory surgery. Anesth Analg. 2010 Aug;111(2):568-72. doi: 10.1213/ANE.0b013e3181e30bb8. Epub 2010 Jun 7.
• Gupta PK, Chevret S, Zohar S, Hopkins PM. What is the ED95 of prilocaine for femoral nerve block using ultrasound? Br J Anaesth. 2013 May;110(5):831-6. doi: 10.1093/bja/aes503. Epub 2013 Feb 7.

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: July 24, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Scheduled cesarean delivery,spinal anesthesia,local anesthesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Prilocaine; Morphine
• Other Study ID Numbers: B076201524085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No