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

Study Overview
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Brief Summary
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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)

Official Title
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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.

Conditions
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Pregnant Women

Intervention / Treatment
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* Drug: Hyperbaric prilocaine 2%
* Drug: Hyperbaric prilocaine 2%
* Drug: Morphine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 : HB Prilocaine 2%,(60mg)<br>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%<br>* The dose of 60 mg of Hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 2 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 3 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 4 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 5 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 6 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 7 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 8 : HB Prilocaïne 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 9 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|
| Experimental: Cohort 10 : HB Prilocaine 2%,(45-70mg)<br>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%<br>* Varying dose according to sensitive response of previous subjects. All study doses of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine<br>* Other names: Tachipri;Drug: Morphine<br>* 100µg morphine<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Scheduled cesarean delivery,spinal anesthesia,local anesthesia