Estimation of the ED95 of Intrathecal Hyperbaric Prilocaine 2% With Sufentanyl for Scheduled Cesarean Delivery

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)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03036384

Enrollment

Registered

2017-01-30

Start date

2016-03-31

Completion date

2016-11-30

Last updated

2020-05-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pregnant Women

Keywords

scheduled cesarean delivery, spinal anesthesia, local anesthesia

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)

Interventions

DRUGHB Prilocaine 2% (varying dose)

Varying dose of hyperbaric (HB) prilocaine 2% according to sensitive response of previous subjects. The dose of hyperbaric prilocaine 2% will be administrated intrathecally with 100µg of morphine and 2.5µg of sufentanyl

DRUGHB Prilocaine 2%

The dose of 45mg of hyperbaric (HB) prilocaine 2% will be administrated intrathecally with 100µg of morphine and 2.5µg of sufentanyl

DRUGSufentanil

2.5µg sufentanyl

DRUGMorphine

100 µg Morphine

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 40 Years

Healthy volunteers

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 * Pre eclampsia and eclampsia

Design outcomes

Primary

Measure	Time frame	Description
Success of Anesthesia	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

Measure	Time frame	Description
Sensitive Block Duration	Until complete release of sensory block (T12-S1) (average 4 hours)	Level of Sensory block assessed as loss of sensation to cold, every 2 minutes after spinal anesthesia during 15 minutes, then every 5 minutes until the end of surgery, thereafter, once 30 minutes until total regression of sensory block (T12-S1).
Sensitive Block at End of Surgery	Until complete release of sensory block (T12-S1) (average 4 hours)	Level of Sensory block assessed as loss of sensation to cold, every 2 minutes after spinal anesthesia during 15 minutes, then every 5 minutes until the end of surgery, thereafter, once 30 minutes until total regression of sensory block (T12-S1). For this study, dermatome levels are depicted on a scale ranging from 1 to 18. (1 to 12 = T1-T12 thoracic levels; 13 to 17 = L1-L5 lumbar levels; 18 = S1 sacral level)
Motor Block Duration	Until complete release of motor block (Bromage scale = 1; average 4 hours)	Bromage scale (1 = no motor block; 2 = hip blocked; 3 = hip and knee blocked; and 4 = hip, knee, and ankle blocked) was used to evaluate the motor block every 15 minutes after spinal anaesthesia (T0) and until the end of surgery. Duration was defined from the time of the spinal injection until Bromage scale = 1.
Bromage Motor Block Level at End of Surgery	Until complete release of motor block (average 4 hours)	Bromage scale (1 = no motor block; 2 = hip blocked; 3 = hip and knee blocked; and 4 = hip, knee, and ankle blocked) was used to evaluate the motor block every 15 min after spinal anaesthesia (T0) and until the end of surgery.
Newborn Apgar Score	up to 10 minutes after baby extraction	Newborn Apgar score assessed at 1, 5, 10 minutes after baby extraction. The Apgar score is determined by evaluating the newborn baby on five simple criteria on a scale from 0 to 2, then summing up the five values thus obtained. The overall resulting score ranges from 0 to 10 ( 0-3 : severely depressed, 4-6 : Moderately depressed and 7-10 : Excellent condition). The five criteria are summarized using words chosen to form an abbreviation (Appearance, Pulse, Grimace, Activity, Respiration).
Newborn Methemoglobinemia (MetHb)	average 1 hour	Newborn Methemoglobinemia (MetHb) will be assessed at delivery by cordal blood sample, as a routine control, and expressed as a percentage of total hemoglobinemia.
Number of Participants With Nausea or Vomiting	up to 24 hours after surgery	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)
Number of Participants With Transient Neurologic Symptoms (TNS)	up to 5 Days	TNS are defined as pain and/or dysesthesia occurred after complete release of sensory block at the gluteal level, at the thighs and at the legs. At Day 0, Day 1, Day 3 and Day 5
Number of Participants With Pruritus	Up to 24 hours after surgery	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)
Number of Participants With Urinary Retention	Up to 24 hours after surgery	All parturients will be questioned for urinary retention (yes or no)
Number of Participants With Dizziness	Up to 24 hours after surgery	All parturients will be questioned for dizziness (yes or no)
Number of Satisfied Participants	up to 1 hour after surgery	Maternal satisfaction (yes or no) will be assessed 1 hour after surgery in the PACU (Post Anesthesia Care Unit)
Number of Participants Needing Vasopressors	during surgery (average 1 hour)	Arterial blood pressure will be measured at every 2.5 minute during surgery, then at every 20 minutes in the PACU (Post Anesthesia Care Unit). Vasopressors were given for patients with low blood pressure. A low blood pressure is defined as a blood pressure lower than 20% or more than the basal blood pressure (Systolic blood pressure before spinal anesthesia).

Countries

Belgium

Participant flow

Recruitment details

All participants were recruited at CHU Saint-Pierre.

Pre-assignment details

Possible doses of HB prilocaine range from 30 to 55mg, but actual administrated doses will be defined by CRM

Participants by arm

Arm	Count
35mg HB Prilocaine	4
40mg HB Prilocaine	12
45mg HB Prilocaine	20
50mg HB Prilocaine	4
Total	40

Baseline characteristics

Characteristic	35mg HB Prilocaine	40mg HB Prilocaine	45mg HB Prilocaine	50mg HB Prilocaine	Total
Age, Continuous	29 years STANDARD_DEVIATION 8.76	35.08 years STANDARD_DEVIATION 5.11	32.85 years STANDARD_DEVIATION 4.93	29.85 years STANDARD_DEVIATION 5.94	32.75 years STANDARD_DEVIATION 5.69
Gravity	3 number of pregnancies STANDARD_DEVIATION 1.41	2.17 number of pregnancies STANDARD_DEVIATION 1.03	3.1 number of pregnancies STANDARD_DEVIATION 1.98	2 number of pregnancies STANDARD_DEVIATION 0.96	2.70 number of pregnancies STANDARD_DEVIATION 1.47
Length	159.5 cm STANDARD_DEVIATION 4.93	164.42 cm STANDARD_DEVIATION 4.45	162.8 cm STANDARD_DEVIATION 6.26	157 cm STANDARD_DEVIATION 6.16	162.38 cm STANDARD_DEVIATION 5.89
Parity	1.25 number of deliveries STANDARD_DEVIATION 0.5	0.67 number of deliveries STANDARD_DEVIATION 0.49	1.3 number of deliveries STANDARD_DEVIATION 1.98	0.75 number of deliveries STANDARD_DEVIATION 0.96	1.05 number of deliveries STANDARD_DEVIATION 1.47
Previous Caesarean Section (CS) 1 previous caeserean	2 Participants	5 Participants	10 Participants	1 Participants	18 Participants
Previous Caesarean Section (CS) no previous caeserean	2 Participants	7 Participants	10 Participants	3 Participants	22 Participants
Sex/Gender, Customized Female	4 Participants	12 Participants	20 Participants	4 Participants	40 Participants
Sex/Gender, Customized Male	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Term	38.5 weeks STANDARD_DEVIATION 0.58	38.42 weeks STANDARD_DEVIATION 1.08	38.40 weeks STANDARD_DEVIATION 0.94	38.75 weeks STANDARD_DEVIATION 1.26	38.45 weeks STANDARD_DEVIATION 0.96
Weight	73 kg STANDARD_DEVIATION 16.02	82.17 kg STANDARD_DEVIATION 11.93	79.78 kg STANDARD_DEVIATION 11.6	84.68 kg STANDARD_DEVIATION 2.88	80.31 kg STANDARD_DEVIATION 11.62

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 12	0 / 20	0 / 4
other Total, other adverse events	0 / 4	0 / 12	0 / 20	0 / 4
serious Total, serious adverse events	0 / 4	0 / 12	0 / 20	0 / 4

Outcome results

Primary

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

Time frame: during surgery (average 1 hour)

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Cohort 1	Success of Anesthesia	Success	4 Participants
Cohort 1	Success of Anesthesia	Failure	0 Participants
Cohort 2	Success of Anesthesia	Failure	0 Participants
Cohort 2	Success of Anesthesia	Success	4 Participants
Cohort 3	Success of Anesthesia	Success	4 Participants
Cohort 3	Success of Anesthesia	Failure	0 Participants
Cohort 4	Success of Anesthesia	Failure	3 Participants
Cohort 4	Success of Anesthesia	Success	1 Participants
Cohort 5	Success of Anesthesia	Success	4 Participants
Cohort 5	Success of Anesthesia	Failure	0 Participants
Cohort 6	Success of Anesthesia	Success	4 Participants
Cohort 6	Success of Anesthesia	Failure	0 Participants
Cohort 7	Success of Anesthesia	Success	4 Participants
Cohort 7	Success of Anesthesia	Failure	0 Participants
Cohort 8	Success of Anesthesia	Success	4 Participants
Cohort 8	Success of Anesthesia	Failure	0 Participants
Cohort 9	Success of Anesthesia	Success	3 Participants
Cohort 9	Success of Anesthesia	Failure	1 Participants
Cohort 10	Success of Anesthesia	Failure	1 Participants
Cohort 10	Success of Anesthesia	Success	3 Participants

Secondary

Bromage Motor Block Level at End of Surgery

Bromage scale (1 = no motor block; 2 = hip blocked; 3 = hip and knee blocked; and 4 = hip, knee, and ankle blocked) was used to evaluate the motor block every 15 min after spinal anaesthesia (T0) and until the end of surgery.

Time frame: Until complete release of motor block (average 4 hours)