Comparison of Chloroprocaine vs Lidocaine for Epidural Anesthesia in Cesarean Delivery

• Sponsor: University of Arkansas (Other)
• Overall Status: Completed
• CT.gov ID: NCT03414359
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.3
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

Regional anesthesia is commonly used for elective and emergency cesarean delivery. It provides numerous safety advantages when compared to general anesthesia for both the mother and fetus1. Epidurals also have the added benefit of being able to provide pain relief throughout labor and in the event of cesarean delivery, epidural analgesia can be "extended" to provide surgical anesthesia. Numerous studies have been performed to assess the onset times of various local anesthetics when administered through an epidural catheter. Attempts to reduce anesthetic onset time and improve the quality of intraoperative analgesia have been attempted by using different local anesthetic solutions and by the addition of other drugs to the epidural solution (such as epinephrine, fentanyl and sodium bicarbonate).

Condition or Disease	Intervention/Treatment	Phase
Surgical Anesthesia, Cesarean Section	Drug: 2% Lidocaine; Drug: 3% Chloroprocaine	Early Phase 1

Detailed Description

Regional anesthesia is commonly used for elective and emergency cesarean delivery. It provides numerous safety advantages when compared to general anesthesia for both the mother and fetus1. Epidurals also have the added benefit of being able to provide pain relief throughout labor and in the event of cesarean delivery, epidural analgesia can be "extended" to provide surgical anesthesia. Numerous studies have been performed to assess the onset times of various local anesthetics when administered through an epidural catheter. Attempts to reduce anesthetic onset time and improve the quality of intraoperative analgesia have been attempted by using different local anesthetic solutions and by the addition of other drugs to the epidural solution (such as epinephrine, fentanyl and sodium bicarbonate).

A recent meta-analysis concluded that the optimum local anesthetic solution for extending a labor epidural from analgesia to surgical anesthesia has yet to be determined 2. In 1994, a retrospective study compared 1.5% lidocaine/bicarbonate/epinephrine mixture to 3% chloroprocaine in parturients with pre-existing epidural catheters for urgent cesarean delivery3. It was found that the chloroprocaine group had a significantly faster onset of anesthesia compared to the lidocaine group. Both drugs provided excellent anesthesia. However a high quality study comparing 3% chloroprocaine with 2% lidocaine/ epinephrine/ bicarbonate/ fentanyl (LEBF) in terms of anesthetic onset times has yet to be performed.

Women in labor frequently request an epidural to provide pain relief. Epidural pain relief is commonly provided by the administration of a low concentration of local anesthetic and opioid solution through an epidural catheter. This solution is delivered by an automated epidural infusion pump. In the event that a cesarean delivery is required, the pre-existing epidural is frequently used to administer a higher concentration anesthetic solution to allow pain free cesarean delivery. This is commonly referred to as an "epidural top up" or as an "extension of the epidural block." Standard practice at University of Arkansas for Medical Sciences (UAMS) for an epidural top up is Lidocaine, Epinephrine, Bicarbonate and Fentanyl (LEBF) or 3% chloroprocaine. These two mixtures are routinely and almost exclusively used for epidural cesarean delivery. The decision on which mixture to use is based solely on physician preference. It is likely that the LBEF mixture is used more frequently but the investigators consider both local anesthetic mixtures as equals and the standard of care at UAMS. The investigators do not use any other local anesthetics (unless there are very specific reasons).

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind Study Comparing 3% Chloroprocaine Versus 2 % Lidocaine/ Epinephrine/ Bicarbonate/ Fentanyl for Epidural Anesthesia in Elective Cesarean Delivery
• Actual Study Start Date: Feb 15, 2018
• Actual Primary Completion Date: Mar 27, 2019
• Actual Study Completion Date: Mar 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2% Lidocaine Group LEBF received 20 ml of 2% lidocaine (combined with the following adjuncts [0.15 ml of 0.1% epinephrine, 2 ml of 8.4% sodium bicarbonate and 2 ml of 100 mcg fentanyl	Drug: 2% Lidocaine; 2% Lidocaine using a combined spinal-epidural (CSE); Other Names: Xylocaine
Experimental: 3% Chloroprocaine 20 ml of 3% chloroprocaine with 4 ml 0.9% sodium chloride	Drug: 3% Chloroprocaine; 3% Chloroprocaine using a combined spinal-epidural (CSE); Other Names: Nesacaine

Outcome Measures

Primary Outcome Measures

1. The Onset Time to Surgical Anesthesia [Up to 35 minutes]

   The onset time to surgical anesthesia, as reported by the participant using a standard procedure This will be measured by the time taken from the end of the epidural loading dose to develop a loss of touch sensation using a neurotip® (Owen Mumford, USA) device bilaterally at the T7 dermatomal level using a non-inferiority study design. A non-inferiority limit of 3 minutes was chosen apriori.

Secondary Outcome Measures

1. Secondary Outcome: Number of Participants With Requirement for Intraoperative Analgesia Supplementation [1 hour]

   This requirement for any rescue medications to control discomfort or pain during CD

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• ≥ 18 years of age for the mother

• Singleton pregnancy

• Gestation > 36 weeks

• American Society of Anesthesiologist (ASA) class II

• Provides written consent

• Infant of mother

Exclusion Criteria:

• Patient refusal

• Non-elective or urgent/emergent cesarean sections

• ASA class III or above

• Unable to understand English

• Significant back surgery or scoliosis

• Known fetal abnormality

• Weight > 120 kg

• Height < 150 cm

• Allergy to local anesthetics

• Concurrent use of sulfonamides

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas

Investigators

• Principal Investigator: Nadir Sharawi, MD, University of Arkansas

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 13, 2018

More Information

Publications

None provided.

• Responsible Party: University of Arkansas
• ClinicalTrials.gov Identifier: NCT03414359
• Other Study ID Numbers: 207313
• First Posted: Jan 29, 2018
• Last Update Posted: Apr 13, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Lidocaine; Chloroprocaine

Study Results

Participant Flow

Arm/Group Title	2% Lidocaine	3% Chloroprocaine
Arm/Group Description	2% Lidocaine: 2% Lidocaine (with epinephrine, bicarbonate, and fentanyl) using a combined spinal-epidural (CSE)	3% Chloroprocaine: 3% Chloroprocaine using a combined spinal-epidural (CSE)
Period Title: Overall Study
STARTED	35	35
COMPLETED	34	33
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	2% Lidocaine	3% Chloroprocaine	Total
Arm/Group Description	2% Lidocaine: 2% Lidocaine (with epinephrine, bicarbonate, and fentanyl) using a combined spinal-epidural (CSE)	3% Chloroprocaine: 3% Chloroprocaine using a combined spinal-epidural (CSE)	Total of all reporting groups
Overall Participants	34	33	67
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	34 100%	33 100%	67 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	27	30	28
Sex: Female, Male (Count of Participants)
Female	34 100%	33 100%	67 100%
Male	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (participants) [Number]
African American	13 38.2%	12 36.4%	25 37.3%
Other	21 61.8%	21 63.6%	42 62.7%
Region of Enrollment (participants) [Number]
United States	34 100%	33 100%	67 100%
BMI (kg/m^2) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kg/m^2]	31	32	31
Gestational age (days) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [days]	273	273	273
Duration of epidural infusion (minutes) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [minutes]	48	49	49

Outcome Measures

1. Primary Outcome

Title	The Onset Time to Surgical Anesthesia
Description	The onset time to surgical anesthesia, as reported by the participant using a standard procedure This will be measured by the time taken from the end of the epidural loading dose to develop a loss of touch sensation using a neurotip® (Owen Mumford, USA) device bilaterally at the T7 dermatomal level using a non-inferiority study design. A non-inferiority limit of 3 minutes was chosen apriori.
Time Frame	Up to 35 minutes

Outcome Measure Data

Analysis Population Description

Per protocol analysis

Arm/Group Title	2% Lidocaine	3% Chloroprocaine
Arm/Group Description	2% Lidocaine: 2% Lidocaine (with epinephrine, bicarbonate, and fentanyl) using a combined spinal-epidural (CSE)	3% Chloroprocaine: 3% Chloroprocaine using a combined spinal-epidural (CSE)
Measure Participants	34	33
Mean (Standard Deviation) [seconds]	558 (269)	655 (258)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2% Lidocaine, 3% Chloroprocaine
	Comments	To exclude a clinically important difference between the LEBF group and the chloroprocaine group, given a standard deviation of 4 minutes, and a non-inferiority margin of 3 minutes difference between groups, 62 mother-infant dyads (31 mother-infant dyads in each arm) are required to have a significance level of 5% and a power of 90%. In total, 70 female patients were recruited to account for any withdrawals.
	Type of Statistical Test	Non-Inferiority
	Comments	As there is no existing data in the literature that clearly defines a clinically significant reduction in the onset time of anesthesia, the non-inferiority margin was defined a priori based on clinical reasoning.
Statistical Test of Hypothesis	p-Value	0.10
	Comments	The a priori threshold for statistical significance is, <0.05
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Secondary Outcome: Number of Participants With Requirement for Intraoperative Analgesia Supplementation
Description	This requirement for any rescue medications to control discomfort or pain during CD
Time Frame	1 hour

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2% Lidocaine	3% Chloroprocaine
Arm/Group Description	2% Lidocaine: 2% Lidocaine (with epinephrine, bicarbonate, and fentanyl) using a combined spinal-epidural (CSE)	3% Chloroprocaine: 3% Chloroprocaine using a combined spinal-epidural (CSE)
Measure Participants	34	33
Count of Participants [Participants]	4 11.8%	7 21.2%

Adverse Events

Time Frame	During inpatient admission, approximately three days
Adverse Event Reporting Description	local anesthetic systemic toxicity (LAST), post-dural puncture headache (PDPH) and high spinal (defined as upper limb weakness)
Arm/Group Title	2% Lidocaine		3% Chloroprocaine
Arm/Group Description	2% Lidocaine: 2% Lidocaine (with epinephrine, bicarbonate, and fentanyl) using a combined spinal-epidural (CSE)		3% Chloroprocaine: 3% Chloroprocaine using a combined spinal-epidural (CSE)
All Cause Mortality
	2% Lidocaine		3% Chloroprocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)
Serious Adverse Events
	2% Lidocaine		3% Chloroprocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	2% Lidocaine		3% Chloroprocaine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		1/33 (3%)
Nervous system disorders
Post dural puncture headache	0/34 (0%)	0	1/33 (3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.