Randomized Controlled Trial of Combined Lidocaine - Chlorprocaine in Labor Epidural Analgesia.

NCT06302257 | Not Yet Recruiting Phase 4

• 1 other identifier: 0532-23-HMO
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Abstract: Background: The current "gold standard" epidural analgesia involves some undesirable side effects such as motor and sympathetic blockade. Here, the investigators suggest a new approach for inducing prolonged differential pain blockade during labor by selectively targeting local anesthetic chloroprocaine to the pain-related peripheral (nociceptive) fibers. The investigators approach involves nociceptor-selective anesthesia by selective targeting of ionized local anesthetics into nociceptive fibers via activation of nociceptor-specific TRPV1 channels. The authors demonstrated that activation of these channels by specific TRPV1-agonists (capsaicin or the local anesthetic lidocaine), allows entry of a polarized, membrane-impermeable lidocaine derivative (QX-314) specifically into nociceptive neurons, inhibiting their activity and pain blockade, without causing other neural effects. Capsaicin and QX-314 are not suitable for clinical use, as capsaicin causes severe injection pain and QX-314 is neurotoxic. Here, the investigators use lidocaine as the TRPV1 agonist, and use the high pKa chloroprocaine as the ionized local anesthetic instead of the toxic QX-314. Both drugs are in routine clinical use, but have not been described in co-administration before. The investigators preclinical results show that co-administration of chloroprocaine with TRPV1 agonists, leads to prolonged nociceptor-specific analgesia. KKK Hypothesis: The investigators hypothesize that co-administration of epidural lidocaine (to activate TRPV1 channels) and chloroprocaine (as a polarized local anesthetic which can gain preferential access to nociceptors via opened TRPV1 pores) will elicit selective nociceptive-anesthesia. Methodology: This study assess epidural local analgesia in nulliparous labor. There are 2 stages: Stage 1: Prior to direct comparison of lidocaine (Group L), chloroprocaine (Group C), and a lidocaine-chloroprocaine combination (Group L-C), the investigators first determine equipotential doses of epidural chloroprocaine and lidocaine using double-blinded up-down sequential analysis using the well-established minimum local anesthetic concentration (MLAC or ED50) design. ED50 is estimated using Dixon-Massey analysis and Wilcoxon and Litchfield probit regression. Stage 2: The main phase of the study involves a randomized double-blinded comparison between Groups L, C and L-C where all drug concentrations are based on the ED50/MLAC from the Stage 1. The primary endpoint is a composite measure of selective nociceptive analgesia (VAS pain score / modified Bromage motor score). Secondary outcomes are: 1. pain (VAS 0-100), 2. modified Bromage motor score, 3. thermal imaging of feet and hands, 4. sensory assessment to cold sensation using ice, 5. anesthesia requirement from the PCEA pump, 6. maternal blood pressure. 7. ambulation, and pushing ability in labor. Primary endpoint is assessed using repeated measures ANOVA (first 30-min) and mixed models ANOVA until first analgesic request. Implications: Positive findings will be the first evidence in humans of nociceptor-specific local anesthesia; will provide a more effective neuraxial analgesia protocol for labor, and will lead to future studies of systemic nociceptor-specific local anesthesia.

Conditions

Labor Pain

Keywords

Pain; Labor; Analgesia; Local anesthetic; Epidural; Randomized controlled trial; Lidocaine; Chloroprocaine; Visual analogue scale

Outcome Measures

Primary Outcomes (1)

• VAS pain score / modified Bromage motor block score

  Pain (VAS 0-100) where the anchors of the VAS score are 0=no pain, 100=worst pain , assesed 30 minutes after placing epidural catheter, , up until the first epidural top-up imaginable. Modified Bromage motor block score where the scores are determined as follows: 1 = unable to move legs or feet; 2 = unable to flex knees, free movement of feet; 3 = just able to flex knees with free movement of feet; 4 = free movement of legs and feet; 5 = able to perform partial knee-bend movements while standing

  24 Hours

Secondary Outcomes (5)

• Segmental sympathectomy

  24 hours

• Sensory assessment to cold sensation

  24 hours

• Anesthesia requirement.

  24 hours

• Pushing ability in labor.

  24 hours

• Maternal Blood pressure

  24 hours

Study Arms (3)

lidocaine alone

ACTIVE COMPARATOR

Bolus: 20mL MLAC% of lidocaine, administered as incremental test dose over 5 minutes; as in all routine epidurals by our hospital protocol, the incremental test dose is preferred to using classical surgical test doses (which expose the patient to excessive local anesthetic concentrations).

Drug: Lidocaine

Chlorprocaine only

EXPERIMENTAL

Bolus: 20mL MLAC% of chlorprocaine, administered as incremental test dose over 5 minutes; as above, no other test doses are used.

Drug: Chlorprocaine

Lidocaine-chlorprocaine combination

EXPERIMENTAL

Bolus: 10mL MLAC% of lidocaine plus 10mL MLAC% of chlorprocaine, mixed in a 20mL syringe, administered as incremental test dose over 5 minutes; as above, no other test doses are used.

Drug: Lidocaine-chlorprocaine combination

Interventions

Chlorprocaine DRUG

we aim to examine whether selective nociceptive analgesia can be obtained in epidural analgesia for women in labor by using a combination of lidocaine (opens TPRV-1 and TPRA-1 channels) and chlorprocaine (polarized local anesthetic)

Chlorprocaine only

Lidocaine DRUG

Study participants will receive lidocaine alone

lidocaine alone

Lidocaine-chlorprocaine combination DRUG

study participants randomized to this study arm will receive a a 50:50 mixture of both drugs - where all drugs are administered in concentrations based on their ED50 doses, together with epidural opioids (fentanyl)

Lidocaine-chlorprocaine combination

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Nulliparity
• Early active labor, cervical dilatation less than 5 cm,
• Age between 18 to 40,
• American Society of Anesthesiologists physical status class II
• Body weight less than 110 kg,
• Gestational age greater than 36 completed weeks,
• Singleton pregnancy
• Vertex presentation.

You may not qualify if:

• Narcotic administration in the previous 3 hours
• Previous uterine surgery
• Pre-eclampsia
• Inability to adequately understand the consent

Sponsors & Collaborators

• Hadassah Medical Organization: lead

Study Sites (1)

Hadassah Hebrew University Medical Center, POB 12000

Jerusalem, 91120, Israel

Location

MeSH Terms

Conditions

Labor Pain; Pain; Agnosia

Interventions

chloroprocaine; Lidocaine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

Yehuda Ginosar, MS

CONTACT

0507874388; ginosar@mail.huji.ac.il

Atara Davis

CONTACT

+972533321329; ataratdavis@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 8, 2024
• Study Start: March 1, 2024
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

IL (1)