nctId: NCT06302257 id: 0532-23-HMO briefTitle: Randomized Controlled Trial of Combined Lidocaine - Chlorprocaine in Labor Epidural Analgesia. overallStatus: NOT_YET_RECRUITING date: 2024-03-01 date: 2025-03-01 date: 2025-03-01 date: 2024-03-08 date: 2024-03-12 name: Hadassah Medical Organization class: OTHER briefSummary: 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 studyType: INTERVENTIONAL phases: PHASE4 allocation: RANDOMIZED interventionModel: SINGLE_GROUP primaryPurpose: HEALTH_SERVICES_RESEARCH masking: TRIPLE whoMasked: PARTICIPANT whoMasked: CARE_PROVIDER whoMasked: INVESTIGATOR count: 60 type: ESTIMATED name: Chlorprocaine name: Lidocaine name: Lidocaine-chlorprocaine combination measure: VAS pain score / modified Bromage motor block score measure: Segmental sympathectomy measure: Sensory assessment to cold sensation measure: Anesthesia requirement. measure: Pushing ability in labor. measure: Maternal Blood pressure sex: FEMALE minimumAge: 18 Years maximumAge: 40 Years stdAges: ADULT facility: Hadassah Hebrew University Medical Center, POB 12000 city: Jerusalem zip: 91120 country: Israel lat: 31.76904 lon: 35.21633 hasResults: False