ED90 of Epidural Bupivacaine With Lidocaine for the Initiation of Labor Analgesia

ED90 of Epidural Bupivacaine for the Initiation of Labor Analgesia: A Randomized Biased Coin Sequential Allocation Trial With a Lidocaine Test Dose

To estimate the dose of bupivacaine required to achieve initial effective comfort in 90% of patients (ED90) via the epidural (DPE or EPL) technique in women undergoing labor after receiving a lidocaine "test dose"

Study Overview

• Status: Recruiting
• Conditions: Analgesia; Labor Pain
• Intervention / Treatment: Drug: Bupivacaine Hydrochloride

Detailed Description

The primary objective of our study is to use a biased coin up-down allocation methodology to estimate the dose of bupivacaine required to achieve initial effective comfort in 90% of patients (ED90) via the epidural (DPE or EPL) technique in women undergoing labor induction or augmentation; we hypothesize that we will be able to determine the ED90 of bupivacaine for each technique with adequate precision to inform the optimal doses. We will be conducting this study in women who receive a prior lidocaine "test dose" used in standard clinical practice

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lawrence C Tsen, MD; Phone Number: 617-732-8216; Email: ltsen@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Lawrence C Tsen, MD; Phone Number: 617-732-8216; Email: ltsen@zeus.bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Parturient with no major co-morbidities
• Singleton, vertex gestation at term (37-42 weeks)
• Less than or equal to 5 cm dilation
• Desire to receive epidural labor analgesia
• Numerical Rating Scale greater or equal to 5 (NRS 0-10, where 0 = no pain, and 10 = worst pain imaginable), at time of epidural labor analgesia request.

Exclusion Criteria:

• Current or historical evidence of clinically significant disease or condition, including diseases of pregnancy (i.e preeclampsia, gestational diabetes)
• Any contraindication to the administration of an epidural technique
• History of hypersensitivity or idiosyncratic reaction to an amide local anesthetic agent
• Current or historical evidence of a disease which may result in the risk of a cesarean delivery (i.e. history of uterine rupture). NB: Exception-trial of labor after cesarean delivery (TOLAC) will be eligible.
• Evidence of anticipated fetal anomalies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dural Puncture Epidural Technique; Laboring women receiving the Dural Puncture Epidural (DPE) Technique, after a lidocaine "test dose", with dose of Bupivacaine 0.25% diluted to 20 mL with isotonic sterile 0.9% saline. The first subject in the DPE group will receive an initial dose of bupivacaine 25 mg, with an endpoint being the achievement of an NRS < 3 at 30 min. Subsequent patients are administered bupivacaine doses determined by the response of the previous subject, as per the biased coin method. The subsequent up and down interval doses are bupivacaine 2.5 mg (1 mL) increments, with an anticipated dose range from 20 mg to 40 mg.	Drug: Bupivacaine Hydrochloride; Subjects will receive a dose of bupivacaine as described in the arm section of this trial
ACTIVE_COMPARATOR: Epidural Technique; Laboring women receiving the Conventional Epidural Technique (EPL), after receiving a lidocaine "test dose" with dose of Bupivacaine 0.25% diluted to 20 mL with isotonic sterile 0.9% saline. The first subject in the EPL group will receive an initial dose of bupivacaine 25 mg, with an endpoint being the achievement of an NRS < 3 at 30 min. Subsequent patients are administered bupivacaine doses determined by the response of the previous subject, as per the biased coin method. The subsequent up and down interval doses are bupivacaine 2.5 mg (1 mL) increments, with an anticipated dose range from 20 mg to 40 mg.	Drug: Bupivacaine Hydrochloride; Subjects will receive a dose of bupivacaine as described in the arm section of this trial

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal Numerical Pain Rating Score	(0-10, with higher scores meaning more pain); goal with analgesia is < 3/10	30 minutes

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Publications and helpful links

General Publications

• Chau A, Bibbo C, Huang CC, Elterman KG, Cappiello EC, Robinson JN, Tsen LC. Dural Puncture Epidural Technique Improves Labor Analgesia Quality With Fewer Side Effects Compared With Epidural and Combined Spinal Epidural Techniques: A Randomized Clinical Trial. Anesth Analg. 2017 Feb;124(2):560-569. doi: 10.1213/ANE.0000000000001798.
• Ngan Kee WD, Ng FF, Khaw KS, Lee A, Gin T. Determination and comparison of graded dose-response curves for epidural bupivacaine and ropivacaine for analgesia in laboring nulliparous women. Anesthesiology. 2010 Aug;113(2):445-53. doi: 10.1097/ALN.0b013e3181bdf9da.
• Benhamou D, Ghosh C, Mercier FJ. A randomized sequential allocation study to determine the minimum effective analgesic concentration of levobupivacaine and ropivacaine in patients receiving epidural analgesia for labor. Anesthesiology. 2003 Dec;99(6):1383-6. doi: 10.1097/00000542-200312000-00022.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2022
• Primary Completion (ANTICIPATED): October 1, 2024
• Study Completion (ANTICIPATED): October 1, 2024

Study Registration Dates

• First Submitted: September 14, 2022
• First Submitted That Met QC Criteria: September 14, 2022
• First Posted (ACTUAL): September 16, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Local Anesthetic; Bupivacaine; Dural puncture epidural; Neuraxial Analgesia
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Labor Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 2022P002226

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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