Chloroprocaine Lavage to Improve Outcomes Related to Operative Cesarean Delivery (CLOR-PRO)

The long term objective is to show that intraperitoneal chloroprocaine can be used an alternative option to avoid general anesthesia during cesarean delivery, to alleviate mother's discomfort from surgical pain, reduce complications, and improve the birth experience. The objectives in this study are to determine the amount of chloroprocaine that is absorbed into the blood in order to create a plasma concentration time profile and to determine the incidence of side effects to help guide selection of an appropriate concentration for future study.

Study Overview

• Status: Active, not recruiting
• Conditions: Cesarean Section
• Intervention / Treatment: Drug: Preservative free 1% Chloroprocaine; Drug: Preservative free 2% Chloroprocaine; Drug: Preservative free 3% Chloroprocaine

Detailed Description

Compared to general anesthesia, neuraxial anesthesia (spinals and epidurals) is associated with a lower risk for maternal aspiration and airway compromise, exposes the baby to less anesthetic, and allows for greater maternal involvement in the birth process. For these reasons, it has become the preferred method of anesthesia for cesarean delivery. Spinals that are placed to facilitate cesarean delivery have a duration of one to two hours. Currently, if that duration is exceeded patients must have general endotracheal anesthesia. In addition, suboptimal neuraxial anesthesia for cesarean delivery is not uncommon with an incidence of 2-9%, depending upon the urgency of surgery and the type of neuraxial block. Providing less than adequate anesthesia for cesarean delivery may increase the risk of legal liability. For this reason, some patients with suboptimal neuraxial anesthesia have intraoperative conversion to general endotracheal anesthesia.

The first known description of the use of intraperitoneal local anesthetic to provide anesthesia for cesarean delivery was published in 1975. In this article Ranney et al. described how to use up to 100 mL of 1% procaine to provide anesthesia for cesarean delivery under local field block alone. Some of this was injected into the skin and fascia, and the remainder was diluted to 0.5% and "spilled" into the peritoneum.

Multiple publications have shown that intraperitoneal local anesthetic can be used to treat intraoperative and postoperative pain, prevent postoperative nausea, and shorten hospital length of stay. A recently published 40-month case series showed that chloroprocaine lavage can be used as part of a multimodal approach to treating intraoperative pain. In this case series, the technique of chloroprocaine lavage helped investigators to avoid general endotracheal anesthesia in 32 women having a cesarean delivery.

In this case series, no patients exhibited clinical signs of systemic local anesthetic toxicity. It is believed that chloroprocaine has a limited potential for toxicity because of its short plasma half-life, which is only 11-21 seconds. The purpose of this study is to determine the amount of chloroprocaine that is taken up into the blood stream after intraperitoneal administration to ensure that blood levels are low and do not raise a safety concern. Data obtained from this study will help to define a safe dose of chloroprocaine for intraperitoneal administration.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU Labor and Delivery; Oregon Health and Science University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects ≥ 18 to 50 years of age having scheduled cesarean sections on 12C (Labor and Delivery) within Oregon Health & Science University (OHSU).
• Only subjects having spinal anesthesia will be eligible.
• Only subjects that can have a Pfannenstiel incision will be enrolled.

Exclusion Criteria:

• Subjects with chronic narcotic usage
• Subjects that are deemed to need a combined spinal epidural for any reason.
• Subjects who are unable to successfully get a spinal block
• Subjects with known atypical cholinesterase activity
• American Society of Anesthesiologist physical status IV or higher
• Subjects with contraindication to neuraxial anesthesia (coagulopathy, infection)
• Subjects with stage 4 chronic kidney disease or worse (eGFR < 30 ml/min)
• Subjects with significant hepatic dysfunction (AST or ALT > 2x the upper limit of normal)
• Subjects with allergies to drugs required for this protocol.
• Subjects with multifetal gestations
• Subjects with a BMI > 40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Preservative free Chloroprocaine Group 1; 40 ml of preservative-free 1% chloroprocaine	Drug: Preservative free 1% Chloroprocaine; 40 ml of preservative-free 1% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.; Other Names: Nesacaine
ACTIVE_COMPARATOR: Preservative free Chloroprocaine Group 2; 40 ml of preservative-free 2% chloroprocaine	Drug: Preservative free 2% Chloroprocaine; 40 ml of preservative-free 2% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.; Other Names: Nesacaine
ACTIVE_COMPARATOR: Preservative free Chloroprocaine Group 3; 40 ml of preservative-free 3% chloroprocaine	Drug: Preservative free 3% Chloroprocaine; 40 ml of preservative-free 3% chloroprocaine is planned for administration into the peritoneal cavity after delivery of the baby.; Other Names: Nesacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chloroprocaine plasma concentration at 1 minute	The chloroprocaine plasma concentration obtained from a venous sample 1 minute after intraperitoneal chloroprocaine administration.	1 minute after intraperitoneal chloroprocaine administration
Chloroprocaine plasma concentration at 5 minutes	The chloroprocaine plasma concentration obtained from a venous sample 5 minutes after intraperitoneal chloroprocaine administration.	5 minutes after intraperitoneal chloroprocaine administration
Chloroprocaine plasma concentration at 10 minutes	The chloroprocaine plasma concentration obtained from a venous sample 10 minutes after intraperitoneal chloroprocaine administration.	10 minutes after intraperitoneal chloroprocaine administration
Chloroprocaine plasma concentration at 20 minutes	The chloroprocaine plasma concentration obtained from a venous sample 20 minutes after intraperitoneal chloroprocaine administration.	20 minutes after intraperitoneal chloroprocaine administration
Chloroprocaine plasma concentration at 30 minutes	The chloroprocaine plasma concentration obtained from a venous sample 30 minutes after intraperitoneal chloroprocaine administration.	30 minutes after intraperitoneal chloroprocaine administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Adverse experience reporting will include the following: seizures, tinnitus, metallic taste, anxiety, agitation, muscle twitching, drowsiness, respiratory depression, dizziness, nausea, vomiting, vision changes, paresthesias, perioral numbness, hypotension, arrhythmias, and cardiac arrest.	Within 4 hours of intraperitoneal chloroprocaine administration

Collaborators and Investigators

• Sponsor: Oregon Health and Science University

Publications and helpful links

General Publications

• Ranney B, Stanage WF. Advantages of local anesthesia for cesarean section. Obstet Gynecol. 1975 Feb;45(2):163-7.
• Togioka BM, Zarnegarnia Y, Bleyle LA, Koop D, Brookfield K, Yanez ND, Treggiari MM. Pharmacokinetics and Tolerability of Intraperitoneal Chloroprocaine After Fetal Extraction in Women Undergoing Cesarean Delivery. Anesth Analg. 2022 Oct 1;135(4):777-786. doi: 10.1213/ANE.0000000000006064. Epub 2022 May 11.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 30, 2019
• Primary Completion (ACTUAL): September 17, 2020
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 29, 2018
• First Posted (ACTUAL): November 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 20, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: lavage; cesarean delivery; chloroprocaine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Chloroprocaine; Procaine
• Other Study ID Numbers: 19021

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.: Yes