Clinical trial NCT03805438: ED90 of 3% Chloroprocaine for Cervical Cerclage
Official title: Determining the ED90 for Intrathecal 3% Chloroprocaine for Elective Cervical Cerclage Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cerclage, Cervical
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: University of Arkansas
First posted: 2019-01-15
Enrollment: 47
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Initial Patient (A#X) 45mg (1.5mL) of Chloroprocaine 3% (Nesacaine - Fresenius Kabi), will be drawn up into a 3 ml syringe (a 1 ml 'TB syringe' will be used to aspirate the drug in aliquots to ensure accuracy). The following additive will be added: 10 mcg (0.2ml) of fentanyl (50 mcg/ml) 0.3 ml of sterile 0.9% sodium chloride Thus the total volume in the syringe will be 2 ml. Study drugs will be prepared by one anesthesiologist (un-blinded) and administered by another anesthesiologist (blinded).

Subsequent Patient (A#X+1) The dose of Chloroprocaine 3% based on outcome from prior subject and calculations mentioned previously will be added to 10 mcg (0.2ml) of fentanyl (50 mcg/ml). Sterile 0.9% sodium chloride will be added until the total volume in the syringe is 2 ml.
Primary purpose: DIAGNOSTIC

Brief summary: The aim of this study is to identify the dose of intrathecal (IT) chloroprocaine that provides effective anesthesia in 90% of patients undergoing elective cerclage placement (intraoperative analgesic supplementation not required).

Detailed description: Cervical cerclage is a procedure performed on pregnant women with cervical incompetence to reduce the risk of second trimester spontaneous abortion and preterm labor. This outpatient procedure is performed commonly under both general and regional anesthesia. In an effort to ensure rapid discharge some institutions prefer the use of general anesthesia; however, this has the disadvantage of exposing the fetus to general anesthetic drugs, increased risk of aspiration and a higher requirement for opioid analgesia post operatively. The benefits of neuraxial anesthesia for cerclage placement includes rapid onset of a dense sensory block, reduced fetus exposure to medications, and maintenance of maternal airway reflexes. Successful analgesia for cerclage placement requires a sensory block from S4-T10 dermatomes. Inadequate sensory coverage with a spinal anesthetic typically necessitates the conversion to general anesthesia adding risk to the mother and fetus while increasing intraoperative times and resources. Currently there are no studies determining optimum dose of spinal chloroprocaine for cervical cerclage. The investigators propose a dose determining study to determine the ED90 of intrathecal lidocaine and chloroprocaine which will help decrease incidence of inadequate anesthesia for cervical cerclage.

This is a multicenter, double blinded, dose ranging, biased-coin design study. Usual practice for regional anesthesia for cerclage placement consists of a mixture of 3% chloroprocaine and fentanyl. The exact dosing of the local anesthetic mixture used is dependent on the anesthesiologist's preference. Chloroprocaine provides a rapid onset of surgical anesthesia with little need for intraoperative analgesic supplementation. If there are contraindications for spinal anesthesia or patient refusal than general anesthesia is offered as an alternative.

The aim of this study is to assess the anesthetic quality of various doses chloroprocaine and in elective cerclage placement. Chloroprocaine is licensed and commonly administered intrathecally for cerclage placement.

To mitigate against the occurrence of inadequate analgesia in this ED90 study, a combined spinal-epidural technique will be utilized in order to provide supplemental analgesia via epidural top up if needed.

The investigators propose testing the hypothesis in patients scheduled for elective cervical cerclage placement. Participants will receive standard of care for anesthesia but in the context of a clinical trial with the addition of randomization, blinding, and more comprehensive evaluation of the trial outcomes (see outcomes objectives below).

The proposed study will be conducted over a 2 year period from January 2019 to September 2020.

Spinal Study Solutions The solutions and their administration procedures are identical to those used outside this research and are almost exclusively used for patients requiring spinal anesthesia for cervical cerclage. The only deviation involves diluting the chloroprocaine with saline so that study solutions are of equal volume to maintain blinding.

Initial Patient (A#X) 45mg (1.5mL) of Chloroprocaine 3% (Nesacaine - Fresenius Kabi), will be drawn up into a 3 ml syringe (a 1 ml 'TB syringe' will be used to aspirate the drug in aliquots to ensure accuracy). The following additive will be added: 10 mcg (0.2ml) of fentanyl (50 mcg/ml) 0.3 ml of sterile 0.9% sodium chloride Thus the total volume in the syringe will be 2 ml. Study drugs will be prepared by one anesthesiologist (un-blinded) and administered by another anesthesiologist (blinded).

Subsequent Patient (A#X+1) The dose of Chloroprocaine 3% based on outcome from prior subject and calculations mentioned previously will be added to 10 mcg (0.2ml) of fentanyl (50 mcg/ml). Sterile 0.9% sodium chloride will be added until the total volume in the syringe is 2 ml.

Rescue If the subject has discomfort and requests analgesia, then 5 ml of 3% chloroprocaine via the epidural route will be given, alternatively the anesthesiologist can treat the discomfort at his discretion. Other alternatives include intravenous fentanyl, ketamine, inhalational nitrous oxide and conversion to general anesthesia.

Riks/Benefit Risks of the procedure include the following: discomfort during placement (10% or 1 in 10), drop in blood pressure (1% or 1 in 100), headache (1% or 1 in 100), allergic reactions (0.001% or 1 in 100,000), bleeding or infection (0.001% or 1 in 100,000), damage to nerves (0.001% or 1 in 100,000), failure of the anesthetic or inadequate anesthesia and need for general anesthesia (0.1% or 1 in 1,000). The benefit of participating in the study is that perceived pain may be better controlled, however this cannot be guaranteed.

This study will be conducted at two study sites, the University of Arkansas for Medical Sciences in Little Rock, Arkansas and Duke University in Durham, North Carolina.

Eligibility criteria: Inclusion Criteria:

* ≥ 18 years of age
* Singleton pregnancy
* ASA class II or III
* Cervical cerclage 1st or 2nd trimester of pregnancy
* Simple prophylactic cervical cerclage

Exclusion Criteria:

* Patient refusal
* Abdominal and complex cervical cerclage (e.g. bulging bag)
* BMI ≥ 50 kg/m2
* ASA class IV or above
* Contraindication to neuraxial anesthesia
* Allergy to chloroprocaine

Primary outcomes:
measure: The Dose of Intrathecal (IT) Chloroprocaine That Provides Effective Anesthesia in 90% of Patients Undergoing Elective Cerclage Placement (Intraoperative Analgesic Supplementation Not Required).
timeFrame: 60 minutes
Secondary outcomes:
measure: Maximum Pain Numerical Pain Rating Scale (NPRS) During Surgery (as Reported by Patient, Scored From 0-10 in the PACU).
timeFrame: 60 minutes
measure: Number of Participants Who Reported Nausea (Self-reported by Patient, Yes or no).
timeFrame: 60 minutes
measure: Number of Participants With Observed Vomiting. (Observed Yes or no).
timeFrame: 60 minutes
measure: Number of Participants Reporting Itching. (Self-reported by Patient, Yes or no).
timeFrame: 60 minutes
measure: Number of Patients Who Were Given Vasopressor Phenylephrine (and Ephedrine) BP Drops Greater Than 15% Below Baseline or < 100mg Hg Systolic.
timeFrame: 60 minutes
measure: The Average Dose of Phenylephrine Given to Those Patients Whose BP Dropped Greater Than 15% Below Baseline or < 100mg Hg Systolic.
timeFrame: 60 minutes
measure: Overall Patient Satisfaction at Time of PACU Discharge.
timeFrame: 60 minutes
measure: Time to Resolution of Motor Block at End of the Cerclage Placement (Measured in the PACU).
timeFrame: 60 minutes
measure: Time to Hospital Discharge as Measured as the Time Difference Between Local Anesthetic Injection and Discharge Time as Recorded in the Medical Notes
timeFrame: approximately 180 minutes
measure: Time From Spinal Block to Ambulation
timeFrame: up to 180 minutes
measure: Time From Spinal Block to Micturition
timeFrame: approximately 180 minutes
measure: Time to Complete Sensory Regression
timeFrame: up to 180 minutes
measure: Time to Resolution of Motor Block (Bromage Score of 5)
timeFrame: up to 180 minutes
measure: Time to Readiness for PACU Discharge (Pre-defined Nursing Criteria)
timeFrame: approximately 180 minutes
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
Study officials:
affiliation: Duke University Hospital
name: Ashraf Habib, MBBS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharawi N, Tan HS, Taylor C, Fuller ME, Landreth RA, Diomede OI, Williams M, Martinello C, Mhyre JM, Habib AS. ED 90 of Intrathecal Chloroprocaine With Fentanyl for Prophylactic Cervical Cerclage: A Sequential Allocation Biased-Coin Design. Anesth Analg. 2022 Apr 1;134(4):834-842. doi: 10.1213/ANE.0000000000005927.