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ED90 of 3% Chloroprocaine for Cervical Cerclage

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ClinicalTrials.gov Identifier: NCT03805438
Recruitment Status : Completed
First Posted : January 15, 2019
Results First Posted : September 1, 2021
Last Update Posted : October 12, 2021
Sponsor:
Collaborator:
University of Arkansas
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE January 11, 2019
First Posted Date  ICMJE January 15, 2019
Results First Submitted Date  ICMJE August 5, 2021
Results First Posted Date  ICMJE September 1, 2021
Last Update Posted Date October 12, 2021
Actual Study Start Date  ICMJE February 7, 2019
Actual Primary Completion Date October 23, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2021)
The Dose of Intrathecal (IT) Chloroprocaine That Provides Effective Anesthesia in 90% of Patients Undergoing Elective Cerclage Placement (Intraoperative Analgesic Supplementation Not Required). [ Time Frame: 60 minutes ]
Identification of the dose of intrathecal 3% chloroprocaine that will provide adequate anesthesia for a cervical cerclage to occur.
Original Primary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
The dose of intrathecal (IT) chloroprocaine that provides effective anesthesia in 90% of patients undergoing elective cerclage placement (intraoperative analgesic supplementation not required). [ Time Frame: 60 minutes ]
Identification of the dose of intrathecal 3% chloroprocaine that will provide adequate anesthesia for a cervical cerclage to occur.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2021)
  • Maximum Pain Numerical Pain Rating Scale (NPRS) During Surgery (as Reported by Patient, Scored From 0-10 in the PACU). [ Time Frame: 60 minutes ]
    The scale from 0-10 is used where a score of 0 represents no pain at all and a score of 10 represents the worst pain a participant could imagine. It is reported as a single score at a single point in time. No subscales are used.
  • Number of Participants Who Reported Nausea (Self-reported by Patient, Yes or no). [ Time Frame: 60 minutes ]
    Number of participants reporting nausea.
  • Number of Participants With Observed Vomiting. (Observed Yes or no). [ Time Frame: 60 minutes ]
    Number of participants with observed vomiting.
  • Number of Participants Reporting Itching. (Self-reported by Patient, Yes or no). [ Time Frame: 60 minutes ]
    Number of participants reporting itching.
  • Number of Patients Who Were Given Vasopressor Phenylephrine (and Ephedrine) BP Drops Greater Than 15% Below Baseline or < 100mg Hg Systolic. [ Time Frame: 60 minutes ]
  • The Average Dose of Phenylephrine Given to Those Patients Whose BP Dropped Greater Than 15% Below Baseline or < 100mg Hg Systolic. [ Time Frame: 60 minutes ]
    All patients were analyzed for possible requirement of this intervention, though all participants did not require the intervention.
  • Overall Patient Satisfaction at Time of PACU Discharge. [ Time Frame: 60 minutes ]
    The scale used is 0-10 where 0 would represent completely unsatisfied and 10 would be completely satisfied. A 10 would imply that if a participant had to have the procedure performed again, it would be repeated in the exact same fashion it was carried out the first time. This will be assessed at the time of PACU discharge and will be asked one time. No subscales are used.
  • Time to Resolution of Motor Block at End of the Cerclage Placement (Measured in the PACU). [ Time Frame: 60 minutes ]
    The motor block is assessed using the Bromage scale (1-5). The block is objectively assessed using this scale based on which joints a patient is able to mobilize following epidural or subarachnoid block. A score of 1 represents a patient who is unable to mobilize any lower extremity joint. A score of 5 represents a patient able to mobilize all lower extremity joints.
  • Time to Hospital Discharge as Measured as the Time Difference Between Local Anesthetic Injection and Discharge Time as Recorded in the Medical Notes [ Time Frame: approximately 180 minutes ]
  • Time From Spinal Block to Ambulation [ Time Frame: up to 180 minutes ]
  • Time From Spinal Block to Micturition [ Time Frame: approximately 180 minutes ]
  • Time to Complete Sensory Regression [ Time Frame: up to 180 minutes ]
  • Time to Resolution of Motor Block (Bromage Score of 5) [ Time Frame: up to 180 minutes ]
    The motor block is assessed using the Bromage scale (1-5). The block is objectively assessed using this scale based on which joints a patient is able to mobilize following epidural or subarachnoid block. A score of 1 represents a patient who is unable to mobilize any lower extremity joint. A score of 5 represents a patient able to mobilize all lower extremity joints.
  • Time to Readiness for PACU Discharge (Pre-defined Nursing Criteria) [ Time Frame: approximately 180 minutes ]
    Readiness for PACU discharge would include a patient who is able to ambulate unassisted (indicating resolution of motor block), has vital signs within normal limits, has pain levels acceptable to the patient, and has been able to urinate.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2019)
  • Maximum pain Numerical Pain Rating Scale (NPRS) during surgery (as reported by patient, scored from 0-10 in the PACU). [ Time Frame: 60 minutes ]
    The scale from 1-10 is used where a score of 1 represents minimal pain, but some perceptible pain. A score of 10 would represent the worst pain a participant could imagine. It is reported as a single score at a single point in time. No subscales are used.
  • Nausea (self-reported by patient, yes or no). [ Time Frame: 60 minutes ]
  • Vomiting (observed yes or no). [ Time Frame: 60 minutes ]
  • Itching (self-reported by patient, yes or no). [ Time Frame: 60 minutes ]
  • Proportion of patients who were given vasopressor phenylephrine (and ephedrine) BP drops greater than 15% below baseline or < 100mg Hg systolic. [ Time Frame: 60 minutes ]
  • The average dose of phenylephrine given to patients whose BP dropped greater than 15% below baseline or < 100mg Hg systolic. [ Time Frame: 60 minutes ]
  • Overall patient satisfaction at time of PACU discharge. [ Time Frame: 60 minutes ]
    The scale used is 0-10 where 0 would represent completely unsatisfied and 10 would be completely satisfied. A 10 would imply that if a participant had to have the procedure performed again, it would be repeated in the exact same fashion it was carried out the first time. This will be assessed at the time of PACU discharge and will be asked one time. No subscales are used.
  • Motor block at end of the cerclage placement (measured in the PACU). [ Time Frame: 60 minutes ]
    The motor block is assessed using the Bromage scale (1-5). The block is objectively assessed using this scale based on which joints a patient is able to mobilize following epidural or subarachnoid block. A score of 1 represents a patient who is unable to mobilize any lower extremity joint. A score of 5 represents a patient able to mobilize all lower extremity joints.
  • Time to hospital discharge as measured as the time difference between local anesthetic injection and discharge time as recorded in the medical notes [ Time Frame: 180 minutes ]
  • Time from spinal block to ambulation [ Time Frame: 180 minutes ]
  • Time from spinal block to micturition [ Time Frame: 180 minutes ]
  • Time to complete sensory regression [ Time Frame: 180 minutes ]
  • Time to resolution of motor block (Bromage score of 0) [ Time Frame: 180 minutes ]
  • Time to readiness for PACU discharge (pre-defined nursing criteria) [ Time Frame: 180 minutes ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ED90 of 3% Chloroprocaine for Cervical Cerclage
Official Title  ICMJE Determining the ED90 for Intrathecal 3% Chloroprocaine for Elective Cervical Cerclage Surgery
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
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.

Masking: None (Open Label)
Masking Description:
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.
Primary Purpose: Diagnostic
Condition  ICMJE Cerclage, Cervical
Intervention  ICMJE Drug: Chloroprocaine Hcl 3% Inj

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.

Study Arms  ICMJE Experimental: Chloroprocaine dose

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.

Intervention: Drug: Chloroprocaine Hcl 3% Inj
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 6, 2021)
47
Original Estimated Enrollment  ICMJE
 (submitted: January 14, 2019)
40
Actual Study Completion Date  ICMJE October 23, 2020
Actual Primary Completion Date October 23, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03805438
Other Study ID Numbers  ICMJE Pro00100699
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD will be shared between institutions insofar as it is required for the sequential study design when evaluating the primary outcome. The dose of chloroprocaine used for each procedure as well as the outcome of the surgery will dictate the dosing for the next patient at either institution. PHI will not be shared however.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: Analytic Code
Time Frame: The study protocol will be shared between institutions and will be identical. The SAP, CSR, and analytic code is also shared and identical. The ICF however will be different and each institution will use its own version of the consent form.
Access Criteria: Shared data will be stored in REDCap to be used between institutions. The data will be shared by the PIs and all members listed on the Duke IRB submission both at Duke and UAMS. All statistical analyses will be done at Duke.
Current Responsible Party Duke University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Duke University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE University of Arkansas
Investigators  ICMJE
Principal Investigator: Ashraf Habib, MBBS Duke University Hospital
PRS Account Duke University
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP