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Liposomal Bupivacaine After Cesarean Delivery

Sponsor
Wright State University (Other)
Overall Status
Withdrawn
CT.gov ID
NCT03907813
Collaborator
(none)
0
Enrollment
1
Location
2
Arms
15
Anticipated Duration (Months)
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to determine if local wound infiltration with liposomal bupivacaine at the time of cesarean delivery can decrease opioid use and provide adequate post-operative pain control.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Specific Aim 1: To identify the effect of local infiltration of all wound layers with liposomal bupivacaine on opioid consumption up to 48 hours after cesarean delivery.

For this aim, in-patient narcotic use, measured in morphine equivalents, will be documented by the nurses and totaled during each 24 hour period after cesarean section until discharge.

Specific Aim 2: To identify the effect of local infiltration of all wound layers with liposomal bupivacaine on other, relevant, clinical outcomes, including time to first opiate use, time to mobility, occurrence of vomiting, use of rescue antiemetic medications, pain scores, and use of additional measures for pain control such as heating pads, muscle relaxers, gabapentin, between the study groups.

Specific Aim 3: To determine the occurrence of adverse events in the infants of breastfeeding women who have received local infiltration of all wound layers with liposomal bupivacaine compared to breastfeeding women who received saline infiltration.

Study Methods:

Patients will be randomized to either receive 20 mL liposomal bupivacaine diluted to 90 mL (treatment group), or 90 mL normal saline (control group). Patients with a BMI greater than or equal to 40 will receive 150 mL normal saline of the liposomal bupivacaine formulation. Randomization will occur in a 1:1 fashion via Miami Valley Pharmacy staff. All patients will be given the current medications used during cesarean delivery at MVH including Duramorph in the spinal or epidural via the Anesthesia team, Toradol for 24 hours on scheduled followed by Motrin on schedule until discharge.

Instillation of the liposomal bupivacaine or saline will be performed by resident physicians supervised by Wright State or private attending physicians. For each study group, 45 mL of their given solution will be infiltrated into the sub-fascial layer after its closure. Using an 18-gauge needle, 10 mL aliquots will be instilled into each lateral edge and six 2-mL aliquots into the superior and inferior fascial edges.

Post-operative care will first take place in the PACU in the usual fashion according to the anesthesiologist. The anesthesiologists will be blinded to the study group and patients will be given rescue parenteral opioids as deemed necessary.

The primary outcome of this study will be total oral morphine equivalents at 48 hours from the time of surgery. Nurses blind to the study group will record the total amount of opioid medications each patient used. This will be converted to a morphine equivalent of 1mg oral oxycodone to 1.5mg oral morphine.

Selection of Patients:

Recruitment: Patients will be recruited from Miami Valley Hospital Labor and Delivery and from Five Rivers Center for Women's Health. Investigators will identify potential patients from those who are admitted to Labor and Delivery for a scheduled cesarean delivery. Investigators will explain the study to potential patients and will obtain written informed consent from patients who agree to participate in the study.

Data Management Data required for the study will be recorded in the medical record by physicians and nursing staff. Physicians will document the procedure for infiltration in operative notes, indicating that the patient was randomized to "active medication (Experel ®) or saline." MVH Pharmacy staff will record the randomization/treatment key. Investigators, nursing staff, and patients will be blinded to the medication given. Documentation of pain scores, opioid medications used, other pain control methods used (heating pads, muscle relaxers, gabapentin, etc.) will be done by the physicians and nursing staff according to standard procedures. Data collection will consist of medical record review to record data on the paper data collection forms.

Confidentiality of Data PHI will be limited to information needed for the study objectives. Patients will be assigned a study ID number on the paper data collection forms and in the spreadsheet. Patient name and MRN will be kept in a separate key that will allow re-identification only if necessary to complete data collection.

Risks:

There is a risk of a breach of confidentiality. Risks to the Mother: Liposomal bupivacaine (Exparel ®). Liposomal bupivacaine is FDA approved for use via wound infiltration for post-surgical pain control. The most common adverse events include nausea, constipation, and vomiting. There have been reports of adverse neurologic reactions with the use of local anesthetics. These include persistent anesthesia and paresthesia. CNS reactions are characterized by excitation and/or depression. Toxic blood concentrations depress cardiac conductivity and excitability which may lead to dysrhythmias, sometimes leading to death. Allergic-type reactions (e.g., anaphylaxis and angioedema) are rare and may occur as a result of hypersensitivity to the local anesthetic or to other formulation ingredients. There have been reports of chondrolysis (mostly in the shoulder joint) following intra-articular infusion of local anesthetics, which is an unapproved use. Cases of methemoglobinemia have been reported with local anesthetic use. 12 In a Cochrane Review of 20 studies that used local anesthetic wound infiltration after cesarean delivery, no adverse cardiovascular or central nervous system reactions were noted in any of the included studies. 9

Risks to the Infant: Liposomal bupivacaine is contraindicated in pregnant women. Therefore, the use of this medication will occur after the fetus is delivered. Liposomal bupivacaine and its metabolite, pipecoloxylidide, are noted to be present in breastmilk in small amounts. There is no available information on effects of the drug in the breastfed infant or effects of the drug on milk production. The Infant Risk Center has indicated that it is highly unlikely for plasma levels in the infant to reach a toxic level due to any exposure from breastmilk and suggests that use of liposomal bupivacaine is probably compatible with breastfeeding without restriction. 3

Potential Benefits: Patients may receive benefit from the study by experiencing better postoperative pain control or by reducing opiate medication use while maintaining acceptable pain control. The potential benefit to women in the future is to have an effective option for pain control after cesarean delivery that does not require opiate medications.

Statistical Considerations: Based on a previous study performed at this institution in a similar patient population the investigators anticipate a 25% reduction in total oral morphine equivalents at 48 hours. Using a power of 0.80 and an alpha of 0.05 the investigators will need 54 patients per group, or a total of 108 patients in order to detect a difference of this size.

Data Analysis: Analysis of the data will be performed by members of the investigative team using SPSS. Repeated measures ANOVA will be used to compare pain pill (non-opioid) use, opioid pain pill use (in morphine equivalents) and pain scores over time for the study groups. Additional post hoc t-tests will be used as needed to identify specific group differences at the individual time points as appropriate. Potential covariates including parity, previous cesarean delivery, previous surgical history, and BMI will be examined for impact on opioid pain pill use and pain scores. Frequencies for adverse events in infants will be used to identify the occurrence of adverse events in infants exposed to liposomal bupivacaine versus those not exposed (including those who were not breastfed and those who were breastfed among mothers receiving the saline infiltration).

Study Design

Study Type:
Interventional
Actual Enrollment :
0 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Randomized, controlled, double blind trialRandomized, controlled, double blind trial
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double blind
Primary Purpose:
Treatment
Official Title:
The Effect of Local Infiltration of Liposomal Bupivacaine on Opioid Consumption at Time of Cesarean Delivery: A Randomized Controlled Trial
Anticipated Study Start Date :
May 1, 2019
Anticipated Primary Completion Date :
Jun 30, 2020
Anticipated Study Completion Date :
Jul 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: liposomal bupivacaine infiltration

Local infiltration of all wound layers with liposomal bupivacaine (Exparel(R)) 20 ml diluted with 70 ml of normal saline to 90 ml for patient with a BMI of 39 and under. If BMI is 40 or more the 20 ml of liposomal bupivicaine will be diluted to 150 ml by adding 130 ml of normal saline

Drug: Exparel
liposomal bupivacaine wound infiltration
Other Names:
  • liposomal bupivacaine

    		•
    Placebo Comparator: Saline infiltration

    Local infiltration of all wound layers with saline, using to match the amount. The amount of total fluid is divided into 4 and instilled with 1-2 ml at a time in between fascial layers after fascial closure. Each 1/4 will be instilled laterally (2) and on each side of the incision(2)- extra fluid is placed subcutaneously.

    Other: Saline infiltration
    saline wound infiltration

    Outcome Measures

    Primary Outcome Measures

    1. Opioid (narcotic medication) use [at the end of 48 hours after delivery]

      total opioid use, as morphine equivalents; sum of narcotic pain medications over 48 hours reported in morphine equivalents, by the Ohio Automated RX reporting system calculator, where hydrocodone 5 mg is 5 morphine equivalent dose (MED) and percocet 5 is 7.5 MED

    Secondary Outcome Measures

    1. Average pain scores Day 1 [at the end of 24 hours after delivery]

      Patient reported pain scores (0-10 where ten is the highest possible and 0 is no pain) as recorded by nursing staff, average post delivery in recovery and up to 23 hours and 59 minutes.

    2. Average pain scores Day 2 [at the end of 48 hours after delivery]

      Patient reported pain scores (0-10 where ten is the highest possible and 0 is no pain) as recorded by nursing staff, average from 24 hours to 48 hours.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Are between 18 and 45 years of age, inclusive.

    • Are undergoing a planned, primary or repeat, cesarean delivery without permanent sterilization.

    • Have a BMI ≤ 60.

    • Are able to read and understand English.

    Exclusion Criteria:

    • Have pre-eclampsia with severe features.

    • Has been taking medication assisted treatment for opioid addiction during this pregnancy.

    • Have known sensitivity to local anesthetic.

    • Have a known sensitivity to non-steroidal anti-inflammatory medications.

    • Planning to have a tubal ligation after the cesarean delivery.

    • Are unable to receive neuraxial analgesia and/or Duramorph, a morphine formulation that is the standard of care for intrathecal anesthesia at MVH.

    • Are prisoners.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Miami Valley Hospital Dayton Ohio United States 45409

    Sponsors and Collaborators

    • Wright State University

    Investigators

    • Principal Investigator: Marilyn Kindig, DO, Wright State University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Marilyn J Kindig, D.O., Assistant Professor, Wright State University
    ClinicalTrials.gov Identifier:
    NCT03907813
    Other Study ID Numbers:
    • Kindig-Williams-001
    First Posted:
    Apr 9, 2019
    Last Update Posted:
    Jul 31, 2020
    Last Verified:
    Jul 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Pain, Postoperative
    Bupivacaine

    Study Results

    No Results Posted as of Jul 31, 2020