Efficacy of Extended-Release Liposomal Bupivacaine for Post-Partum Pain Management Following Obstetrical Laceration
Condition: Pain, Obstetric
MeSH terms: Labor Pain; Lacerations
Study type: Interventional

Summary: 
      We propose a prospective, randomized, single blinded trial with subjects recruited from the
      WRNMMC Labor and Delivery Unit to study post-partum efficacy of Exparel® for pain control in
      patients undergoing a vaginal delivery who sustained a second, third, or fourth degree
      obstetrical laceration. Subjects who meet inclusion criteria and agree to participate in the
      study will be consented upon admission for active labor or induction of labor and will be
      randomized to receive either 20mL of liposomal bupivacaine or 20ml of 0.25% plain
      bupivacaine, infiltrated through the perineum at completion of their obstetrical repair.
      Current standard of care is to receive no injection of local anesthetic upon completion of
      the repair.

      The primary aim of the trial will be to evaluate post-partum pain using a visual analogue
      pain scale at days 1, 3 and 7 postpartum. All subjects will have acetaminophen, a
      non-steroidal anti-inflammatory drug and narcotic pain medication available for pain control
      regardless of assignment, which is the usual post-partum pain control regimen.

      We anticipate a 30% difference in post-operative pain measurements between the Exparel® group
      and the plain bupivacaine group. Other aims of this study are to evaluate total medication
      usage, comparing the study group to the control, and compare quality of life measures between
      the two study groups.
    

Detailed description: 
      All pregnant female subjects over the age of 18 eligible to deliver vaginally at WRNMMC will
      be screened for potential recruitment in our long-acting liposomal bupivacaine (Exparel®)
      postpartum pain medicine trial prior to admission for active labor or induction of labor. At
      the 36 or 38 week visit, all pregnant patients will receive an information sheet describing
      the study participation and they will be asked to consider participating in the study. At the
      time of admission, patients will be asked if they were provided the study information sheet
      and if they would like to consent to study participation. Discussion of the study will occur
      after the delivery consent form for obstetric services has been signed and when discussion of
      postpartum pain management is addressed. Those subjects who meet inclusion criteria for the
      study will be randomized to either the plain bupivacaine group or exparel group after vaginal
      delivery and identification of a second, third, or fourth degree laceration.

      Potential study subjects will be informed that the purpose of the study is to evaluate the
      efficacy of two different formulations of bupivacaine, 0.25% plain bupivacaine and liposomal
      bupivacaine (Exparel®) on postpartum pain following repair of a second, third, or fourth
      degree laceration sustained during vaginal delivery. This medication is FDA (Food and Drug
      Administration) approved and is currently being used in our hospital by other surgical
      sub-specialties as part of a multi-modal approach to post-operative pain control.

      If a potential subject chooses to participate, she will be randomized to one of two groups,
      either a 0.25% bupivacaine injection of total 20 ml or an injection of total 20 ml
      long-active liposomal bupivacaine that will be injected in the subject's perineum (the tissue
      between the opening of the anus and the vagina) at the completion of the case in the delivery
      room. Regardless of the decision to participate in the study or which treatment group
      assignment, all subjects will have the same options for partum pain medications. There is no
      monetary payment for joining the study and subjects may choose to leave the study at any
      point during the study without consequence. They will still receive the same high standard of
      care from our Service.

      The study is designed as a single blind, randomized study. This means the subject will not
      know which group a subject is assigned to until completion of the study. Subjects may choose
      to have their allocated study arm disclosed at this time. Randomization will occur using a
      computer-generated randomization program carried out in the Investigational Pharmacy by Dr.
      Moussavian. Subjects will be randomly assigned to either receive the study medication or
      bupivacaine.

      The primary goal of the study is to assess how effective the study medication is in providing
      adequate pain control following repair of a second, third, or fourth degree laceration;
      therefore, the subjects' post-partum pain will be assessed at various intervals following the
      repair. On post-partum day one, subjects will be asked questions regarding their pain level
      in the vaginal area according to an 11-point visual pain scale. Subjects will also be asked
      about their bowel movements and any associated pain, again, using the same visual pain scale.
      Subjects will also be asked to the impact the pain has on 4 quality of life measures using an
      11-point visual pain scale. Subjects will also be called or contacted via email thru Relay
      Health on post-op day three and on post-op day seven to assess pain on those days. Part of
      the study's goal is to assess whether the study medication provides pain control for longer
      than the acute (24 hour) period. Subjects will be given a visual pain scale to go home with
      so that they can reference it during their post-operative phone or email follow ups.
      Additionally, subjects will be asked to gather their pain medication bottles in order to
      count out the remaining pills in each bottle. This will allow us to determine the amount of
      oral pain medication used since discharge from the hospital.

      Study participants will review the study consent form in detail with a provider, also an
      Associate Investigator in the study. The subject will be given a copy of the signed consent
      and a copy will remain on file in the patient's hospital record. The data sheet with
      non-identifiable subject number will be the only identifying information on the sheet. The
      subject's demographic data (gravida/parity, age, BMI, past medical history, allergies,
      current medications, history of significant drug or alcohol dependence) will be annotated on
      this data sheet along with the postpartum pain medications she receives. The data sheets will
      be kept in a locked cabinet within the resident library on the Labor and Delivery Unit, in a
      room locked during all-hours. A master list of subjects' full names and sponsor's last four
      of the social security number will be kept in the same location to reference the subjects'
      identification code. The dates of enrollment will be annotated on the master list as well.
      Follow-up phone call dates/email replies will be collected as well. Subjects will be
      re-assured that her participation in the study will be completely confidential and her
      identifying information will be double-locked when not being reviewed.

      Following review of the study and obtaining of a consent form, the pain scale on the visual
      analog pain scale will be reviewed with the subject. Subjects must be willing to speak with a
      member of the study team on post-delivery day one, three, and seven regarding their
      post-operative pain, medications and bowel movements. Completion of day one data will occur
      in the hospital, prior to hospital discharge. The subject will be asked to indicate whether
      they prefer contact via phone or by email, using the Relay Health Network for day three and
      seven. A maximum of three attempts will be made to contact the subject on their designated
      follow up date, between the hours of 0800 and 2000. At the conclusion of the admission
      process, the subject will be reassured that if they desire removal from the study at any
      time, there will be no change in their customary post-delivery care.

      At completion of the repair of the vaginal laceration, the consenting physician will enter
      the appropriate information on the data sheet, including the prescribed medications and
      quantities. A randomization envelope will be opened, assigning the patient to either the
      bupivacaine group or the Exparel group. The appropriate study medication will be obtained
      from the study refrigerator in the resident library and brought to the delivery room. Dr.
      Moussavian will randomize each subject to either Exparel or bupivacaine group, via pre-sealed
      opaque envelopes, and blind three 10mL syringes containing a total of 20 mL of either normal
      saline or liposomal bupivacaine (increments of 9mL, 9mL and 2mL). Syringe barrels will be
      covered with solid white labels to mask syringe contents. She will also print out a label to
      accompany the syringe to the Operating Room on the day of surgery stating:

      "This subject is enrolled in study protocol #_______ and is to receive no additional
      bupivacaine post-operatively for 96 hours. "

      This label will be placed on a wristband, following randomization, and will be worn during
      the entire hospital stay. It will assure that those subjects who receive liposomal
      bupivacaine will not receive additional bupivacaine but will still maintain blinding of all
      involved in the protocol.

      On the day of admission for delivery, a member of the research team will, consent interested
      subjects for study participation. Any last minute questions can be answered and the subject
      will be advised that they can withdraw from the study at any time.

      In the delivery room, the delivery team will identify the laceration and perform a repair,
      using standard technique. The use of 1% lidocaine with epinephrine may be used as a
      distention media to assist with pain relief during the repair so long as a minimum of 20
      minutes elapses prior to injection of the study medication or bupivacaine. Once a laceration
      has been identified, a research team member will leave the room and obtain a randomization
      envelope from the locked study medication refrigerator in the residents' office. The envelope
      will be opened; identifying which treatment arm the patient will be assigned. The team member
      will come back to the room and tell the delivery nurse to leave the room and draw up the
      study medication into 20ml blinded-syringe. Once all surgical procedures have been completed,
      the circulating room nurse will verify the subject's name and date of birth and hand the 20mL
      blinded syringe to the delivering provider, who will attach an injection needle to the
      syringe. The surgeon will identify the bilateral perineal areas to be injected, approximated
      1-2 cm below the opening of the vagina and 1-2 cm on either side of midline. 9 mL of the
      syringe solution will be injected into each bilateral location and then 2 mL at edge of
      vaginal opening (see figure1 below). The injection of the solution will occur at the
      completion of the surgical case. Following administration of the injection, the team will
      resume normal post-procedure care. The operating surgeon will verify the study protocol
      identification sticker has been placed in the subject's paper chart.

      Post-delivery, the subject will recover in the delivery room per WRNMMC protocol and be
      transferred to either the postpartum unit as per routine post-operative criteria. Postpartum
      pain control will be managed by the obstetric team. Further injections of pain medications
      will not be given in the perineal area outside of the operating room.

      On postpartum day one, a member of the obstetric team will visit the subject in order to
      obtain a pain and quality of life rating (0-10) based on the visual analog pain and quality
      of life scales. This will be documented as Day one data. Upon discharge postpartum care
      instructions will be reviewed and the subject will be reminded to expect her follow-up phone
      call or email via Relay Health on day three and seven.

      During postpartum follow up on day 3 and day 7, subjects will be asked to get out their
      visual analog pain scale and rate the pain on their abdomen and the pain in the vagina on a
      0-10 scale. The subject will also be asked if they have had a bowel movement and whether or
      not it was painful, based on the same pain scale 0-10. Subjects will be sent home with a copy
      of the pain scale with the hospital post-operative discharge paperwork. At postpartum phone
      or email contacts, subjects will be asked to count their remaining pain pills and these
      numbers will be documented in the data collection sheet.

      All data sheets will be collected at the completion of each postpartum day and placed in the
      locked cabinet. Obstetric team members will have access to sheets to record data as it is
      collected. The data sheets will be shredded and disposed in a HIPAA compliant receptacle per
      WRNMMC protocol at the completion of the study. All consents and HIPAA authorizations will be
      maintained for six years after the study is closed. The Principal Investigator, Dr.
      Christopher Strauchon, will be available for debriefing of any subject after the study is
      completed if the subject desires.
    

Intervention name(s): Bupivacaine Liposome Injectable Product; 0.25% plain bupivacaine
Intervention type(s): Drug; Drug
Intervention description(s): 20cc of liposomal bupivacaine will be injected into the vaginal/perineal laceration site, once, following completion of the surgical repair.; 20cc of 0.25% plain bupivacaine will be injected into the vaginal/perineal laceration site, once, following completion of the surgical repair.
Other intervention name(s): Exparel
Intervention MeSH terms: Bupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment