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Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block for Pain Control After Vaginal Reconstructive Surgery

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ClinicalTrials.gov Identifier: NCT03040011
Recruitment Status : Completed
First Posted : February 1, 2017
Results First Posted : March 9, 2020
Last Update Posted : March 9, 2020
Sponsor:
Collaborator:
Magee-Womens Research Institute
Information provided by (Responsible Party):
Lauren Giugale, MD, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE January 25, 2017
First Posted Date  ICMJE February 1, 2017
Results First Submitted Date  ICMJE February 7, 2020
Results First Posted Date  ICMJE March 9, 2020
Last Update Posted Date March 9, 2020
Actual Study Start Date  ICMJE June 1, 2017
Actual Primary Completion Date April 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 7, 2020)
Primary Postoperative Pain Measured by the Numerical Rating Scale (NRS) [ Time Frame: 24 hours postoperatively ]
Postoperative pain measured by the numerical rating scale (NRS) at 24 hours postoperatively. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
Primary Postoperative Pain Measured by the Numerical Rating Scale (NRS) [ Time Frame: 24 hours postoperatively ]
Postoperative pain measured by the numerical rating scale (NRS) at 24 hours postoperatively.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 6, 2020)
  • 6 Hour Postoperative Pain Measured by the NRS [ Time Frame: 6 hours postoperatively ]
    Postoperative pain as measured by the NRS at 6 hours after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain. Of note, there is a typographical error in the protocol section and refers to this outcome as a NRS score at 3 hours postoperatively. The final IRB approved protocol is a 6 hour postoperative timepoint and this is the correct outcome reported here in the results section.
  • POD 2 Postoperative Pain Measured by the NRS [ Time Frame: 2 days after surgery ]
    Postoperative Pain Measured by the NRS 2 days after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
  • POD 3 Postoperative Pain Measured by the NRS [ Time Frame: 3 days after surgery ]
    Postoperative Pain Measured by the NRS 3 days after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
  • 1 Week Postoperative Pain Measured by the NRS [ Time Frame: 1 week after surgery ]
    Postoperative Pain Measured by the Numeric Rating Scale 1 week after surgery. The Numeric Rating Scale is an 11 point scale ranging from 0-10 with higher scores indicating worse pain.
  • Proportion of Patients With Same Day Discharge [ Time Frame: Day of surgery ]
    Same day discharge was defined as a patient being discharged on the same day as surgery and did not require an admission after surgery. The proportion of patients who were discharged on the day of surgery was compared between groups.
  • Postoperative Urinary Retention [ Time Frame: 0-24 hours postoperatively ]
    Urinary retention was defined as the need to perform self-catheterization or have an indwelling catheter placed postoperatively. The proportion of patients with urinary retention was compared between groups.
  • Adverse Events [ Time Frame: 0-12 weeks postoperatively ]
    The number of adverse events in each study group was assessed and compared between study groups. An adverse event was described as any medical or surgical complication that occurred either intraoperatively or postoperatively.
  • Nausea and Vomiting Measured by the PONV Scale [ Time Frame: 6 hours postoperatively ]
    Intensity of postoperative nausea and vomiting (PONV) measured by the PONV scale prior to discharge. The Postoperative Nausea and Vomiting Intensity Scale is a four-question assessment to measure clinically significant nausea and vomiting with a range from 0-7 with higher scores signifying more clinically significant nausea and vomiting.
  • Anti-emetic Consumption [ Time Frame: 3 hours postoperatively ]
    The amount of inpatient anti-emetic consumption, recorded in number of doses of nausea medication
  • Return to Baseline Activities Using the Activities Assessment Scale [ Time Frame: 1 week postoperative ]
    Resumed normal daily activities using the Activities Assessment Scale (AAS) by 1 week after surgery. The AAS is a 13-point scale on which patients rate their difficulty performing a range of activities from "No difficulty" to "Not able to do it." A final score ranging from 0-100 is transformed, with higher numbers reflecting less difficulty with activities. We defined return to normal as when a patient's postoperative AAS scores was at or greater than the baseline AAS score. We report the proportion of patients in each study arm who returned to baseline activity at each timepoint.
  • Return to Baseline Activities Using the Activities Assessment Scale [ Time Frame: 2 week postoperative ]
    Resumed normal daily activities using the Activities Assessment Scale (AAS) by 2 weeks after surgery. The AAS is a 13-point scale on which patients rate their difficulty performing a range of activities from "No difficulty" to "Not able to do it." A final score ranging from 0-100 is transformed, with higher numbers reflecting less difficulty with activities. We defined return to normal as when a patient's postoperative AAS scores was at or greater than the baseline AAS score. We report the proportion of patients in each study arm who returned to baseline activity at each timepoint.
  • Return to Baseline Activities Using the Activities Assessment Scale [ Time Frame: 6 weeks postoperative ]
    Resumed normal daily activities using the Activities Assessment Scale (AAS) by 6 weeks after surgery. The AAS is a 13-point scale on which patients rate their difficulty performing a range of activities from "No difficulty" to "Not able to do it." A final score ranging from 0-100 is transformed, with higher numbers reflecting less difficulty with activities. We defined return to normal as when a patient's postoperative AAS scores was at or greater than the baseline AAS score. We report the proportion of patients in each study arm who returned to baseline activity at each timepoint.
  • Return to Baseline Activities Using the Activities Assessment Scale [ Time Frame: 12 weeks postoperative ]
    Resumed normal daily activities using the Activities Assessment Scale (AAS) by 12 weeks after surgery. The AAS is a 13-point scale on which patients rate their difficulty performing a range of activities from "No difficulty" to "Not able to do it." A final score ranging from 0-100 is transformed, with higher numbers reflecting less difficulty with activities. We defined return to normal as when a patient's postoperative AAS scores was at or greater than the baseline AAS score. We report the proportion of patients in each study arm who returned to baseline activity at each timepoint.
  • POD 1 Narcotic Consumption [ Time Frame: Postoperative day 1 ]
    The total amount of narcotic pain medication used on postoperative day 1 was calculated and measured in oral morphine equivalents.
  • POD 2 Narcotic Consumption [ Time Frame: Postoperative day 2 ]
    The total amount of narcotic pain medication used on postoperative day 2 was calculated and measured in oral morphine equivalents.
  • POD 3 Narcotic Consumption [ Time Frame: Postoperative day 3 ]
    The total amount of narcotic pain medication used on postoperative day 3 was calculated and measured in oral morphine equivalents.
  • POD 1 Ibuprofen Consumption [ Time Frame: Postoperative day 1 ]
    The total amount of ibuprofen medication used on postoperative day 1.
  • POD 2 Ibuprofen Consumption [ Time Frame: Postoperative day 2 ]
    The total amount of ibuprofen medication used on postoperative day 2.
  • POD 3 Ibuprofen Consumption [ Time Frame: Postoperative day 3 ]
    The total amount of ibuprofen medication used on postoperative day 3.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2017)
  • Other Postoperative Pain measured by the NRS [ Time Frame: 3, 48 and 72 hours and 1 week postoperatively ]
    Postoperative pain as measured by the NRS.
  • Length of stay [ Time Frame: 0-24 hours postoperatively ]
    Length of stay in postoperative recovery area and length of hospital stay (both measured in hours)
  • Same Day Discharge Rates [ Time Frame: 0-24 hours postoperatively ]
    Whether a patient was discharged to home on the same day of surgery, recorded as a yes or no.
  • Urinary Retention (Recorded as a Yes or no) [ Time Frame: 0-24 hours postoperatively ]
    Whether a patient needed to perform self-catheterization or have an indwelling catheter placed postoperatively, recorded as a yes or no.
  • Adverse Events [ Time Frame: 0-6 weeks postoperatively ]
    Adverse intraoperative and postoperative events including medical and surgical complications
  • Analgesic Consumption [ Time Frame: 0-72 hours postoperatively ]
    Postoperative consumption of narcotics (measured in morphine equivalents) and non-steroidal anti-inflammatory medications while in the hospital and during the first 3 days after discharge
  • Nausea and Vomiting Measured by the PONV Scale [ Time Frame: 3 hours postoperatively ]
    Intensity of postoperative nausea and vomiting (PONV) measured by the PONV scale prior to discharge
  • Anti-emetic Consumption [ Time Frame: 3 hours postoperatively ]
    The amount of inpatient anti-emetic consumption, recorded in number of doses of nausea medication
  • Activities Assessment using the Activities Assessment Scale [ Time Frame: 1 week, 2 weeks, 6 weeks and 12 weeks postoperatively ]
    Time to resume normal daily activities using the Activities Assessment Scale (AAS).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block for Pain Control After Vaginal Reconstructive Surgery
Official Title  ICMJE Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block With Bupivacaine and Dexamethasone for Improved Pain Control After Vaginal Reconstructive Surgery: A Three-Arm Randomized Controlled Trial
Brief Summary

To test the hypothesis that preoperative injections along the levator ani muscles and pudendal nerve with bupivacaine and dexamethasone improve pain control after vaginal apical reconstructive surgery. A three-arm, double-blinded, randomized controlled trial of a total of 75 women will be performed.

The study population will be adult women (>18 years of age) with uterovaginal or vaginal vault prolapse who have been scheduled for native tissue vaginal reconstructive surgery which includes an apical support procedure. Participants will be enrolled prior to surgery. The procedure will involved four injection sites: the bilateral levator ani muscles via a transobturator approach and bilateral pudendal nerves via a transvaginal approach. Random assignment will occur to one of three study arms: combined arm (20 milliliters bupivacaine/dexamethasone solution divided between the 4 injection sites), bupivacaine arm (20 milliliters bupivacaine divided between the 4 injection sites), or placebo arm (20 milliliters saline divided between the 4 injection sites).

Detailed Description

The primary purpose of this three arm, randomized clinical trial is to test the hypothesis that preoperative injections along the levator ani muscles and pudendal nerve with bupivacaine and dexamethasone improve pain control after vaginal native tissue apical reconstructive surgery.

Hypothesis: concurrent bilateral transobturator levator ani muscle injections and transvaginal pudendal nerve blocks with bupivacaine and dexamethasone performed prior to vaginal apical support procedures will result in improved pain scores at 24 hours postoperatively.

Participants will be randomized to three arms: bupivacaine/dexamethasone group, bupivacaine group, and placebo group. Block randomization will occur and will be stratified by surgery type to ensure that similar numbers of each procedure are randomized to each study arm.

All 3 groups will receive pudendal nerve blocks and transobturator levator ani muscle injections as outlined in detail below (with either bupivacaine/dexamethasone, bupivacaine alone or saline depending on randomization). The interventions will be performed after the participant is positioned in lithotomy position and after sterile preparation of the vagina and perineum per standard protocol. These injections will be performed at the start of the procedure prior to any vaginal repair and be administered by either the attending surgeon or the urogynecology fellow. After the interventions below, the vaginal reconstructive procedures will be performed as usual by the attending surgeon and surgical team. There are both fellows and residents who participate in these vaginal reconstructive surgeries, however for study purposes, resident physicians will not be permitted to administer either the pudendal nerve block or the transobturator injections. There are four attending surgeons and four fellow physicians who will be administering the injections. While all surgeons are familiar with the anatomy and have performed these procedures, each physician will be instructed on the intended procedures and additionally will be directly observed in the operating room for at least one procedure to ensure consistency in technique. All participants will undergo a standardized general anesthesia regimen.

After the study intervention, all participants will then undergo the scheduled vaginal reconstructive procedure as standard. Infiltration of the vaginal epithelium with lidocaine is common in vaginal repairs. The maximum doses of lidocaine and bupivacaine are additive. The amount of local infiltration to 50 milliliters of 0.5% lidocaine with epinephrine. This dose is equal to 250mg of lidocaine which, when also taking into account the 50mg of bupivacaine, is within a safe dosing range for a participant weighing 50kg.

Administration of all four injections involved in the study protocol and described above take approximately 5 additional minutes in total at the start of the case. After the injections are performed, there will be no further interventions.

Other assessments that will be performed as part of the study protocol are outlined below:

Baseline assessments: Pain assessment, assessment of presence of any baseline nausea or vomiting, baseline activities assessment will all be performed in preoperative area on the day of surgery prior to randomization.

Postoperative pain score assessment: 3 hours, 24 hours, 48 hours, 72 hours, and 1 week postoperatively. Postoperative pain measured by the numerical rating scale (NRS). The NRS is a publicly available pain assessment tool that consists of an eleven point scale ranging from 0 to 10 (0 = no pain and 10 = worst possible pain) presented visually on a horizontal line. Participants are asked to report a number or mark on the scale. Previous studies have demonstrated its reliability, validity and ease of administration. The NRS was chosen because a systematic review article demonstrated higher compliance rates, better responsiveness and ease of use relative to visual analog scales. Additionally, the NRS has been shown to have strong validity and low error rates when used in an elderly (>60 years) postoperative patient population.

Postoperative nausea and vomiting assessment: 3 hours postoperatively The intensity of postoperative nausea and vomiting (PONV) using the PONV Intensity scale. The PONV scale is a four question assessment designed to measure clinically significant nausea and vomiting. It was initially validated in a general surgery population and has been validated in early postoperative gynecology patients. Clinically important nausea and vomiting is defined as a score greater than or equal to 50. This scale takes approximately 1 minute to complete and is publicly available. The amount of inpatient anti-emetic consumption will also be assessed. Any anti-emetic administered from surgery end time will be recorded as well as the dosage. Anti-emetic type and dosage will be recorded until the time of discharge.

Voiding status at time of foley catheter removal. All patients routinely have some assessment of voiding function prior to discharge. Whether each participant passed or failed a voiding trial after surgery will be recorded in the database. If a participant fails, the standard of care is do be discharged to home after learning self-catheterization or with a foley catheter. In the event that a participant fails a postoperative voiding trial, whether participants receive a foley catheter or were performing self-catheterization will be recorded. As this is a routine part of postoperative care, the research protocol will not interfere with the performance or outcomes of a voiding trial. Results will be documented, however no specific assessment tool will be used.

Time to resume normal activities measured by the activities assessment scale (AAS): 1 week, 2 weeks, 6 weeks and 12 weeks postoperatively The AAS was initially designed to assess functional activity in the perioperative period in the general surgery population. It has since been deemed a valid and reliable measure to assess postoperative activity level in a Female Pelvic Medicine and Reconstructive Surgery patient population. It has the ability to measure perioperative function and takes approximately 3-5 minutes to complete. It consists of a 13 item questionnaire assessing various types of physical activity and the degree of difficulty associated with each activity. The types of activities assessed fall into three subscales: sedentary activities (questions 1-4), ambulatory activities (questions 6-8), and work or exercise activities (questions 11-13). Respondents also have the option to indicate that these activities were not performed for another indication (this item is not scored). The time frame for all questions is the previous 24 hours. Given that many patients are instructed to avoid strenuous work or exercise activity in the postoperative period, the subscales of sedentary activities and ambulatory activities, which patients are encouraged to perform as tolerated in the postoperative period, will be of most interest.

Consumption of analgesic medications: during inpatient hospital stay and for first 72 hours postoperatively Narcotic consumption will be measured in morphine equivalents. The amount of narcotics will be obtained from the inpatient hospital record. All narcotics received from the surgery end time to the time of discharge will be included. Morphine equivalents will be calculated with online calculator available at http://www.agencymeddirectors.wa.gov/Calculator/DoseCalculator.htm. Similarly, the amount of NSAIDs will be obtained from the inpatient hospital record. All NSAIDs received from the surgery end time to the time of discharge will be included. To assess both the amount of narcotic and NSAID consumption after discharge, the participant will be provided with a diary form to record how many daily tablets of narcotic and NSAIDs are taken. This form will be completed from postoperative days 1-3.

For all forms, the participants will be instructed to mail the forms back to the office once completed (in a pre-address envelope provided as part of the study). Participants will also have the option of brining the forms in to the office at the time of a participant's postoperative visit.

Participants, physicians and any nursing personnel involved in patient care will remain masked until 12 weeks postoperatively.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Three-arm, double-blinded, placebo-controlled, randomized controlled trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blinded
Primary Purpose: Treatment
Condition  ICMJE
  • Pelvic Organ Prolapse
  • Surgery
  • Postoperative Pain
Intervention  ICMJE
  • Drug: Dexamethasone
    Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
    Other Name: Decadron
  • Drug: Bupivacaine
    Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
    Other Name: Marcaine
  • Procedure: Bilateral Pudendal Nerve Block
    Performed transvaginally. The ischial spines will be palpated transvaginally and the sacrospinous ligament identified as a firm band running medially and posteriorly from the ischial spine to the sacrum. The needle guide will be inserted and positioned against the vaginal mucosa on the sacrospinous ligament approximately 1 cm medial and inferior to the ischial spine. When the needle guide is properly positioned, the spinal needle is advanced approximately 1cm through the vaginal mucosa into the sacrospinous ligament. The needle will be aspirated to ensure no intravascular needle placement. With a negative aspirate, 5 milliliters of solution are injected. This same procedure will be performed on the contralateral side.
  • Procedure: Bilateral Levator Ani Muscle Injection
    Performed transperineally. With thumb, superomedial aspect of obturator foramen is palpated 2-3 cm lateral to the clitoris. The index and middle finger are in the vagina to confirm obturator foramen. A spinal needle is inserted through the the obturator foramen into the obturator internus muscle. The needle is angled slightly posteriorly towards the ischial spine, parallel to the arcus tendineus levator ani and arcus tendineus fascia pelvis. The needle is advanced to the level of the ischial spine, the vaginal hand ensuring that the needle has not perforated the vaginal wall. Once the needle tip is at a depth of the ischial spine, aspiration is performed to ensure no intravascular needle placement. 5 milliliters of solution is injected along the length of the needle tract.
  • Drug: Saline
    Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
    Other Name: Normal Saline
Study Arms  ICMJE
  • Experimental: Bupivacaine/Dexamethasone Arm
    After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of a mixture of 20 milliliters of 0.25% bupivacaine (2.5mg/milliliter ) and 2 milliliters of dexamethasone (4mg/milliliter). The total amount of the bupivacaine/dexamethasone solution will be divided equally between the four injection sites.
    Interventions:
    • Drug: Dexamethasone
    • Drug: Bupivacaine
    • Procedure: Bilateral Pudendal Nerve Block
    • Procedure: Bilateral Levator Ani Muscle Injection
  • Active Comparator: Bupivacaine Arm
    After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.25% bupivacaine (2.5mg/milliliter). The total amount will be divided equally between the four injection sites.
    Interventions:
    • Drug: Bupivacaine
    • Procedure: Bilateral Pudendal Nerve Block
    • Procedure: Bilateral Levator Ani Muscle Injection
  • Placebo Comparator: Placebo Arm
    After sterile preparation in lithotomy position, investigators will perform bilateral levator ani muscle injection via the obturator foramen (transobturator). After transobturator injections are performed on each side, bilateral pudendal nerve blocks will be performed transvaginally as described in the literature. The solution injected at all 4 of the above injections sites will consist of 20 milliliters 0.9% saline (normal saline). The total amount will be divided equally between the four injection sites.
    Interventions:
    • Procedure: Bilateral Pudendal Nerve Block
    • Procedure: Bilateral Levator Ani Muscle Injection
    • Drug: Saline
Publications *

*   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: February 7, 2020)
79
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2017)
75
Actual Study Completion Date  ICMJE August 5, 2019
Actual Primary Completion Date April 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Women ages 18 or older who are scheduled for a vaginal native tissue repair with apical support procedure including uterosacral ligament suspension, sacrospinous ligament fixation, or colpectomy and colpocleisis with or without levator myorrhaphy
  2. Concomitant procedures including hysterectomy, anterior and posterior colporrhaphies , perineorrhaphies and midurethral sling placements are acceptable and do not result in exclusion
  3. Available for at least 12 weeks of follow-up
  4. Able to undergoing general anesthesia

Exclusion Criteria:

  1. Planned mesh-augmented apical support procedure (placement of synthetic midurethral sling is acceptable and not considered an exclusion criteria)
  2. Planned mesh excision
  3. Laparoscopic, robotic or abdominal surgery
  4. Known adverse reaction or allergy to intervention medication
  5. Evidence of fistula or known infection (vulvovaginal cellulitis, abscess, abdominopelvic infection, or systemic fungal infection)
  6. Chronic pelvic pain as an active issue
  7. Daily opiate consumption for any indication
  8. History of pelvic radiation
  9. Chronic steroid use
  10. Diabetes mellitus
  11. Known HIV/AIDS or immunosuppression secondary to transplant related medications
  12. Planned surgery under regional anesthesia
  13. Non-English speaking or inability to complete questionnaires
  14. Bleeding disorders that would impair a patient's clotting ability
  15. Weight less than 50kg
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
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 NCT03040011
Other Study ID Numbers  ICMJE PRO16110378
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: No
Responsible Party Lauren Giugale, MD, University of Pittsburgh
Study Sponsor  ICMJE Lauren Giugale, MD
Collaborators  ICMJE Magee-Womens Research Institute
Investigators  ICMJE
Principal Investigator: Lauren Giugale, MD University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date March 2020

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