Pelvic Organ ProlapsePhase 1/2NCT03040011
Preoperative Levator Ani Muscle Injection and Pudendal Nerve Block for Pain Control After Vaginal Reconstructive Surgery
A Phase 1/2 study testing Dexamethasone, Bupivacaine and Bilateral Pudendal Nerve Block in people with Pelvic Organ Prolapse and Surgery, run by Lauren Giugale, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pelvic Organ Prolapse, Surgery, Postoperative Pain
- What is being tested?
- Dexamethasone, Bupivacaine and Bilateral Pudendal Nerve Block
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 5 Aug 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
- Concomitant procedures including hysterectomy, anterior and posterior colporrhaphies , perineorrhaphies and midurethral sling placements are acceptable and do not result in exclusion
- Available for at least 12 weeks of follow-up
- Able to undergoing general anesthesia
Who cannot join
- Planned mesh-augmented apical support procedure (placement of synthetic midurethral sling is acceptable and not considered an exclusion criteria)
- Planned mesh excision
- Laparoscopic, robotic or abdominal surgery
- Known adverse reaction or allergy to intervention medication
- Evidence of fistula or known infection (vulvovaginal cellulitis, abscess, abdominopelvic infection, or systemic fungal infection)
- Chronic pelvic pain as an active issue
Show all 15Show fewer
- Daily opiate consumption for any indication
- History of pelvic radiation
- Chronic steroid use
- Diabetes mellitus
- Known HIV/AIDS or immunosuppression secondary to transplant related medications
- Planned surgery under regional anesthesia
- Non-English speaking or inability to complete questionnaires
- Bleeding disorders that would impair a patient's clotting ability
- Weight less than 50kg
Trial locations and contacts
1 site in 1 country.
United States1 site
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, 15213
About this study
Official title: 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
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).
Read the 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.
- Conditions
- Pelvic Organ Prolapse, Surgery, Postoperative Pain
- Being tested
- Dexamethasone, Bupivacaine, Bilateral Pudendal Nerve Block, Bilateral Levator Ani Muscle Injection, Saline
- Keywords
- Vaginal Surgery, Pelvic Organ Prolapse, Postoperative Pain
- Medical subject headings
- Pelvic Organ Prolapse, Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called Decadron
Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
BupivacaineDrug
Also called Marcaine
Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
Bilateral Pudendal Nerve BlockProcedure or surgery
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.
Bilateral Levator Ani Muscle InjectionProcedure or surgery
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.
SalineDrug
Also called Normal Saline
Pudendal Nerve and Levator Muscle Injection. See additional information in study arm description.
| Study group | Role | What they receive |
|---|---|---|
| Bupivacaine/Dexamethasone Arm | Experimental | 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. Receives: Drug: Dexamethasone; Drug: Bupivacaine; Procedure: Bilateral Pudendal Nerve Block; Procedure: Bilateral Levator Ani Muscle Injection |
| Bupivacaine Arm | Active comparator | 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. Receives: Drug: Bupivacaine; Procedure: Bilateral Pudendal Nerve Block; Procedure: Bilateral Levator Ani Muscle Injection |
| Placebo Arm | Placebo comparator | 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. Receives: Procedure: Bilateral Pudendal Nerve Block; Procedure: Bilateral Levator Ani Muscle Injection; Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Postoperative Pain Measured by the Numerical Rating Scale (NRS)
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.
Measured: 24 hours postoperatively
Secondary outcomes (19)
6 Hour Postoperative Pain Measured by the NRS
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.
Measured: 6 hours postoperatively
POD 2 Postoperative Pain Measured by the NRS
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.
Measured: 2 days after surgery
POD 3 Postoperative Pain Measured by the NRS
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.
Measured: 3 days after surgery
1 Week Postoperative Pain Measured by the NRS
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.
Measured: 1 week after surgery
Proportion of Patients With Same Day Discharge
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.
Measured: Day of surgery
Postoperative Urinary Retention
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.
Measured: 0-24 hours postoperatively
Adverse Events
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.
Measured: 0-12 weeks postoperatively
Nausea and Vomiting Measured by the PONV Scale
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.
Measured: 6 hours postoperatively
Anti-emetic Consumption
The amount of inpatient anti-emetic consumption, recorded in number of doses of nausea medication
Measured: 3 hours postoperatively
Return to Baseline Activities Using the Activities Assessment Scale
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.
Measured: 1 week postoperative
Return to Baseline Activities Using the Activities Assessment Scale
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.
Measured: 2 week postoperative
Return to Baseline Activities Using the Activities Assessment Scale
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.
Measured: 6 weeks postoperative
Return to Baseline Activities Using the Activities Assessment Scale
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.
Measured: 12 weeks postoperative
POD 1 Narcotic Consumption
The total amount of narcotic pain medication used on postoperative day 1 was calculated and measured in oral morphine equivalents.
Measured: Postoperative day 1
POD 2 Narcotic Consumption
The total amount of narcotic pain medication used on postoperative day 2 was calculated and measured in oral morphine equivalents.
Measured: Postoperative day 2
POD 3 Narcotic Consumption
The total amount of narcotic pain medication used on postoperative day 3 was calculated and measured in oral morphine equivalents.
Measured: Postoperative day 3
POD 1 Ibuprofen Consumption
The total amount of ibuprofen medication used on postoperative day 1.
Measured: Postoperative day 1
POD 2 Ibuprofen Consumption
The total amount of ibuprofen medication used on postoperative day 2.
Measured: Postoperative day 2
POD 3 Ibuprofen Consumption
The total amount of ibuprofen medication used on postoperative day 3.
Measured: Postoperative day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2017 (estimated)
- Study start1 Jun 2017
- Primary completion11 Apr 2019
- Study completion5 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pelvic Organ ProlapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Three-arm, double-blinded, placebo-controlled, randomized controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lauren Giugale, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Magee-Women's Research Institute
- Responsible party
- Sponsor-investigator, Lauren Giugale, MD, University of Pittsburgh
- Investigators
- Lauren Giugale, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03040011
- Sponsor's protocol ID
- PRO16110378
- Status last verified
- Mar 2020
- First submitted
- 25 Jan 2017
- Last updated
- 9 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Dexamethasone (systemic): Drug information. UpToDate; 2016. Accessed November 9, 2016.
Bupivacaine: Drug Information. UpToDate; 2016.
Hsu D. Infiltration of local anesthetics. UpToDate. 2016. Accessed November 30, 2016.
Giugale LE, Baranski LA, Meyn LA, Schott NJ, Emerick TD, Moalli PA. Preoperative Pelvic Floor Injections With Bupivacaine and Dexamethasone for Pain Control After Vaginal Prolapse Repair: A Randomized Controlled Trial. Obstet Gynecol. 2021 Jan 1;137(1):21-31. doi: 10.1097/AOG.0000000000004205.
PubMed 33278291
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03040011
- Acronym / sponsor ID
- PRO16110378
- Conditions
- Pelvic Organ Prolapse, Surgery, Postoperative Pain
- Keywords
- Vaginal Surgery, Pelvic Organ Prolapse, Postoperative Pain
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- Lauren Giugale, MDUniversity, hospital or other
- Collaborators
- Magee-Women's Research Institute
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 11 Apr 2019 (actual)
- Study completion
- 5 Aug 2019 (actual)
- First posted
- 1 Feb 2017 (estimated)
- Results
- Posted 9 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Three-arm, double-blinded, placebo-controlled, randomized controlled trial
| Arm | Type | Receives |
|---|---|---|
| Bupivacaine/Dexamethasone Arm | Experimental | Drug: Dexamethasone, Drug: Bupivacaine, Procedure: Bilateral Pudendal Nerve Block, Procedure: Bilateral Levator Ani Muscle InjectionAfter 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. |
| Bupivacaine Arm | Active comparator | Drug: Bupivacaine, Procedure: Bilateral Pudendal Nerve Block, Procedure: Bilateral Levator Ani Muscle InjectionAfter 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. |
| Placebo Arm | Placebo comparator | Procedure: Bilateral Pudendal Nerve Block, Procedure: Bilateral Levator Ani Muscle Injection, Drug: SalineAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
- Concomitant procedures including hysterectomy, anterior and posterior colporrhaphies , perineorrhaphies and midurethral sling placements are acceptable and do not result in exclusion
- Available for at least 12 weeks of follow-up
- Able to undergoing general anesthesia
Key exclusion criteria (15 listed)
- Planned mesh-augmented apical support procedure (placement of synthetic midurethral sling is acceptable and not considered an exclusion criteria)
- Planned mesh excision
- Laparoscopic, robotic or abdominal surgery
- Known adverse reaction or allergy to intervention medication
- Evidence of fistula or known infection (vulvovaginal cellulitis, abscess, abdominopelvic infection, or systemic fungal infection)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: DecadronPudendal Nerve and Levator Muscle Injection. See additional information in study arm description. | Drug | Bupivacaine/Dexamethasone Arm |
| BupivacaineAlso: MarcainePudendal Nerve and Levator Muscle Injection. See additional information in study arm description. | Drug | Bupivacaine Arm, Bupivacaine/Dexamethasone Arm |
| Bilateral Pudendal Nerve BlockPerformed 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 or surgery | Bupivacaine Arm, Bupivacaine/Dexamethasone Arm, Placebo Arm |
| Bilateral Levator Ani Muscle InjectionPerformed 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. | Procedure or surgery | Bupivacaine Arm, Bupivacaine/Dexamethasone Arm, Placebo Arm |
| SalineAlso: Normal SalinePudendal Nerve and Levator Muscle Injection. See additional information in study arm description. | Drug | Placebo Arm |
Primary outcome
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.
19 secondary outcomes
6 Hour Postoperative Pain Measured by the NRS
Time frame: 6 hours postoperatively
POD 2 Postoperative Pain Measured by the NRS
Time frame: 2 days after surgery
POD 3 Postoperative Pain Measured by the NRS
Time frame: 3 days after surgery
1 Week Postoperative Pain Measured by the NRS
Time frame: 1 week after surgery
Proportion of Patients With Same Day Discharge
Time frame: Day of surgery
Postoperative Urinary Retention
Time frame: 0-24 hours postoperatively
Adverse Events
Time frame: 0-12 weeks postoperatively
Nausea and Vomiting Measured by the PONV Scale
Time frame: 6 hours postoperatively
Anti-emetic Consumption
Time frame: 3 hours postoperatively
Return to Baseline Activities Using the Activities Assessment Scale
Time frame: 1 week postoperative
Return to Baseline Activities Using the Activities Assessment Scale
Time frame: 2 week postoperative
Return to Baseline Activities Using the Activities Assessment Scale
Time frame: 6 weeks postoperative
Return to Baseline Activities Using the Activities Assessment Scale
Time frame: 12 weeks postoperative
POD 1 Narcotic Consumption
Time frame: Postoperative day 1
POD 2 Narcotic Consumption
Time frame: Postoperative day 2
POD 3 Narcotic Consumption
Time frame: Postoperative day 3
POD 1 Ibuprofen Consumption
Time frame: Postoperative day 1
POD 2 Ibuprofen Consumption
Time frame: Postoperative day 2
POD 3 Ibuprofen Consumption
Time frame: Postoperative day 3
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundDexamethasone (systemic): Drug information. UpToDate; 2016. Accessed November 9, 2016.
- BackgroundBupivacaine: Drug Information. UpToDate; 2016.
- BackgroundHsu D. Infiltration of local anesthetics. UpToDate. 2016. Accessed November 30, 2016.
- Derived from this study: PubMed 33278291Giugale LE, Baranski LA, Meyn LA, Schott NJ, Emerick TD, Moalli PA. Preoperative Pelvic Floor Injections With Bupivacaine and Dexamethasone for Pain Control After Vaginal Prolapse Repair: A Randomized Controlled Trial. Obstet Gynecol. 2021 Jan 1;137(1):21-31. doi: 10.1097/AOG.0000000000004205.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lauren Giugale, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dexamethasone, Bupivacaine and Bilateral Pudendal Nerve Block in people with Pelvic Organ Prolapse and Surgery, run by Lauren Giugale, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Postoperative Pain Measured by the Numerical Rating Scale (NRS) (time frame: 24 hours postoperatively). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03040011, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2020.