ABC for D&E: Addition of Buprenorphine to Paracervical Block for Pain Control During Osmotic Dilator Insertion

Sponsor

University of California, San Diego (Other)

Overall Status

Unknown status

CT.gov ID

NCT04254081

Collaborator

Society of Family Planning (Other)

114

Enrollment

Location

Arms

12.1

Anticipated Duration (Months)

9.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cervical preparation with osmotic dilators is commonly used prior to dilation and evacuation (D&E) procedures to decrease the risk of complications. Women have described the pain of osmotic dilator insertion as moderate to severe yet there have been few studies aimed at addressing pain during and after osmotic dilator insertion. In addition to the discomfort during insertion, pain after osmotic dilator insertion peaks at 2 hours post-insertion with use of a lidocaine paracervical block. One randomized trial found that use of a paracervical block with 1% buffered lidocaine decreased pain with osmotic dilator insertion compared to a sham block. There are adjunct treatments to optimize analgesia with local anesthetics at a variety of anatomic locations. Buprenorphine, a partial mu-opioid receptor agonist, has been found to increase the quality of the anesthetic at the time of administration and increase the duration of nerve block analgesia at several anatomic sites, though has never been studied as an adjunct in a paracervical block. This has been used extensively in orthopedic surgery with significant prolongation of the local anesthetic effect by almost threefold in some studies.

Primary Aim: To compare the mean pain score at the time of osmotic dilator insertion among women randomized to a 1% lidocaine and buprenorphine paracervical block compared to a 1% lidocaine paracervical block alone.

Secondary Aim: To compare the mean pain score 2 hours after osmotic dilator insertion among women randomized to a lidocaine and buprenorphine paracervical block compared to a lidocaine paracervical block alone.

The investigators hypothesize that in patients undergoing osmotic dilator insertion in preparation for dilation and evacuation, the addition of buprenorphine 0.15mg to a 1% lidocaine paracervical block will be associated with lower mean pain scores at time of osmotic dilator insertion compared to women who receive a 1% lidocaine paracervical block alone.

Condition or Disease	Intervention/Treatment	Phase
Procedural Pain Buprenorphine Adjuvants, Anesthesia Dilation and Evacuation Analgesics	Drug: Buprenorphine 0.15 MG Drug: Lidocaine 1% Injectable Solution	Phase 4

Detailed Description

Dilation and evacuation (D&E) is the most common method of second trimester abortion in the United States. Cervical preparation prior to the procedure is essential in order to allow passage of operative instruments and pregnancy tissue safely through the cervix and to decrease the risk of complications. In the second trimester, cervical preparation is typically achieved with placement of osmotic dilators prior to the procedure. Women have described the pain of osmotic dilator insertion as moderate to severe yet there have been few studies aimed at addressing pain during osmotic dilator insertion. A lidocaine paracervical block is commonly used for pain control during other gynecologic procedures including procedures involving cervical dilation like dilation and curettage. One randomized controlled trial found that use of a paracervical block with 1% lidocaine decreased pain with osmotic dilator insertion compared to a sham block. Because the dilators slowly expand after insertion, there is continued discomfort for several hours after placement. Research has shown that pain after osmotic dilator insertion peaks at 2 hours post-insertion with use of a lidocaine paracervical block and a local anesthetic is not sufficient to provide lasting pain relief. Systemic medications, such as gabapentin and narcotic analgesics have been studied to treat post-insertional dilator pain, however these treatments have not been shown to be effective.

There are many adjunct treatments to optimize the duration of local analgesia from a peripheral nerve block. Buprenorphine, a partial mu-opioid receptor agonist, is a high potency, lipophilic opioid and has a high binding capacity for the mu-opioid receptor. Because of the high binding capacity, buprenorphine has the longest duration of action of all opioids. When administered perineurally in combination with a local anesthetic, buprenorphine has been found to drastically increase the duration of analgesia at several anatomic sites, including axillary and subclavian brachial plexus blocks and infragluteal sciatic nerve blocks. With the addition of buprenorphine at doses of 0.15 - 0.3mg, there is significant prolongation of the anesthetic sensory blockade up to three times the duration of the local anesthetic alone. The use of perineural buprenorphine is well established for postoperative analgesia. Buprenorphine itself also has local anesthetic properties. Buprenorphine blocks voltage gated sodium channels and inhibits C-fiber action potentials, thereby contributing to an analgesic effect. Buprenorphine not only prolongs the duration of local anesthetic effect but also improves the analgesic properties when administered in a perineural block.

The addition of buprenorphine to a perineural local anesthetic has not been studied in a paracervical block. This study will be the first trial to assess the efficacy of buprenorphine to provide analgesia for a gynecologic procedure. This medication has the additional benefit of providing long lasting pain relief for procedures that cause continued discomfort after the end of the procedure. The investigators hypothesize that the addition of 0.15mg of buprenorphine to a lidocaine paracervical block will improve pain during osmotic dilator insertion and provide continued pain relief several hours after osmotic dilator insertion. If this intervention proves to provide better pain control than a lidocaine paracervical block alone, it would be an intervention for women during a painful clinic procedure.

A total of 114 women undergoing D&E who require cervical preparation with osmotic dilators will be randomized to one of two study groups: (1) paracervical block with 20mL of 1% buffered lidocaine or (2) paracervical block with 20mL of 1% buffered lidocaine plus 0.15mg of buprenorphine. Participants, clinicians performing the procedure, and study personnel administering questionnaires will be blinded to study assignment. Participants will rate their level of pain on an 11-point numeric rating scale (NRS) during the insertion of osmotic dilators and at several time points after insertion. The primary outcome is to compare the median pain score at the time of osmotic dilator insertion in women randomized to a 1% lidocaine and buprenorphine paracervical block compared to a 1% lidocaine paracervical block alone. Secondary outcomes are to compare the median pain score 2 hours after osmotic dilator insertion; to assess overall narcotic and ibuprofen use after osmotic dilator placement and before dilation and evacuation procedure; to assess opioid related side effects; and to determine patient satisfaction with pain control during and after osmotic dilator insertion.

Primary Hypothesis: The addition of buprenorphine 0.15mg to a paracervical block using 1% lidocaine will be associated with a lower median pain score on the NRS at time of osmotic dilator insertion compared to women who receive a lidocaine paracervical block alone.

Secondary Hypothesis: The addition of buprenorphine 0.15mg to a paracervical block using 1% lidocaine will be associated with a lower median pain score on the NRS 2 hours after osmotic dilator insertion compared to women who receive a lidocaine paracervical block alone.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

114 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This is a randomized, placebo controlled trial with stratified block randomization based on vaginal parity (vaginally nulliparous versus vaginally multiparous). Vaginal parity may influence pain during osmotic dilator insertion and thus the participants will be evenly distributed between strata.This is a randomized, placebo controlled trial with stratified block randomization based on vaginal parity (vaginally nulliparous versus vaginally multiparous). Vaginal parity may influence pain during osmotic dilator insertion and thus the participants will be evenly distributed between strata.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

A clinician who will not be administering the paracervical block will open the designated sealed sequentially numbered opaque randomization envelope containing computer generated randomization code and prepare the designated paracervical block into two 10 mL syringes. The syringes used to prepare the medication will be identical between study groups and the solutions will appear visually identical. A different clinician blinded to the treatment group will perform the standardized procedure for osmotic dilator insertion.

Primary Purpose:

Treatment

Official Title:

Addition of Buprenorphine to Paracervical Block Prior to Osmotic Dilator Insertion for Dilation and Evacuation: A Randomized Controlled Trial

Actual Study Start Date :

May 28, 2020

Anticipated Primary Completion Date :

Jun 1, 2021

Anticipated Study Completion Date :

Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Buprenorphine 0.15mg + 1% lidocaine paracervical block Paracervical block with 18mL of 1% lidocaine buffered with 2 mL 8.4% sodium bicarbonate plus 0.15mg of buprenorphine	Drug: Buprenorphine 0.15 MG Buprenorphine 0.15mg solution will be added to a 20mL 1% buffered lidocaine solution (paracervical block) which will be administered in the paracervical space prior to osmotic dilator insertion.
Placebo Comparator: 1% lidocaine paracervical block Paracervical block with 18 mL of 1% lidocaine buffered with 2 mL 8.4% sodium bicarbonate	Drug: Lidocaine 1% Injectable Solution 20mL of 1% buffered lidocaine solution (paracervical block) will be administered in the paracervical space prior to osmotic dilator insertion.

Arm

Intervention/Treatment

Experimental: Buprenorphine 0.15mg + 1% lidocaine paracervical block

Paracervical block with 18mL of 1% lidocaine buffered with 2 mL 8.4% sodium bicarbonate plus 0.15mg of buprenorphine

Drug: Buprenorphine 0.15 MG

Buprenorphine 0.15mg solution will be added to a 20mL 1% buffered lidocaine solution (paracervical block) which will be administered in the paracervical space prior to osmotic dilator insertion.

Placebo Comparator: 1% lidocaine paracervical block

Paracervical block with 18 mL of 1% lidocaine buffered with 2 mL 8.4% sodium bicarbonate

Drug: Lidocaine 1% Injectable Solution

20mL of 1% buffered lidocaine solution (paracervical block) will be administered in the paracervical space prior to osmotic dilator insertion.

Outcome Measures

Primary Outcome Measures

Pain score at the time of osmotic dilator insertion [Assessed immediately after last dilator inserted]
Median pain score on a 0 (no pain) to 10 (worst pain) numeric rating scale at the time of osmotic dilator insertion

Secondary Outcome Measures

Pain score 2 hours after osmotic dilator insertion [2 hours after osmotic dilator insertion]
Median pain score on a 0 (no pain) to 10 (worst pain) numeric rating scale 2 hours after osmotic dilator insertion assessed via text message
Pain score 1 hour after osmotic dilator insertion [1 hour after osmotic dilator insertion]
Median pain score on a 0 (no pain) to 10 (worst pain) numeric rating scale 1 hour after osmotic dilator insertion assessed via text message
Pain score 6 hours after osmotic dilator insertion [6 hours after osmotic dilator insertion]
Median pain score on a 0 (no pain) to 10 (worst pain) numeric rating scale 6 hours after osmotic dilator insertion assessed via text message
Amount of pain medication required after dilator insertion [Collected with each subject contact (1 hour, 2 hours, 6 hours after osmotic dilator insertion and at time of presentation for D&E)]
Assessment of overall pain medication use (narcotic and/or ibuprofen) between both group after osmotic dilator placement and before dilation and evacuation procedure. Subject report of how many tablets of medication they have taken. This will be assessed via text message.
Frequency of opioid related side effects [Collected with each subject contact (immediately after dilator placement, 1 hour, 2 hours, 6 hours after osmotic dilator insertion and at time of presentation for D&E)]
Assessment of side effects: nausea, vomiting, dizziness, headache, sweating, feeling sleepy. This will be assessed immediately after dilator insertion and via text message at specified time points after dilator insertion.
Patient satisfaction: Likert scale [5 minutes after dilator insertion and on the morning of D&E procedure]
To determine patient satisfaction with pain control during and after osmotic dilator insertion. This will be assessed 5 minutes after dilator insertion and on the morning of D&E procedure. Participants will be asked the following questions and rate responses on a Likert scale: How satisfied are you with the amount of pain control that you had during the procedure? Would you recommend the form of pain control you received today to a friend who was going to have this procedure? If you had to have these dilators placed for a procedure in the future, would you choose to have the same pain medication that you received during your procedure?

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Gestational age 14 0/7 weeks to 23 6/7 weeks at time of osmotic dilator insertion
Require cervical preparation with placement of osmotic dilators
At least 18 years of age
Fluent in English or Spanish