Local Anesthesia for Vaginal Lacerations

(PAIN Trial)

Overseen By Fatima Estrada, MD, FACOG

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Montefiore Medical Center

Must be taking: Epidural analgesia

Disqualifiers: Operative delivery, Multiple gestation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Immediate

100 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications, so it's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Bupivacaine with Epinephrine for treating vaginal lacerations?

Research shows that bupivacaine with epinephrine is effective in providing local anesthesia during laceration repairs, as it has a longer duration of action and a favorable balance between potency and safety compared to other anesthetics. ^{1 2 3 4 5}

Is Bupivacaine with Epinephrine safe for use in humans?

Bupivacaine with Epinephrine is generally considered safe for use in humans, with studies showing minimal side effects when used in obstetrics and facial plastic surgery, provided that recommended doses are followed. ^{1 6 7 8 9}

What makes the drug Bupivacaine with Epinephrine unique for treating vaginal lacerations?

Bupivacaine with Epinephrine is unique because it combines a long-lasting local anesthetic (Bupivacaine) with a vasoconstrictor (Epinephrine) that helps reduce bleeding and prolongs the anesthetic effect, which may be particularly beneficial for managing pain and bleeding during vaginal laceration repair. ^{3 5 8 10 11}

What is the purpose of this trial?

The prevalence of perineal lacerations is more than 75% of all vaginal deliveries. The repair of such lacerations in the institution is usually done using lidocaine for non-epiduralized patients versus no local injection in patients with a pre-existing epidural analgesia. The prevalence of epidural analgesia use among women who underwent vaginal delivery in cross-sectional study of over 2 million deliveries in the United States was 71.1%. Once the analgesic effect of the epidural analgesia fades, the laceration may cause uncontrolled postpartum pain which can affect both the physical and mental recovery period, extend hospital stays, and increase the potential for serious adverse reactions with pain medications. The research hypothesis of this study is that adding a locally injected analgesic, which will take effect once the epidural analgesia fades, may alleviate perineal pain and improve women's overall well-being and satisfaction. This is a superiority two-arm, quadruple-blinded, prospective randomized controlled trial with the objective to determine if prolonged analgesia and higher rate of maternal satisfaction are found when bupivacaine with epinephrine infiltration is used for perineal repair as compared to sham injection in patients with pre-existing effective epidural analgesia at time of perineal laceration repair. Women with a working epidural analgesia, and status post a vaginal delivery involving a second-degree laceration will be invited to participate. Women in the local anesthesia (LA) arm will get a LA injected to the laceration and women in the sham arm will get an injection with saline. The differences in perineal pain between the groups will be evaluated at time of the first analgesic (TFA) demand, maternal satisfaction at 24 hours, and visual analog scale (VAS) pain score.

Research Team

Fatima Estrada, MD, FACOG

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for healthy women over 18 who've had a single baby delivered vaginally, resulting in a second-degree perineal tear. They must speak English or Spanish and be able to consent for themselves. It's not specified who can't join.

Inclusion Criteria

My epidural is working during my laceration repair.

Healthy with a singleton pregnancy

I can make my own medical decisions.

Exclusion Criteria

Allergic to bupivacaine and/or epinephrine

I received a combined spinal-epidural anesthesia.

Multiple gestation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive either bupivacaine with epinephrine or a saline sham injection for perineal laceration repair

Immediate

1 visit (in-person)

Immediate Follow-up

Participants' pain levels and time to first analgesic demand are assessed immediately and up to 24 hours after treatment

24 hours

Continuous monitoring

Follow-up

Maternal satisfaction and pain levels are assessed 48 hours after treatment

48 hours

1 visit (in-person or virtual)

Treatment Details

Interventions

• Bupivacaine with Epinephrine

Trial Overview The study tests if injecting bupivacaine with epinephrine reduces pain better than a fake (saline) injection after epidural anesthesia wears off post-vaginal delivery. Women are randomly assigned to either the real drug or sham treatment without knowing which one they receive.

Participant Groups

Group I: Local Anesthesia arm Experimental Treatment 2 Interventions

Bupivicaine and Epinephrine

Group II: Normal saline sham arm Placebo Group 1 Intervention

Bupivacaine with Epinephrine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Bupivacaine with Epinephrine for:

• Local anesthesia for surgical procedures
• Pain relief for dental procedures
• Regional anesthesia for childbirth

Approved in European Union as Bupivacaine with Epinephrine for:

• Local anesthesia for surgical procedures
• Pain relief for dental procedures
• Regional anesthesia for childbirth
• Postoperative pain management

Approved in Canada as Bupivacaine with Epinephrine for:

• Local anesthesia for surgical procedures
• Pain relief for dental procedures
• Regional anesthesia for childbirth

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Findings from Research

Bupivacaine hydrochloride (Marcaine) is highlighted for its increased duration of action compared to other local anesthetics, making it particularly useful in oral surgery.

It also has a favorable potency to toxicity ratio, suggesting that it provides effective pain relief with a lower risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review. Babst, CR., Gilling, BN.[2018]

In a study involving 180 children with lacerations requiring suturing, the new topical anesthetic prilocaine-phenylephrine was found to be effective and safer than the traditional TAC (tetracaine-adrenaline-cocaine) anesthetic, with no significant pain difference reported by patients.

While both prilocaine-phenylephrine and bupivacaine-phenylephrine were effective, prilocaine-phenylephrine statistically outperformed bupivacaine-phenylephrine, making it a promising alternative for laceration repair in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations. Smith, GA., Strausbaugh, SD., Harbeck-Weber, C., et al.[2019]

In a study involving 71 children with facial or scalp lacerations, the new topical anesthetic Mepivanor was found to be less effective than both TAC and 1% lidocaine infiltration for providing adequate anesthesia during laceration repair.

TAC, which contains a small amount of cocaine, was as effective as 1% lidocaine infiltration, suggesting that TAC can be used with reduced cocaine content, potentially lowering costs and minimizing the risk of adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of topical anesthetics with lidocaine infiltration during laceration repair in children. Smith, GA., Strausbaugh, SD., Harbeck-Weber, C., et al.[2017]

In a study of 52 adult patients with simple lacerations, benzyl alcohol (BA) was found to cause significantly less pain during infiltration compared to lidocaine (LID), with median pain scores of 7.5 mm for BA versus 19.5 mm for LID (p = 0.049).

Although more patients in the BA group required additional anesthesia (8 out of 26) compared to the LID group (2 out of 26), this difference was not statistically significant, suggesting that BA can be a suitable alternative for patients allergic to LID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benzyl alcohol with epinephrine as an alternative to lidocaine with epinephrine. Bartfield, JM., May-Wheeling, HE., Raccio-Robak, N., et al.[2019]

In a study involving 90 children with mucous membrane lacerations, the traditional lidocaine infiltration was found to be significantly more effective than the new topical anesthetic TetraLidoPhen in reducing pain during suturing, as measured by various pain scales.

Despite TetraLidoPhen being statistically inferior to lidocaine, it was deemed safe for use on mucous membranes, with a low wound complication rate of 4.4%, suggesting that further research is needed to fully assess its clinical utility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tetracaine-lidocaine-phenylephrine topical anesthesia compared with lidocaine infiltration during repair of mucous membrane lacerations in children. Smith, GA., Strausbaugh, SD., Harbeck-Weber, C., et al.[2017]

In a randomized, double-blind study comparing 1% lidocaine with epinephrine to 0.5% bupivacaine with epinephrine for facial plastic surgery, bupivacaine demonstrated effective and safe anesthesia.

Bupivacaine, being a longer-acting local anesthetic, may provide better surgical conditions compared to lidocaine, making it a suitable choice for facial procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine v bupivacaine in facial plastic surgery. A clinical trial. Maimon, WN., Schuller, DE.[2022]

Bupivacaine (Marcaine) is effective for epidural analgesia in obstetrics, providing excellent sensory block with minimal impact on motor function and few side effects for both mothers and newborns.

When used at concentrations below 0.5%, and with careful dosing during labor, the risk of side effects and toxicity is low, and significant effects on newborns are rare due to the drug's high protein binding limiting its transfer across the placenta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. Seebacher, J., Chareire, F., Galli-Douant, P., et al.[2013]

Buffered lidocaine with epinephrine and plain lidocaine with epinephrine were found to be more effective anesthetics for suturing minor lacerations compared to buffered lidocaine alone and diphenhydramine with epinephrine, based on evaluations from both patients and physicians.

Diphenhydramine with epinephrine was significantly more painful to inject than buffered lidocaine or buffered lidocaine with epinephrine, indicating it may not be the best choice for pain management in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison trial of four injectable anesthetics for laceration repair. Ernst, AA., Marvez-Valls, E., Nick, TG., et al.[2019]

In a study involving 30 patients, two forms of 0.5% bupivacaine hydrochloride (Anecaine and Marcaine) were compared for epidural anesthesia, revealing differences in how quickly and effectively they provided pain relief.

Anecaine showed a shorter onset of analgesia at the catheter site but a delayed effect in peripheral areas compared to Marcaine, indicating that even the same active ingredient can behave differently based on the manufacturer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. Kozlov, SP., Vashchinskaia, TV., Svetlov, VA.[2013]

In a study of 183 adult patients with simple lacerations, 1% lidocaine provided significantly lower pain ratings during suturing compared to 2% prilocaine and buffered 1% lidocaine, indicating it may be the most effective local anesthetic for this procedure.

While all three anesthetics showed similar pain levels during the initial injection, 1% lidocaine resulted in the least pain during the actual suturing process, suggesting it may enhance patient comfort during laceration repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prilocaine versus plain or buffered lidocaine for local anesthesia in laceration repair: randomized double-blind comparison. Karcioglu, O., Topacoglu, H., Ayrik, C., et al.[2013]

In a study involving 48 pediatric patients aged 7 to 17 with simple lacerations, applying a topical anesthetic gel (LET) three times at 10-minute intervals did not result in lower pain scores during suturing compared to a single application for 30 minutes.

Both treatment methods showed similar efficacy, with no significant difference in the need for additional anesthesia, indicating that the triple application does not provide a clear advantage over the single application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple Versus Single Application of Lidocaine, Epinephrine, and Tetracaine for Laceration Repair in Children. Siembieda, J., Heyming, T., Padlipsky, P., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Bupivacaine: a review. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Prilocaine-phenylephrine and bupivacaine-phenylephrine topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Comparison of topical anesthetics with lidocaine infiltration during laceration repair in children. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Benzyl alcohol with epinephrine as an alternative to lidocaine with epinephrine. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Tetracaine-lidocaine-phenylephrine topical anesthesia compared with lidocaine infiltration during repair of mucous membrane lacerations in children. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Lidocaine v bupivacaine in facial plastic surgery. A clinical trial. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[The use of Marcaine in obstetrical analgesia]. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

Comparison trial of four injectable anesthetics for laceration repair. [2019]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[A clinical trial of the use of 2 forms of bupivacaine hydrochloride (Anecaine and Marcaine) for epidural anesthesia]. [2013]

10. Croatia pubmed.ncbi.nlm.nih.gov

Prilocaine versus plain or buffered lidocaine for local anesthesia in laceration repair: randomized double-blind comparison. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Triple Versus Single Application of Lidocaine, Epinephrine, and Tetracaine for Laceration Repair in Children. [2023]