Lidocaine for Syphilis

(LIMIT Trial)

Overseen By Joseph Cherabie, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Washington University School of Medicine

Must be taking: Benzathine penicillin G

Disqualifiers: Penicillin allergy, Lidocaine allergy, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

48 Participants Needed

Trial Summary

What is the purpose of this trial?

There is evidence to suggest that lidocaine can help reduce the pain associated with intramuscular injections of benzathine penicillin G (BPG) or Bicillin, used to treat syphilis infections. A study published in the Journal of Family Practice in 2001 compared the pain experienced during bicillin injections with and without the use of lidocaine. The study found that patients who received lidocaine injections before receiving bicillin reported significantly less pain compared to those who received bicillin injections without lidocaine. Per the International Union against Sexually Transmitted Infections (IUSTI) European Guidelines for syphilis management, lidocaine has been used as a diluent for BPG since 1998. In the United States (US), BPG often comes prepackaged and lidocaine is unable to be used as a diluent with the same ease as it is in Europe. In light of this, the investigators propose a randomized controlled trial of benzathine penicillin G with and without lidocaine to quantify any site pain reduction with lidocaine in patients being treated for syphilis. This study is a randomized, double blinded, placebo controlled trial. During this study, patients needing BPG treatment for syphilis will be screened for any penicillin allergies and consented to their participation. Each participant will receive 2 injections of BPG, 1.2 million units each (2x1.2 million units = 2.4 million units, the standard dose for syphilis treatment), as intramuscular injections, one in each gluteal muscle, with one of the injections randomly having 0.5ml of 1% lidocaine added while the other has 0.5 ml normal saline solution. The side of each injection will be randomized by the medical assistant (MA)/nurse filling the vials and the injecting MA will be blinded, as well as the study participant, as to which vial contains lidocaine and which contains normal saline. The participants will then be asked to rate their pain from 0-10 on each site of injection at 10 minutes post injection, then again at 24 hours after injection via email electronic survey (via RedCap). The differences in pain from the two injections will be compared and analyzed to see if lidocaine reduces pain associated with BPG injections compared to the control of normal saline added to BPG.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Lidocaine for treating syphilis?

Lidocaine has shown antibacterial properties against various bacteria, which suggests it might help in treating infections. However, there is no direct evidence from the provided research that supports its effectiveness specifically for syphilis. ^{1 2 3 4 5}

Is lidocaine generally safe for use in humans?

Lidocaine is commonly used as a local anesthetic and is generally considered safe, but it can cause serious side effects if overdosed, especially in children. Rare allergic reactions and central nervous system toxicity have been reported, so it's important to follow dosage instructions carefully. ^{6 7 8 9 10}

How does lidocaine differ from other drugs for syphilis?

Lidocaine is unique in its potential use for syphilis due to its local anesthetic properties and possible antibacterial effects, which are not typical of standard syphilis treatments like antibiotics. While traditionally used to numb tissue, lidocaine has shown some ability to inhibit bacterial growth, suggesting it might offer additional benefits in treating infections. ^{2 11 12 13 14}

Eligibility Criteria

The LIMIT Trial is for adults over 18 with a confirmed syphilis diagnosis who are receiving their first injection if they require multiple weekly injections. It's not suitable for individuals with penicillin allergies.

Inclusion Criteria

I have been diagnosed with syphilis confirmed by tests.

I am starting my first of three weekly injections for syphilis treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive two intramuscular injections of Benzathine Penicillin G, one with lidocaine and one with saline, to assess pain reduction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for pain at 10 minutes and 24 hours post-injection, and for adverse reactions up to 7 days

1 week

Remote monitoring via electronic survey

Treatment Details

Interventions

• Lidocaine

Trial Overview This trial tests whether adding lidocaine to the benzathine penicillin G (BPG) injection reduces pain compared to using normal saline. Participants will receive two BPG injections, one with lidocaine and one with saline, in a randomized, double-blinded manner.

Participant Groups

Group I: Lidocaine + Benzathine Penicillin G Arm Experimental Treatment 1 Intervention

0.5ml 1% lidocaine solution added to prefilled 1.2 million units Benzathine Pencillin G syringe which will be injected once into the gluteal muscle of the study participant, the side (left or right) to be randomly assigned with the control assigned to the other gluteal muscle.

Group II: Normal Saline + Benzthine Penicillin G Arm Placebo Group 1 Intervention

0.5ml normal saline solution added to prefilled 1.2 million units Benzathine Pencillin G syringe which will be injected once into the gluteal muscle of the study participant, the side (left or right) to be randomly assigned with the study arm assigned to the other gluteal muscle.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

Viscous lidocaine can pose a high risk of overdose in pediatric patients due to their altered pharmacokinetics, making doses safe for adults potentially toxic for children.

Benzocaine is recommended as a safer alternative for treating painful mouth lesions in children, as it has a lower incidence of side effects, but if lidocaine must be used, clear and specific dosing instructions should be provided to parents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine overdose: another preventable case? Gonzalez del Rey, J., Wason, S., Druckenbrod, RW.[2019]

Lidocaine hydrochloride is the most commonly used anesthetic in dermatology, and adverse reactions are very rare, primarily consisting of vasovagal responses and local effects like bruising and swelling.

This report highlights an extremely rare case of a true type I hypersensitivity allergy to lidocaine, which is believed to account for only 1% of all adverse reactions to this anesthetic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case reports: type I hypersensitivity to lidocaine. Haugen, RN., Brown, CW.[2013]

The needle-free powder lidocaine delivery system provided significantly better pain relief compared to a sham placebo in pediatric patients undergoing venipuncture, as shown by lower pain scores on the Wong-Baker FACES scale (P = 0.0022).

The treatment was well tolerated with only minor side effects, such as erythema and petechiae, and no serious adverse events were reported, indicating it is a safe option for providing analgesia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial. Schmitz, ML., Zempsky, WT., Meyer, JM.[2018]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Intravenous lidocaine infusion. [2021]

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

Antimicrobial activity of lidocaine against bacteria associated with nosocomial wound infection. [2022]

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

Safety of Prefilled Buffered Lidocaine Syringes With and Without Epinephrine. [2016]

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

Parenteral Lidocaine for Complex Cancer Pain in the Home or Inpatient Hospice Setting: A Review and Synthesis of the Evidence. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Treatment of localized post-traumatic neuropathic pain in scars with 5% lidocaine medicated plaster. [2021]

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

Lidocaine overdose: another preventable case? [2019]

7. England pubmed.ncbi.nlm.nih.gov

Lidocaine toxicity secondary to local anesthesia administered in the community for elective circumcision. [2013]

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

Case reports: type I hypersensitivity to lidocaine. [2013]

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

Safety and Efficacy of a Needle-free Powder Lidocaine Delivery System in Pediatric Patients Undergoing Venipuncture or Peripheral Venous Cannulation: Randomized Double-blind COMFORT-004 Trial. [2018]

10. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Lidocaine-induced CNS toxicity--a case report. [2022]

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

Liquid chromatographic determination of lidocaine in serum. [2019]

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

Pharmacokinetics of Lidocaine and Its Metabolites Following Vaginal Administration of Lidocaine Gel to Healthy Female Subjects. [2018]

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

Pharmacokinetics of lidocaine and its deethylated metabolite: dose and time dependency studies in man. [2019]

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

Plasma concentrations of lidocaine resulting from instillation of lidocaine jelly into genitourinary tract prior to cystoscopy. [2022]