Lidocaine for Syphilis

(LIMIT Trial)

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether lidocaine, a local anesthetic, can reduce the pain of benzathine penicillin G (BPG) injections, which are commonly used to treat syphilis. Participants will receive two injections—one with lidocaine and one without—to compare pain levels at the injection sites. The trial aims to determine if lidocaine makes the injection less painful. Adults with a confirmed syphilis diagnosis who are receiving their first injection in a treatment series may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using lidocaine with benzathine penicillin G (BPG) injections is generally safe. Studies have found that lidocaine effectively reduces the pain from BPG injections, which treat syphilis. For over 20 years, lidocaine has been safely used in Europe to make BPG injections less concentrated.

No serious safety issues have emerged in studies where lidocaine was used with BPG injections. Patients who received lidocaine typically felt less pain after the injection and did not experience additional side effects. This suggests that the combination of lidocaine and BPG is well-tolerated by patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about using lidocaine for syphilis because it offers a new approach to enhancing patient comfort during treatment. Typically, syphilis is treated with Benzathine Penicillin G, which can be painful when injected. By adding lidocaine, a local anesthetic, to the penicillin injection, this method aims to reduce the discomfort associated with the standard treatment. This combination could make the treatment more tolerable for patients, potentially improving adherence and outcomes.

What evidence suggests that lidocaine might be an effective treatment for reducing pain in syphilis injections?

This trial will compare the effects of adding lidocaine to benzathine penicillin G (BPG) shots with a control using normal saline. Studies have shown that adding lidocaine to BPG significantly reduces injection pain. Research indicates that patients experience less pain when lidocaine is mixed with BPG. Specifically, one study found that individuals who received lidocaine before their BPG shot reported much less pain than those who did not. Since 1998, the International Union against Sexually Transmitted Infections (IUSTI) has supported using lidocaine with BPG to reduce pain. This evidence suggests that lidocaine can make syphilis treatment with BPG more comfortable for patients. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11338166/

Evaluation of Combined Strategy to Reduce the Pain ... The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39171085/

Evaluation of Combined Strategy to Reduce the Pain ... Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/25/NCT06391125/Prot_000.pdf

Lidocaine with Intramuscular Injection of Benzathine ... A1 Study Abstract. There is evidence to suggest that lidocaine can help reduce the pain associated with.

4. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00396-1/fulltext

Local anaesthetic to reduce injection pain in patients who ... Evidence of moderate quality suggests that lidocaine mixed with BPG causes moderate to major clinically meaningful reduction in immediate, 5 ...

5. medicine.iu.edu medicine.iu.edu/blogs/the-beat/study-confirms-one-dose-of-penicillin-is-effective-for-early-syphilis

Study confirms one dose of penicillin is effective for early syphilis A single dose of penicillin is effective for treating early-stage syphilis infections, according to results of a multisite clinical trial ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S2589537024003961

Local anaesthetic to reduce injection pain in patients who ... Utilisation of local anaesthetics appears to be safe and may reduce immediate post-injection pain in individuals requiring treatment with BPG. Safety data is ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06391125

Lidocaine With Intramuscular Injection of Benzathine ... The study found that patients who received lidocaine injections before receiving bicillin reported significantly less pain compared to those who received ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11613468/

Barriers and facilitators of benzathine penicillin G adherence ... Lidocaine was found to be effective at reducing pain related to BPG injections in randomized controlled trials [61, 62]. A lack of trust in ...