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Syphilis InfectionPhase 3LIMITNCT06391125

LIMIT Trial - Lidocaine With Intramuscular Injection of Benzathine Penicillin G for Treponema Pallidum Treatment

A Phase 3 study testing normal Saline and Lidocaine in people with Syphilis Infection and Benzathine Penicillin Adverse Reaction, run by Washington University School of Medicine at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
What is being tested?
normal Saline and Lidocaine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
48 participants
Where
1 siteUnited States
Study dates
1 Jul 2024to Dec 2025
Phase
Phase 3
Are there results?
Not yet: the study is under way

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
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Adults 18 years of age or above
  • Confirmed syphilis diagnosis (reactive RPR with confirmatory treponemal testing)
  • Receiving first injection in series if patient requires 3x weekly injections for syphilis treatment

Who cannot join

  • Penicillin allergy (anaphylaxis)
  • Lidocaine allergy (anaphylaxis)
  • Second or third injection in series if patient requires 3x weekly injections for syphilis treatment
  • Pregnancy

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Joseph Cherabie, MD contact

7202858096

jcherabie@wustl.edu

United States1 site, 1 recruiting
  • WashU Infectious Diseases Clinic

    St Louis, Missouri, 63110

    Joseph N Cherabie, MD, 314-362-7827, jcherabie@wustl.edu

    Joseph N Cherabie, MD

    Recruiting

Other trials in United States

About this study

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.

Read the detailed description

The purpose of the study is to test the question of: Does the addition of 0.5ml 1% lidocaine compared to 0.5 ml normal saline solution to 1.2 million units of benzathine penicillin G affect the pain experienced by individuals being treated for Treponema pallidum (syphilis) infections at 10 minutes and 24 hours post injection?

Background

Prior Literature and Studies, and Rationale for this Study

There is evidence to suggest that lidocaine can help reduce the pain associated with intramuscular injections of benzathine penicillin G or bicillin, used to treat syphilis infections. A study published in the Journal of Pediatric Infectious Diseases in 1998 found that the use of lidocaine as a diluent of BPG significantly reduced the pain of injection. Another study by Estrada et al in 2019 looked at the addition of 1% mepivicaine as diluent for PGB vs PGB alone and showed that mepivicaine significantly decreased pain experienced by participants. Per the IUSTI European Guidelines for Syphilis management, lidocaine is used as a diluent for benzathine penicillin G since 1998. No studies have been performed thus far looking at prefilled benzathine penicillin G syringes and the possibility of inserting lidocaine to the injection to decrease the pain experienced by individuals being treated for syphilis infections, instead of using lidocaine as a diluent which is not possible for the BPG formulations present here in the US.

Study Objectives

Primary Aim To see if there is any benefit of adding 0.5 ml 1% lidocaine to prepackaged Benzathine Penicillin G, with respect to pain, compared to standard of care, in the treatment of Treponema pallidum infections, both 10 minutes and 24 hours after injection.

Secondary Aim To see if there are any adverse effects of adding 0.5 ml 1% lidocaine to prepackaged Benzathine Penicillin G and to assess use of other pain medications 24 hours post injection.

Dose Rationale and Risk/Benefits Use of 0.5 ml 1% lidocaine was decided upon based off the size of the prefilled BPG syringe and the room for additional liquid within the syringe. 1% lidocaine is commonly used as a pain relief measure in clinical settings for injections and other procedures.

Overview or Design Summary This study is a double blinded randomized placebo control trial of addition of the effect on pain of the addition of 0.5ml 1% lidocaine solution to prepackaged benzathine Penicillin G injection, compared to addition of 0.5 ml normal saline solution, in adults being treated for syphilis (Treponema pallidum) infections, within the Infectious Diseases Clinic at Washington University in St. Louis.

Being tested
normal Saline, Lidocaine
Keywords
Syphilis, Syphilis Treatment, Benzathine Penicillin G, Lidocaine
Medical subject headings
Syphilis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • normal SalineDrug

    0.5ml normal saline solution added to prefilled 1.2 million units Benzathine Pencillin G syringe

  • LidocaineDrug

    0.5ml 1% lidocaine solution added to prefilled 1.2 million units Benzathine Pencillin G syringe

Study groups in NCT06391125
Study groupRoleWhat they receive
Lidocaine + Benzathine Penicillin G ArmExperimental0.5ml 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.
Receives: Drug: Lidocaine
Normal Saline + Benzthine Penicillin G ArmPlacebo comparator0.5ml 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.
Receives: Drug: normal Saline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Pain Score (0-10) of Benzathine Penicillin G + Lidocaine Injection 10 minutes post injection

    The average rating of participants' injection site pain with added lidocaine from 0 (no pain) to 10 (extreme pain) at 10 minutes post injection

    Measured: 10 minutes

  2. Mean Pain Score (0-10) of Benzathine Penicillin G + Saline Injection 10 minutes post injection

    The average rating of participants' injection site pain with added lidocaine from 0 (no pain) to 10 (extreme pain) at 10 minutes post injection

    Measured: 10 minutes

  3. Relative difference of mean pain scores between injection types 10 minutes post injection

    Comparative t-test of means of pain scores at injections sites at 10 minutes post injection

    Measured: 10 minutes

  4. Mean Pain Score (0-10) of Benzathine Penicillin G + Lidocaine Injection 24 hours post injection

    The average rating of participants' injection site pain with added lidocaine from 0 (no pain) to 10 (extreme pain) at 24 hourspost injection

    Measured: 24 hours

  5. Mean Pain Score (0-10) of Benzathine Penicillin G + Saline Injection 24 hours post injection

    The average rating of participants' injection site pain with added lidocaine from 0 (no pain) to 10 (extreme pain) at 24 hours post injection

    Measured: 24 hours

  6. Relative difference of mean pain scores between injection types at 24 hours post injection

    Comparative t-test of means of pain scores at injections sites at 24 hours post injection

    Measured: 24 hours

Secondary outcomes (2)
  1. Rate of Adverse reactions

    To see if there are any adverse effects of adding 0.5 ml 1% lidocaine to prepackaged Benzathine Penicillin G

    Measured: 7 days

  2. Rate of Use of other pain medications

    To assess use of other pain medications 24 hours post injection.

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2024
  2. Study start1 Jul 2024
  3. Primary completionDec 2025 (estimated)
  4. Study completionDec 2025 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
double blinded randomized placebo control trial of addition of the effect on pain of the addition of 0.5ml 1% lidocaine solution to prepackaged benzathine Penicillin G injection, compared to addition of 0.5 ml normal saline solution, in adults being treated for syphilis (Treponema pallidum) infections, within the Infectious Diseases Clinic at Washington University in St. Louis.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06391125
Sponsor's protocol ID
202401099
Acronym
LIMIT
Status last verified
Mar 2025
First submitted
20 Mar 2024
Last updated
25 Mar 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Amir J, Ginat S, Cohen YH, Marcus TE, Keller N, Varsano I. Lidocaine as a diluent for administration of benzathine penicillin G. Pediatr Infect Dis J. 1998 Oct;17(10):890-3. doi: 10.1097/00006454-199810000-00008.

    PubMed 9802630
  • Janier M, Hegyi V, Dupin N, Unemo M, Tiplica GS, Potocnik M, French P, Patel R. 2014 European guideline on the management of syphilis. J Eur Acad Dermatol Venereol. 2014 Dec;28(12):1581-93. doi: 10.1111/jdv.12734. Epub 2014 Oct 27.

    PubMed 25348878
  • Estrada V, Santiago E, Cabezas I, Cotano JL, Carrio JC, Fuentes-Ferrer M, Vera M, Ayerdi O, Rodriguez C, Lopez L, Cabello N, Nunez MJ, Puerta T, Sagastagoitia I, Del Romero J. Tolerability of IM penicillin G benzathine diluted or not with local anesthetics, or different gauge needles for syphilis treatment: a randomized clinical trial. BMC Infect Dis. 2019 Oct 23;19(1):883. doi: 10.1186/s12879-019-4490-5.

    PubMed 31646969

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing normal Saline and Lidocaine in people with Syphilis Infection and Benzathine Penicillin Adverse Reaction, run by Washington University School of Medicine 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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 25 Mar 2025. 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Joseph Cherabie, MD (7202858096, jcherabie@wustl.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Pain Score (0-10) of Benzathine Penicillin G + Lidocaine Injection 10 minutes post injection (time frame: 10 minutes). The study lists 6 primary outcomes in all. 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 NCT06391125, which also lists 3 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 25 Mar 2025.

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