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

NCT06391125 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 202401099
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Syphilis Infection; Benzathine Penicillin Adverse Reaction

Keywords

Syphilis; Syphilis Treatment; Benzathine Penicillin G; Lidocaine

Outcome Measures

Primary Outcomes (6)

• 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

  10 minutes

• 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

  10 minutes

• 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

  10 minutes

• 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

  24 hours

• 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

  24 hours

• 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

  24 hours

Secondary Outcomes (2)

• Rate of Adverse reactions

  7 days

• Rate of Use of other pain medications

  24 hours

Study Arms (2)

Lidocaine + Benzathine Penicillin G Arm

EXPERIMENTAL

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.

Drug: Lidocaine

Normal Saline + Benzthine Penicillin G Arm

PLACEBO COMPARATOR

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.

Drug: normal Saline

Interventions

normal Saline DRUG

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

Normal Saline + Benzthine Penicillin G Arm

Lidocaine DRUG

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

Lidocaine + Benzathine Penicillin G Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

WashU Infectious Diseases Clinic

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 9802630 BACKGROUND

• 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.

  PMID: 25348878 BACKGROUND

• 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.

  PMID: 31646969 BACKGROUND

MeSH Terms

Conditions

Syphilis

Interventions

Saline Solution; Lidocaine

Condition Hierarchy (Ancestors)

Treponemal Infections; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Central Study Contacts

Joseph Cherabie, MD

CONTACT

7202858096; jcherabie@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Both participants and clinicians will be blinded to the contents of the syringe. The nurse filling the syringe will assign the syringes randomly to be injected into L or R gluteal muscle and will label them accordingly, logging the designation in a log book that will remain blinded until the analysis portion of the study. The participant will be blinded as they will receive one site of injection with lidocaine and the other with normal saline, serving as their own intervention and control group.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: March 20, 2024
• First Posted: April 30, 2024
• Study Start: July 1, 2024
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)