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

Syphilis Infection Clinical Trial

— LIMIT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06391125
• Other study ID #: 202401099
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 2024
• Est. completion date: February 2025

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: Joseph Cherabie, MD
• Phone: 7202858096
• Email: jcherabie[@]wustl.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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, we 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: February 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• Penicillin allergy (anaphylaxis)

• Lidocaine allergy (anaphylaxis)

• Second or third injection in series if patient requires 3x weekly injections for syphilis treatment

• Pregnancy

Related Conditions & MeSH terms

• Syphilis
• Syphilis Infection

Intervention

Drug:
• normal Saline
0.5ml normal saline solution added to prefilled 1.2 million units Benzathine Pencillin G syringe
• Lidocaine
0.5ml 1% lidocaine solution added to prefilled 1.2 million units Benzathine Pencillin G syringe

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

References & 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. — View Citation

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. — View Citation

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. Erratum In: J Eur Acad Dermatol Venereol. 2015 Jun;29(6):1248. J Eur Acad Dermatol Venereol. 2015 Jun;29(6):1248. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	Rate of Adverse reactions	To see if there are any adverse effects of adding 0.5 ml 1% lidocaine to prepackaged Benzathine Penicillin G	7 days
Secondary	Rate of Use of other pain medications	To assess use of other pain medications 24 hours post injection.	24 hours