Clinical trial NCT06391125: LIMIT Trial - Lidocaine With Intramuscular Injection of Benzathine Penicillin G for Treponema Pallidum Treatment
Official title: LIMIT Trial - Lidocaine With Intramuscular Injection of Benzathine Penicillin G for Treponema Pallidum Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Syphilis Infection
Benzathine Penicillin Adverse Reaction
Keywords: Syphilis
Syphilis Treatment
Benzathine Penicillin G
Lidocaine
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2024-04-30
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Pain Score (0-10) of Benzathine Penicillin G + Lidocaine Injection 10 minutes post injection
timeFrame: 10 minutes
measure: Mean Pain Score (0-10) of Benzathine Penicillin G + Saline Injection 10 minutes post injection
timeFrame: 10 minutes
measure: Relative difference of mean pain scores between injection types 10 minutes post injection
timeFrame: 10 minutes
measure: Mean Pain Score (0-10) of Benzathine Penicillin G + Lidocaine Injection 24 hours post injection
timeFrame: 24 hours
measure: Mean Pain Score (0-10) of Benzathine Penicillin G + Saline Injection 24 hours post injection
timeFrame: 24 hours
measure: Relative difference of mean pain scores between injection types at 24 hours post injection
timeFrame: 24 hours
Secondary outcomes:
measure: Rate of Adverse reactions
timeFrame: 7 days
measure: Rate of Use of other pain medications
timeFrame: 24 hours
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: WashU Infectious Diseases Clinic
state: Missouri
Study officials:
References:
citation: 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.
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.
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.