LIMIT Trial - Lidocaine With Intramuscular Injection of Benzathine Penicillin G for Treponema Pallidum Treatment
Phase: PHASE3
Conditions: Syphilis Infection, Benzathine Penicillin Adverse Reaction
Sponsor: Washington University School of Medicine

 
 
 
 
 
 
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LIMIT Trial - Lidocaine with Intramuscular 
Injection of Benzathine Penicillin G for 
Treponema pallidum Treatment   
 
 
 
Principal Investigator:   
Joseph Cherabie MD MSc  
 
 
 
 
Version Date: 1/25/24 
Version Number: 1 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
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TABLE OF CONTENTS 
 
A 
INTRODUCTION ................................................................................................................................. 4 
A1 
STUDY ABSTRACT ........................................................................................................................... 4 
A2 
PRIMARY HYPOTHESIS AND PURPOSE OF THE STUDY ..................................................................... 4 
B 
BACKGROUND ................................................................................................................................... 4 
B1 
PRIOR LITERATURE AND STUDIES, AND RATIONALE FOR THIS STUDY ............................................ 4 
C 
STUDY OBJECTIVES ......................................................................................................................... 5 
C1 
PRIMARY AIM ................................................................................................................................. 5 
C2 
SECONDARY AIM ............................................................................................................................ 5 
D 
INVESTIGATIONAL AGENT ........................................................................................................... 5 
D1 
PRECLINICAL DATA ........................................................................................................................ 5 
D2 
CLINICAL DATA TO DATE ............................................................................................................... 5 
D3 
DOSE RATIONALE AND RISK/BENEFITS .......................................................................................... 6 
E 
STUDY DESIGN ................................................................................................................................... 6 
E1 
OVERVIEW OR DESIGN SUMMARY .................................................................................................. 6 
E2 
SUBJECT SELECTION AND WITHDRAWAL ........................................................................................ 6 
2.a 
Inclusion Criteria ....................................................................................................................... 6 
2.a 
Exclusion Criteria ...................................................................................................................... 6 
2.b 
Ethical Considerations............................................................................................................... 6 
2.c 
Subject Recruitment Plans and Consent Process ...................................................................... 6 
2.d 
Randomization Method and Blinding ........................................................................................ 7 
2.e 
Risks and Benefits ...................................................................................................................... 7 
2.f 
Early Withdrawal of Subjects, Including When and How to Withdraw Subjects ...................... 8 
2.g 
Data Collection and Follow-up for Withdrawn Subjects .......................................................... 9 
E3 
STUDY DRUG .................................................................................................................................. 9 
3.a 
Description ................................................................................................................................. 9 
3.b 
Treatment Regimen .................................................................................................................... 9 
3.c 
Method for Assigning Subjects to Treatment Groups ................................................................ 9 
3.d 
Preparation and Administration of Study Drug......................................................................... 9 
3.e 
Subject Compliance Monitoring ................................................................................................ 9 
3.f 
Prior and Concomitant Therapy ................................................................................................ 9 
3.g 
Packaging ................................................................................................................................ 10 
3.h 
Blinding of Study Drug ............................................................................................................ 10 
3.i 
Receiving, Storage, Disposing and Return .............................................................................. 10 
F 
STUDY PROCEDURES ..................................................................................................................... 10 
F1 
SCREENING FOR ELIGIBILITY AND VISIT 1 (COMPLETED AT ONE VISIT) ........................................ 10 
F2 
VISIT 2 .......................................................................................................................................... 11 
F3 
SAFETY AND ADVERSE EVENTS .................................................................................................... 11 
3.a 
Safety Monitoring ..................................................................................................................... 11 
3.b 
Medical Monitoring ................................................................................................................. 11 
i 
Investigator only ....................................................................................................................................... 11 
3.c 
Definitions of Adverse Events .................................................................................................. 11 
3.d 
Classification of Events ............................................................................................................ 11 
i 
Relationship .............................................................................................................................................. 11 
ii 
Severity ..................................................................................................................................................... 11 
iii 
Expectedness ............................................................................................................................................ 11 

 
 
 
 
 
 
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3.e 
Data Collection Procedures for Adverse Events ..................................................................... 11 
3.f 
Reporting Procedures .............................................................................................................. 11 
3.g 
Adverse Event Reporting Period .............................................................................................. 12 
3.h 
Post-study Adverse Event ......................................................................................................... 12 
F4 
STUDY OUTCOME MEASUREMENTS AND ASCERTAINMENT .......................................................... 12 
F5 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES .......................................................... 12 
G 
STATISTICAL PLAN ........................................................................................................................ 12 
G1 
SAMPLE SIZE DETERMINATION AND POWER ................................................................................. 12 
G2 
INTERIM MONITORING AND EARLY STOPPING .............................................................................. 12 
G3 
ANALYSIS PLAN ............................................................................................................................ 12 
G4 
STATISTICAL METHODS ................................................................................................................ 13 
G5 
MISSING OUTCOME DATA ............................................................................................................. 13 
G6 
UNBLINDING PROCEDURES ........................................................................................................... 13 
H 
DATA HANDLING AND RECORD KEEPING ............................................................................. 13 
H1 
CONFIDENTIALITY AND SECURITY ................................................................................................ 13 
H2 
TRAINING ...................................................................................................................................... 13 
H3 
RECORDS RETENTION ................................................................................................................... 13 
I 
STUDY MONITORING, AUDITING, AND INSPECTING .......................................................... 13 
I1 
STUDY MONITORING PLAN ........................................................................................................... 13 
I2 
AUDITING AND INSPECTING .......................................................................................................... 13 
J 
STUDY ADMINISTRATION ............................................................................................................ 14 
J1 
ORGANIZATION AND PARTICIPATING CENTERS ............................................................................ 14 
J2 
FUNDING SOURCE AND CONFLICTS OF INTEREST .......................................................................... 14 
J3 
SUBJECT STIPENDS OR PAYMENTS ................................................................................................ 14 
J4 
STUDY TIMETABLE ....................................................................................................................... 14 
K 
PUBLICATION PLAN ....................................................................................................................... 14 
L 
REFERENCES .................................................................................................................................... 14 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
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A Introduction 
 
A1 Study Abstract 
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. 
 
A2 Primary Hypothesis and Purpose of the Study 
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? 
 
 
B Background 
 
B1 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 

 
 
 
 
 
 
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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.  
in the US.  
 
 
C Study Objectives 
 
C1 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.  
 
C2 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.   
 
 
D Investigational Agent  
 
D1 Preclinical Data 
1% lidocaine has been added as a solvent for BPG in other countries around the world.  
 
D2 Clinical Data to Date  
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 IUSTI European Guidelines for syphilis management, 
lidocaine has been used as a diluent for BPG since 1998. In the 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.  
 

 
 
 
 
 
 
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D3 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.  
 
 
E Study Design  
 
E1 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.  
 
E2 Subject Selection and Withdrawal  
 
2.a 
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  
 
2.a 
Exclusion Criteria  
• Penicillin allergy (anaphylaxis)  
• Lidocaine allergy (anaphylaxis)  
• Second or third injection in series if patient requires 3x weekly injections for 
syphilis treatment  
• Pregnancy 
 
2.b 
Ethical Considerations  
This study is comparing standard of care, of not adding lidocaine to prepackaged BPG 
syringes to the addition of 1% lidocaine, which may relieve pain at injection site. 
Individuals will receive on injection in each butt cheek, one with lidocaine and one 
without, and will serve as their own control population. Lidocaine is very commonly used 
and is quite a low risk medication, and the addition of lidocaine in now way affects the 
efficacy of BPG.  
 
2.c 
Subject Recruitment Plans and Consent Process 
Participants will be recruited from the Washington University St. Louis Oupatient 
Infectious Disease Clinic. Each patient who meets the inclusion criteria will be screened 
by clinic staff and asked if they would consider being a part of this study. They would 
then be referred to our clinical trials unit upstairs from the WashU Infectious Diseases 
clinic where they will meet with intake staff via warm handoff and be provided with 

 
 
 
 
 
 
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information on the study and a consent form. The consent form will be signed prior to the 
participant being included in the trial as well as any questions required will be answered. 
Individuals will have between 30-60 minutes to consider participation as they will need 
to receive treatment prior to them leaving clinic. Any patient will receive standard of care 
treatment regardless of their willingness to participate in this study and treatment will not 
be withheld if patients do not participate. Forms will be kept in a secure database via 
RedCap and treatment will be documented in the participant's chart. 
 
Consent process: 
1- Participants with confirmed syphilis (RPR and treponemal test positive) who are 
receiving their first treatment injection of bicillin will be screened for participation in 
study by infectious diseases clinicians, nurses, or Mas who interact with the patient 
during their injection visit. If patient is willing to participate, trial team will be notified. 
(15-30 minutes)  
2- Trial team will assess patient for inclusion/exclusion criteria and ask if would like to 
be part of clinical trial. (5 minutes)  
3- The participant will then be taken to a clinic room, and be shown the consent form. 
Study design will be explained to them including them receiving the same treatment they 
would normally but with one injection with 0.5 ml normal saline and one with 0.5 ml 1% 
lidocaine. They will then be asked if they have any questions and if they choose to 
consent, they will sign a physical consent form that will then be uploaded into their chart. 
(30-45 minutes)  
 
2.d 
Randomization Method and Blinding 
Both clinicians and participants will be blinded to the contents of the syringes. Only the 
nursing staff will know which syringe contains lidocaine and which contains normal 
saline as they will be drawing up the contents into the syringes, after which they will 
designate L and R on the syringes and in a log book which will designate which syringe 
had lidocaine and which had normal saline. This log book will be kept separate from 
clinicians and participants until study completion. Each participant will have a unique 
code that will be included in the log book, where the nurse who fills the syringes will 
state which side, left or right, contained lidocaine and which contained normal saline. 
This log book will then be used to cross reference injection sites and the survey results 
during the analysis phase, in a way that allows the data to be de-identified. 
 
2.e 
Risks and Benefits 
 
Risks 
Risks are rare and mainly involve injection site pain, allergic reaction. Some risks, if severe, may cause 
death.  
 
Likely / Common  
Mild 
• Pain at injection site (BPG) 
• Headache (lidocaine) 

 
 
 
 
 
 
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• Transient pain (lidocaine) 
• Edema (lidocaine) 
 
Less Likely / Less Common 
Mild 
• Hypersensitivity Rash (BPG) 
• Diarrhea (BPG) 
• Agitation (lidocaine) 
• Anxiety (lidocaine) 
• Confusion (lidocaine) 
• Dizziness (lidocaine) 
• Lethargy (lidocaine) 
• Tinnitus (lidocaine) 
 
Rare   
Life Threatening 
• Hypersensitivity- anaphylaxis (BPG and Lidocaine) 
Serious 
• Neutropenia (BPG high doses) 
• Hyperreflexia (BPG high doses) 
• Myoclonus (BPG high doses) 
• Seizure (BPG high doses) 
• Acute interstitial nephritis (BPG high doses) 
• Cardiac Arrhythmia (lidocaine) 
• Hypotension (lidocaine) 
• Seizure (lidocaine) 
• Bronchospasm, dyspnea (lidocaine) 
Mild 
• Hyperkalemia (BPG) 
 
There is a risk of breach of confidentiality. 
 
Benefits 
The potential benefit to the participant is that they would receive the treatment they 
normally would but with the potential benefit of less pain in the injection site with 1% 
lidocaine. As for the benefit to society, this may provide evidence that may change 
standard clinical practice with respect to how we perform benzathine penicillin G 
injections in the US and if lidocaine is shown to cause less pain, then it would become 
standard practice to include 1% lidocaine in each syringe of benzathine penicillin G.  
 
2.f 
Early Withdrawal of Subjects, Including When and How to Withdraw 
Subjects  
Early withdrawal of subjects will be handled by the principal investigator, with 
participants having the direct contact of the PI via email or phone, and through stating 
that they no longer would like to participate in the study. The PI also will have the right 

 
 
 
 
 
 
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to withdraw someone if upon evaluation of the patient, they meet certain exclusion 
criteria. All withdrawals will be done immediately and seeing as this study has short term 
of participation, withdrawal should not be difficult. 
 
 
2.g 
Data Collection and Follow-up for Withdrawn Subjects  
Individuals who withdraw from the study will be noted as lost to follow up and no further 
data will be obtained from them. They will continue to receive standard of care within the 
outpatient clinical setting.  
 
 
E3 Study Drug  
 
3.a 
Description  
1% lidocaine solution added to prefilled 1.2 million units Benzathine penicillin G.  
 
3.b 
Treatment Regimen  
0.5ml 1% lidocaine solution added to prefilled 1.2 million units Benzathine 
Pencillin G syringe 
 
3.c 
Method for Assigning Subjects to Treatment Groups  
Each participant will receive 2x 1.2 million units injection, one with lidocaine and 
one with normal saline, therefore each participant will serve as both treatment and 
control group.  
 
3.d 
Preparation and Administration of Study Drug  
Each syringe of BPG is prefilled. A nurse/MA will then add 0.5 ml 1% lidocaine 
solution to one BPG syringe, and 0.5ml normal saline solution to another BPG 
syringe. They will randomly syringes to be injected into the left gluteal muscle vs 
the right gluteal muscle via random assignment program. They will log the 
assignment with the unique patient code into a log book.  
 
3.e 
Subject Compliance Monitoring  
Each log book entry will be entered into RedCap survey using the unique patient 
code and then the patient will fill out pain scale in RedCap using their unique 
code 10 minutes and 24 hours after injection through follow up email. If they do 
not respond to the 24 hour follow up email, a second email will be sent 48 hours 
after injection.  
 
3.f 
Prior and Concomitant Therapy  
Participants will be asked in the follow up survey about any other pain 
medications they have taken within the last 24 hours. They will also be asked 
about if this is their first treatment with respect to syphilis treatment, or if this is 
the second or third dose in a series of treatment. No other concomitant therapies 
would preclude individuals from participating in the study.  
  

 
 
 
 
 
 
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3.g 
Packaging  
Both BPG syringes will look identical other than having one say L and one say R, 
based off randomization. 
 
3.h 
Blinding of Study Drug  
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.  
 
3.i 
Receiving, Storage, Disposing and Return  
BPG will be stored in the refrigerator in the Washington University St. Louis 
Infectious Diseases clinic, along with the lidocaine and normal saline solutions 
being kept in storage in the same clinic. All syringes will be disposed of in sharps 
containers, as well as used  lidocaine ampules and normal saline syringes.  
 
 
F Study Procedures  
 
F1 Screening for Eligibility and Visit 1 (completed at one visit) 
1- Participants with confirmed syphilis (RPR and treponemal test positive) who are 
receiving their first treatment injection of bicillin will be screened for participation in the 
study by infectious diseases clinicians, nurses, or Mas who interact with the patient 
during their injection visit. If patient is willing to participate, trial team will be notified. 
(15-30 minutes)  
2- Trial team will assess patient for inclusion/exclusion criteria and ask if would like to 
be part of clinical trial. (5 minutes)  
3- The participant will then be taken to a clinic room and be shown the consent form. 
Study design will be explained to them including them receiving the same treatment they 
would normally but with one injection with 0.5 ml normal saline and one with 0.5 ml 1% 
lidocaine. They will then be asked if they have any questions and if they choose to 
consent, they will sign a physical consent form that will then be uploaded into their chart. 
(30-45 minutes)  
  
4- Trial staff will then obtain the two injections and administer them one in each gluteal 
muscle. The patient will then be left for 15 minutes, after which they will fill out a pain 
score 0-10 for each injection site at 10 minutes post injection. (15-30 minutes)  
5- Patient will then be informed they will receive an email survey (via RedCap) 24 hours 

 
 
 
 
 
 
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11 
from trial staff to answer the same pain scale questions at that time. Exit counseling will 
occur and patient is then free to go. (15 minutes)  
 
F2 Visit 2  
Participants will receive an email from trial staff 24 hours after injection site to rate their 
pain from 0-10 at that time via online survey (RedCap) and to ask if any other pain 
medication was used in the last 24 hours and if they had any other symptoms/side effects. 
(5 minutes) 
 
F3 Safety and Adverse Events  
 
3.a 
Safety Monitoring 
Patients will be asked about other side effects/adverse events during the 24 hour 
follow up. Patients can also contact providers through MyChart and/or through 
contacting the clinic/trial team.  
 
3.b 
Medical Monitoring  
 
i 
Investigator only 
The investigator team will be monitoring the survey results for any signs of 
adverse effects. The monitoring will be ongoing and there will be an internal 
review of combined data every 6 months.  
 
3.c 
Definitions of Adverse Events 
Any undesirable experience associated with the use of medical product in patient. 
Common adverse events are listed above.  
 
3.d 
Classification of Events 
 
i 
Relationship 
10 minutes after injection vs. 24 hours after injection 
 
ii 
Severity 
Mild, Moderate, or life threatening 
 
iii 
Expectedness 
Rare, other than injection site pain which is common 
 
3.e 
Data Collection Procedures for Adverse Events 
Adverse events will be asked about in the survey given 24 hours post injection. 
 
3.f 
Reporting Procedures 
Participants will report adverse events via a RedCap survey emailed 24 hours post 
injection. Other adverse events can be reported to PI or to clinic staff. 
 

 
 
 
 
 
 
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3.g 
Adverse Event Reporting Period 
Adverse events can be reported within 7 days post injection with participants 
having the ability to call for up to 7 days.  
 
3.h 
Post-study Adverse Event 
Any adverse event post study or the time listed above should be reported to the PI.  
 
F4 Study Outcome Measurements and Ascertainment 
The primary outcome measure will be pain rating scores from 0 (least pain) to 10 
(most pain) at 10 minutes after injection in each injection site, as well as 24 hours 
after injection.  
 
Secondary outcome measures will include adverse effects of lidocaine or 
benzathine penicillin G., such as allergic reactions or injection site reactions. 
 
F5 Rationale for the Selection of Outcome Measures 
Injection site pain is the most common adverse effect of Benzathine Penicillin G 
(BPG) intramuscular injections. For this reason, rating pain scales from 0-1 10 
minutes and 24 hours after injection will allow us to measure immediate and longer 
term pain after injection, with and without lidocaine added to prefilled BPG 
syringes.  
 
 
G Statistical Plan  
 
G1  Sample Size Determination and Power 
A sample size of 46 patients (92 injections) will be required to detect a clinically 
significant reduction in pain and discomfort associated with the injection of 
Bicillin, with a power of 80% and a significance level of 0.05. 
 
G2  Interim Monitoring and Early Stopping 
As this is a short term study with small population, it is not expected to stop early. 
Interim monitoring for adverse effects will occur at 6 months or after 24 
participants have participated, whichever occurs first.  
 
G3  Analysis Plan 
Pain scores will be collected by trained study personnel. Data will be entered into a 
secure database and analyzed using statistical software. Descriptive statistics will be used 
to summarize the data, and t-tests or chi-squared tests will be used to compare pain scores 
and adverse effects between the treatment and control groups. They will also see if there 
any use of pain medications through descriptive statistics. Demographic data will also be 
collected.  
 

 
 
 
 
 
 
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G4  Statistical Methods  
Descriptive statistics will be used to summarize the data, and t-tests or chi-squared 
tests will be used to compare pain scores and adverse effects between the treatment 
and control groups. 
 
G5  Missing Outcome Data 
Missing outcome data on follow up will be noted and statistical analysis will be 
performed on intention to treat model.  
 
G6  Unblinding Procedures  
Unblinding will occur at the analysis stage to perform analysis and designate 
injections as being with lidocaine or with normal saline, and assigning the proper 
site of injection for each. This data will then be uploaded into RedCap for further 
analysis.  
 
 
H Data Handling and Record Keeping  
 
H1 Confidentiality and Security 
We will be using our electronic medical record as well as communicating via secure email with 
surveys being filled on RedCap. That survey information will be de-identified and will be saved 
on a secure database ensuring confidentiality.   
 
For paper records, these will be stored in a locked area. Access will be limited to research team 
members only. 
 
H2 Training  
See above  
 
H3 Records Retention 
Records will be retained for the length consistent with University requirements. 
 
 
I Study Monitoring, Auditing, and Inspecting  
 
I1 
Study Monitoring Plan  
Study monitoring will occur by the investigational team, with weekly check in on 
data gathering and logging of information into RedCap and log book.  
 
I2 
Auditing and Inspecting  
Weekly audits will occur of data obtained in log book and RedCap to ensure data 
safety, confidentiality, and study going according to protocol.  
 
 

 
 
 
 
 
 
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J Study Administration 
 
J1 Organization and Participating Centers 
Washington University St. Louis Infectious Diseases Clinic 
 
J2 Funding Source and Conflicts of Interest 
Participants insurance will be billed or they will be billed as standard of care is 
being provided. The cost of lidocaine and saline will be billed to insurance or 
patient accordingly. 
 
J3 Subject Stipends or Payments  
None 
 
J4  Study Timetable 
Ideally will complete data acquisition within 12 months 
 
 
K Publication Plan  
 
We plan to publish in academic peer reviewed journal such as Clinical Infectious 
Diseases or Sexually Transmitted Diseases.  
 
 
L References 
 
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.  
 
Janier, M., Hegyi, V., Dupin, N., Unemo, M., Tiplica, G.S., Potočnik, M., French, P. and 
Patel, R. (2014), 2014 European guideline on the management of syphilis. J Eur Acad 
Dermatol Venereol, 28: 1581-1593. https://doi.org/10.1111/jdv.12734  
 
Estrada, V., Santiago, E., Cabezas, I. et al. 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 19, 883 (2019). 
https://doi.org/10.1186/s12879-019-4490-5