A Randomized, Comparison Study of L.M.X.4 Cream Versus J-Tip Needle-Free Injection System With Lidocaine in Children Undergoing In-Office Percutaneous Achilles Tenotomy for Clubfoot
Phase: PHASE4
Conditions: Clubfoot
Sponsor: Vanderbilt University Medical Center

Document Cover Page 
Study Title: Comparison Study of LMX4 Cream Versus J-Tip Needle Free Injection 
System with Lidocaine for In-Office PAT for Clubfoot 
 
NCT Number: NCT04766684 
 
Document Description: Protocol 
 
Document Date: 07/31/2023 

Protocol Version #:5 
 
 
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Protocol Date: 7/31/2023 
 
 
 
 
 
 
 
 
A Randomized, Comparison Study of L.M.X.4 Cream versus J-Tip 
Needle-Free Injection System with Lidocaine in Children Undergoing 
In- Office Percutaneous Achilles Tenotomy for Clubfoot 
 
 
 
 
 
Jeffrey Martus, MD, MS 
Associate Professor of Orthopaedic Surgery and Rehabilitation  
 
Dee Baddley, MS, CCLS 
Certified Child Life Specialist 
 
 
 
Monroe Carell Jr. Children’s Hospital at Vanderbilt 
Department of Orthopaedic Surgery 
 
Participating Site:  
Texas Scottish Rite Hospital for Children 
Site PI: Anthony Riccio, MD 
 
 
 
 
 
 
 
 
 
 

Protocol Version #:5 
 
 
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Table of Contents: 
 
Study Schema 
1.0 
Background 
2.0 
Rationale and Specific Aims 
3.0 
Previous Studies 
4.0 
Inclusion/Exclusion Criteria 
5.0 
Enrollment 
6.0 
Study Procedures 
7.0 
Risks of Investigational Agents/Devices (side effects) 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants 
or Others 
9.0 
Study Withdrawal/Discontinuation 
10.0 
Statistical Considerations 
11.0 
Privacy/Confidentiality Issues 
12.0 
Follow-up and Record Retention 
13.0 
References 
14.0 
Temperament Assessment Evidence 
15.0 
FLACC Scale Evidence 
 
 
 
 
 
 
 
 

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1.0 
Background 
 
Congenital idiopathic clubfoot is defined as “a complex foot deformity that occurs in an 
otherwise normal child” (Morcuende, Dolan, Dietz, & Ponseti, 2004). Despite idiopathic 
clubfoot being due to unknown causes and occurring in approximately every 1 in 1000 
live births, it is often easily treated (Ansar et.al, 2018). Ignacio V. Ponseti was the leading 
pioneer in researching and treating clubfeet in infants and his methods are widely used 
today.  “The Ponseti method is a safe and effective treatment for congenital idiopathic 
clubfoot and radically decreases the need for extensive corrective surgery” (Morcuende, 
Dolan, Dietz, & Ponseti, 2004). “This method involves weekly stretching of the deformity 
followed by application of a long-leg cast. All components of the deformity usually 
correct within 4 to 5 weeks with the exception of the equinus. A simple percutaneous 
tendoachilles tenotomy often is necessary to correct completely the equinus” 
(Morcuende, Dolan, Dietz, & Ponseti, 2004). “After the tenotomy, a final cast is applied 
and left in place for 3 weeks to allow for healing to occur in the correct position. When 
the last cast is removed, the patient is treated with abduction splinting with straight- 
last shoes and a Denis Browne-style bar set at 45 degrees external rotation for the 
normal foot and 70 degrees for the clubfoot. In bilateral cases both feet are set at 70 
degrees of external rotation. The protocol for this foot abduction orthosis is 23 hours 
per day for the first 3 months and then nighttime only for 2 to 4 years. This process is 
essential to avoid recurrence” (Herzenberg, Radler, & Bor, 2002) “The goal of treatment 
is to correct all components of the deformity so that the patient has a pain-free, 
plantigrade foot with good mobility, without calluses, and without the need to wear 
special or modified shoes in the future” (Morcuende, Dolan, Dietz, & Ponseti, 2004). 
Several studies have supported Ponseti’s methods of casting and discovered positive 
results, primarily avoiding Posteromedial Release (PMR), an extensive open surgery 
(Herzenberg, Radler, Bor, 2002). This treatment also resulted in a decreased number of 
patients whose clubfoot relapsed following treatment by the Ponseti method 
(Morcuende, Dolan, Dietz, & Ponseti, 2004).  
 
 
One defining characteristic to Ponseti’s method is the addition of the percutaneous 
Achilles Tenotomy a small procedure which has been shown to avoid PMR in 95% of 
cases. Because PMR was found to lead to long term stiffness and weakness and involved 
greater surgical intervention, the percutaneous Achilles tenotomy was implemented 
(Herzenberg, Radler, Bor, 2002). The percutaneous Achilles Tenotomy entails releasing 
the tendon with a scalpel blade and dorsiflexing the foot in order to correct the equinus, 
followed by the application of a long leg cast (Lebel et. Al, 2012) (Morcuende, Dolan, 
Dietz, & Ponseti, 2004). Percutaneous Achilles Tenotomies have been successfully 
performed in the operating room under general anesthesia and in an outpatient clinic 
setting utilizing local or topical anesthesia. Ponseti and others have performed the 
procedure as an in-office procedure under sterile conditions, yielding a rate of 
successful “nonsurgical” correction of clubfoot approaching 90% of cases.” Performing 
this procedure in office has proven to be safe, yielding a low number of post-operative 
emergency room visits due to complications or parental concerns (Lebel et. Al, 2012).  

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While studies have shown that in office percutaneous achilles tenotomies are safe and 
efficient, little has been done to investigate the pain management strategies 
implemented for infants during this procedure. As healthcare professionals working 
with infants, “the prevention of pain in neonates should held as highly as the treatment 
being provided not only because it is ethical, but also because research has proven that 
repeated painful exposures during early stages of life have the potential for deleterious 
consequences” (American Academy of Pediatrics, 2016). Those consequences include, 
but aren’t limited to, “alterations in hemodynamic stability, altered stress hormone 
expression, heightened peripheral sensitivity, altered pain reactivity that persists 
following the painful stimulus, and somatization” (Stevens et. Al, 2014) One study 
identified the infant’s ability to become conditioned to painful stimuli, such as heel 
lances, at as early as 3 days old (Taddio, Shah, Gilbert-MacLeod, & Katz, 2002). With this 
information in mind, healthcare providers should be prepared to provide adequate pain 
management for infants during painful procedures by utilizing non-pharmaceutical 
techniques, pharmaceutical techniques, or a combination of both.  
 
During in office percutaneous Achilles tenotomies, several studies mention the use of 
topical anesthesia, such as EMLA, a Lidocaine/Prilocaine cream. This cream is applied to 
the infant’s skin surrounding the heel cord and requires 30 minutes to provide 
numbness reaching a depth of up to 5 mm at maximum effect (Fox, Tobin, & Aria, 2016). 
Pershad, Steinberg, & Waters, 2008, study reported that a 5-gram tube of ELMA cream 
cost the hospital $7.69, regardless of volume used from the tube. Other institutions 
have reported 25 grams of EMLA cream reaching $56.00. Due to clinical observation and 
medical advancements, there is room to believe that time efficient and cost-effective 
methods of providing greater pharmaceutical pain management to clubfoot infants 
during this procedure are available.  
 
The J-tip is a needle-free jet injection system that uses compressed CO2 instead of a 
needle to push .25 ml of lidocaine into the skin, providing a local anesthetic at the site of 
administration in less than a minute” (Lunoe, et al., 2015). The J-tip provides numbness 
to the site of application at a depth of 5- 8 mm (Fox, Tobin, & Aria, 2016). Pershad, 
Steinberg, & Waters, 2008, reported, in the same study referencing EMLA cream prices, 
that the Needle-free jet injection device price per cartridge and .25 mL of buffered 
Lidocaine cost the hospital $2.10.  Through various studies, the J-Tip has been proven to 
provide greater pain management than other pharmaceutical options, including EMLA 
cream and vapocoolant spray (Spanos, et al. 2008).  
 
2.0 
Hypothesis and Specific Aims 
 
Aim 1: Determine which pain management method, L.M.X.4 Cream vs. J-tip 1% Xylocaine 
MPF Injection, provides the greatest pain relief to infants with clubfoot undergoing an in-
office percutaneous TAL.   

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Hypothesis: J-tip 1% Xylocaine MPF injection will provide equal or greater pain control 
when compared to L.M.X.4 cream in infants undergoing an in-office percutaneous TAL.  
 
Aim 2: Determine if there is a difference in the rate of adverse events between the two 
pain management methods, L.M.X.4 Cream vs. J-tip 1% Xylocaine MPF Injection. 
Hypothesis: J-tip 1% Xylocaine MPF injection will not be associated with an increased rate 
of adverse events in comparison to L.M.X.4 cream in infants undergoing an in-office 
percutaneous TAL. 
 
3.0 
Animal Studies and Previous Human Studies 
 
The below studies reference 4% ELA-Max cream and EMLA cream. ELA-Max is the 
former name of L.M.X.4 cream.  EMLA cream is similar to the L.M.X.4 cream used by 
Vanderbilt Pediatric Orthopaedic physicians during routine care tenotomies for pain 
relief.  L.M.X.4 cream is an over the counter medication with an active ingredient of 
Lidocaine 4%. EMLA cream is a prescription only medication with active ingredients of 
Lidocaine 2.5%/Prilocaine 2.5%.   
 
Pediatr Emerg Care. 2008 Aug;24(8):511-5. doi: 10.1097/PEC.0b013e31816a8d5b. 
Jet Injection of 1% buffered lidocaine versus topical ELA-Max for anesthesia before 
peripheral intravenous catheterization in children: a randomized controlled trial. 
Spanos S, Booth R, Koenig H, Sikes K, Gracely E, Kim IK. 
 
Abstract 
BACKGROUND: 
Peripheral intravenous (PIV) catheter insertion is a frequent, painful procedure that is 
often performed with little or no anesthesia. Current approaches that minimize pain for 
PIV catheter insertion have several limitations: significant delay for onset of anesthesia, 
inadequate anesthesia, infectious disease exposure risk from needlestick injuries, and 
patients' needle phobia. 
OBJECTIVE: 
Comparison of the anesthetic effectiveness of J-Tip needle-free jet injection of 1% 
buffered lidocaine to the anesthetic effectiveness of topical 4% ELA-Max for PIV 
catheter insertion. 
METHODS: 
A prospective, block-randomized, controlled trial comparing J-Tip jet injection of 1% 
buffered lidocaine to a 30-minute application of 4% ELA-Max for 
topical anesthesia in children 8 to 15 years old presenting to a tertiary care pediatric 
emergency department for PIV catheter insertion. All subjects recorded self-reported 
visual analog scale (VAS) scores for pain at time of enrollment and pain felt following PIV 
catheter insertion. Jet injection subjects also recorded pain of jet injection. Subjects 
were videotaped during jet injection and PIV catheter insertion. Videotapes were 
reviewed by a single blinded reviewer for observer-reported VAS pain scores for jet 
injection and PIV catheter insertion. 

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RESULTS: 
Of the 70 children enrolled, 35 were randomized to the J-Tip jet injection group and 35 
to the ELA-Max group. Patient-recorded enrollment VAS scores for pain were similar 
between groups (P = 0.74). Patient-recorded VAS scores were significantly different 
between groups immediately after PIV catheter insertion (17.3 for J-Tip jet injection vs 
44.6 for ELA-Max, P < 0.001). Blinded reviewer assessed VAS scores for pain after PIV 
catheter insertion demonstrated a similar trend, but the comparison was not 
statistically significant (21.7 for J-Tip jet injection vs 31.9 ELA-Max, P = 0.23). 
CONCLUSION: 
J-Tip jet injection of 1% buffered lidocaine provided greater anesthesia than a 30-minute 
application of ELA-Max according to patient self-assessment of pain for children aged 8 
to 15 years undergoing PIV catheter insertion. 
TRIAL REGISTRATION: ClinicalTrials.gov NCT00444756. 
 
Acad Emerg Med. 2018 Mar;25(3):310-316. doi: 10.1111/acem.13351. Epub 2017 Dec 
26. A Randomized Double Blind Trial of Needle-free Injected Lidocaine Versus Topical 
Anesthesia for Infant Lumbar Puncture. 
Caltagirone R Raghavan VR, Adelgais K, Roosevelt GE. 
 
OBJECTIVES: 
Lumbar punctures (LPs) are commonly performed in febrile infants to evaluate for 
meningitis, and local anesthesia increases the likelihood of LP success. Traditional 
methods of local anesthesia require injection that may be painful or topical application 
that is not effective immediately. Recent advances in needle-free jet injection may offer 
a rapid alternative to these modalities. We compared a needle-free jet-injection system 
(J-Tip) with 1% buffered lidocaine to topical anesthetic (TA) cream for local anesthesia in 
infant LPs. 
METHODS: 
This was a single-center randomized double-blind trial of J-Tip versus TA for infant LPs in 
an urban tertiary care children's hospital emergency department. A computer 
randomization model was used to allocate patients to either intervention. Patients aged 
0 to 4 months were randomized to J-Tip syringe containing 1% lidocaine and a placebo 
TA cream or J-Tip syringe containing saline and TA. The primary outcome was the 
difference between the Neonatal Faces Coding Scale (NFCS) before the procedure and 
during LP needle insertion. Secondary outcomes included changes in heart rate (HR) and 
NFCS throughout the procedure, difficulty with LP, number of LP attempts, provider 
impression of pain control, additional use of lidocaine, skin changes at LP site, and LP 
success. 
RESULTS: 
We enrolled 66 subjects; 32 were randomized to J-Tip with lidocaine and 34 to EMLA. 
Six participants were excluded from the final analysis due to age greater than 4 months, 
and the remaining 58 were analyzed in their respective groups (32 J-Tip, 34 TA). There 
was no difference detected in NFCS between the two treatment groups before the 
procedure and during needle insertion for the LP (p = 0.58, p = 0.37). Neither HR nor 

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NCFS differed among the groups throughout the procedure. Median perception of pain 
control by the provider and the need for additional lidocaine were comparable across 
groups. LPs performed with a J-Tip were twice as likely to be successful compared to 
those performed using TA (relative risk = 2.0; 95% confidence interval = 1.01-3.93; 
p = 0.04) with no difference in level of training or number of prior LPs performed by 
providers. 
CONCLUSIONS: 
In a randomized controlled trial of two modalities for local anesthesia in infant LPs, J-
Tip was not superior to TA cream as measured by pain control or physiologic changes. 
Infant LPs performed with J-Tip were twice as likely to be successful. 
TRIAL REGISTRATION: 
ClinicalTrials.gov NCT01628874. 
 
J Pediatr Nurs. 2017 Nov - Dec;37:91-96. doi: 10.1016/j.pedn.2017.08.025. Epub 2017 
Aug 18. Comparison of Children's Venipuncture Fear and Pain: Randomized Controlled 
Trial of EMLA® and J-Tip Needleless Injection System®. 
Stoltz P, Manworren RCB. 
 
PURPOSE: 
Needle procedures, like venipuncture and intravenous (IV) catheter insertion, are 
recognized as a common cause of pain and fear for children in hospitals and emergency 
departments. The purpose of this study was to compare children's self-reported pain 
and fear related to IV insertion with administration of either the topical local 
anesthetic EMLA® or 1% buffered lidocaine delivered with the J-Tip Needleless Injection 
System® (J-Tip®). 
DESIGN AND METHODS: 
In this prospective, randomized trial, 150 consecutive pediatric patients 8 to 18years of 
age undergoing IV insertion were randomly assigned 1:1 to treatment group. 
Participants self-reported procedural pain using a Visual Analog Scale, and procedural 
fear using the Children's Fear Scale. 
RESULTS: 
Procedural pain scores were significantly lower in the EMLA® group (mean score 
1.63+1.659) vs. the J-Tip® group (2.99±2.586; p<0.001). Post-procedure fear scores were 
significantly lower than pre-procedure fear scores in both treatment groups (p<0.002), 
but there was no difference in fear scores between the two treatment groups (p=0.314). 
CONCLUSION: 
EMLA® provided superior pain relief for IV insertion compared to J-Tip®. 
PRACTICE IMPLICATIONS: 
Although EMLA® use resulted in lower self-reported pain scores compared to J-Tip®, 
pain scores for both treatments were low and fear scores did not differ. When IV 
insertion can be delayed for 60-90min, EMLA® should be used. When a delay is 
contraindicated, J-Tip® may be a reasonable alternative to minimize procedural pain of 
IV insertion. 
 

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Anesth Analg. 2006 Feb;102(2):411-4. 
A comparison of a needle-free injection system for local anesthesia versus EMLA for 
intravenous catheter insertion in the pediatric patient. 
Jimenez N, Bradford H, Seidel KD, Sousa M, Lynn AM. 
Abstract 
Placement of IV catheters is a painful and stressful procedure for children. J-Tip is a 
needle-less Food and Drug Administration approved injection system that can be used 
for delivery of local anesthetic before IV cannulation. In this study, we compared the 
effectiveness of J-Tip versus eutectic mixture of local anesthetics (EMLA) to facilitate IV 
cannulation and provide adequate analgesia before IV placement. Children 7-19 years of 
age (n = 116) were randomized to receive 0.25 mL of 1% buffered lidocaine with J-Tip (n 
= 57) or 2.5 g of EMLA (n = 59) before IV cannulation. Measurements of success of 
cannulation (number of attempts for IV placement) and pain (0-10 visual analog scale) at 
application of local anesthetic and at cannulation were performed. There was a 
significant (P = 0.0001) difference in pain ratings during IV cannulation 
between EMLA (median = 3) and the J-Tip (median = 0). Eighty-four percent of patients 
reported no pain at the time of J-Tip lidocaine application compared to 61% in 
the EMLA group at the time of dressing removal (P = 0.004). We did not find differences 
in the number of attempts for IV cannulation. J-Tip application of 1% 
buffered lidocaine before IV cannulation is not painful and has better anesthetic 
effectiveness compared with EMLA. 
 
Study personnel is not aware of any previous studies comparing J-Tip with 1% Buffered 
Lidocaine to EMLA cream for pain management in infants with clubfoot undergoing a 
percutaneous Achilles tenotomy. 
 
4.0 
Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
• Clubfoot patients less than 6 weeks of age at start of casting 
• Patients presenting to Vanderbilt DOT 4 Clinic for care 
• Patients undergoing in-clinic Achilles Tenotomy  
 
Exclusion Criteria 
• Clubfoot patients greater than 6 weeks of age at the start of casting 
• Previous clubfoot treatment 
• Patients with a neuromuscular condition (spina bifida, caudal regression 
syndrome, arthrogryposis, etc.)  
• In-office TAL is not recommended by treating physician due to patient factors 
such as age or size 
 
5.0 
Enrollment/Randomization 
 

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Enrollment 
 
General inclusion/exclusion criteria will be used to determine patient eligibility 
for this study.  Potential study participants will be identified when they present 
to the Vanderbilt Children’s Orthopaedic or Texas Scottish Rite Hospital for 
Children clinics for treatment of presumed congenital idiopathic clubfoot.   
 
In-person Consent Process 
When a patient is determined to be eligible for the study, study personnel will 
approach the patient’s parent(s)/legal guardian(s) about taking part in the study.  
If the patient’s parent(s)/legal guardian(s) agree for their child to participate in 
the study, they will be provided with an informed consent document to review. 
The consent process will be conducted using either 1) a paper version of the 
appropriate consent form or 2) a REDCap-based electronic consent form.  The 
electronic consent form has been developed in REDCap, a secure, web-based, 
HIPAA-compliant, data collection platform with a user management system. The 
REDCap-based electronic consent form can be accessed by research personnel 
using any electronic device.  They will be given an opportunity to ask questions 
about the study.  If the patient’s parent(s)/legal guardian(s) agree for their child 
to participate in the study by signing the informed consent document, they will 
be provided with a copy of the signed consent form for their records.   Only one 
parent/legal guardian signature will be required for this study.  
 
Electronic Consent Process: 
In the event a potential study candidate is missed during a clinic visit, or research 
personnel are unavailable to consent in-person, study personnel will contact the 
patient’s parent(s)/legal guardian(s) by phone to notify them of their child’s 
study eligibility and ask if they would be interested in their child taking part. If 
the parent(s)/legal guardian(s) are interested in their child taking part in the 
study, study personnel will send a link to the REDCap-based electronic consent 
form by e-mail.  If the parent(s)/legal guardian(s) agree for their child to take 
part in the study after reading the informed consent document, there will be an 
option for one parent/legal guardian to electronically sign their name and date 
the informed consent document.  Once they electronically sign the electronic 
informed consent document, they will be given an option to save or print the 
signed electronic informed consent documents for their files.  
 
We will seek to enroll 47 patients per group, 94 patients total in this study at 
each site.   
 
Randomization 
 
The patients will be randomized in equal proportion (1:1) to either the control 
group (receive L.M.X.4 cream with J-Tip saline injection) or the intervention 

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group (placebo cream with J-Tip with 0.25mL of 1% Xylocaine MPF).  
Randomization will take place on or after the final casting visit.  A randomization 
allocation table created by statisticians will be uploaded into REDCap.  The 
research coordinator will access the randomization module in REDCap and 
randomize the participant.   Patients will not be randomized until they are 
definitively diagnosed with congenital idiopathic clubfoot that requires a 
tenotomy and consented for participation in the study.   
 
6.0 
Study Procedures 
 
Weekly Casting Visits  
 
Once study consent is obtained, the subject will undergo serial casting weekly by one of two 
board-certified Pediatric Orthopaedic surgeons using the Ponseti method to address their 
congenital idiopathic clubfoot. CCLS will be present to provide coping support and 
standardize the environment. This is routine care at our institution.  During these castings, 
patient will wear pulse ox on hand, with mitten covering tool if needed, in order to measure 
heart rate and oxygen saturation. The CCLS, with assistance from a trained research 
assistant, will assess the subject’s pain and temperament utilizing observational data and 
data collected from FLACC Scale. Observational assessment is also routine care, but the 
FLACC data, pulse ox and temperament questionnaire are new, being collected strictly for 
the study. Primary data will be obtained during casting of first foot and, in the case of 
bilateral clubfoot patients, a subgroup will be created utilizing data collected during casting 
of both feet.    
 
Data collection during weekly castings will be obtained by a trained research assistant and 
will be event based, utilizing pulse ox and FLACC scale. Time points are as follows:  
• Baseline before cast placement (patient placed on treatment table) 
• Start of casting, after cast padding placed (1st cast if bilateral) 
• End of casting (2nd cast if bilateral) 
 
If the subject does not require tenotomy after the weekly casting, they will be withdrawn 
from the study. 
 
Casting Visit 1 Week Prior to Tenotomy 
 
During the final casting visit prior to the subject’s tenotomy, the subject’s temperament will 
be assessed by the parents and CCLS by utilizing: 
• An adapted temperament questionnaire for parents (research only) 
• Assessment of subject over time by CCLS utilizing FLACC scale, O2, HR and chart notes.  
 
On the day of or after the final casting visit, the participant will be randomized in equal 
proportion (1:1) to either the control group (receive L.M.X.4 cream with J-Tip saline 
injection) or the intervention group (placebo cream with J-Tip with 0.25mL of 1% Xylocaine 

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MPF). Researchers, physicians, nurses, CCLS, caregivers, and patients will be blinded to 
which group the patient is randomized.  The only person who will remain unblinded is the 
research coordinator.  
 
The Vanderbilt Investigational Drug Service will provide the 1% Xylocaine MPF,saline vials, 
L.M.X.4 and placebo creams.  The Investigational Drug Service will store, blind and dispense 
the creams and the J-Tip vials.   
 
Tenotomy 
 
On the day of the subject’s tenotomy they will receive pain control based on their group 
assignment- L.M.X.4 cream (with J-Tip Saline) or J-Tip with 0.25mL of 1% Xylocaine MPF 
(with placebo cream).  The treating physician will provide a Dimeglio score.  The following 
procedures will take place:  
• Baseline: FLACC and pulse ox data will be recorded as baby is positioned on 
treatment table 
• Application of randomized topical cream (either L.M.X.4 or placebo cream) for 30 
minutes timed.   
• Peak FLACC and pulse ox data will be recorded within 5 seconds of application of 
LMX 4 or Placebo Cream 
• Consent for tenotomy procedure will be obtained (routine care). 
• Baseline #2: FLACC and pulse ox data will be recorded 30 minutes after cream 
application 
• Parents will leave room (routine care). 
• Patient stays with healthcare staff (Physician, nurse, CCLS, cast tech, trained 
research assistant) 
• Cream will be removed from the subject’s foot (routine care). Peak FLACC and Pulse 
Ox will be recorded within 5 seconds after cream removal.  
• Baseline #3: FLACC and pulse ox data will be recorded 30 seconds after cream 
removal  
• J-Tip injection with 1% Xylocaine MPF or saline.  Peak FLACC scale measurements 
and pulse ox measurements will be recorded within 5 seconds of injection (1st foot if 
bilateral) 
• Following J-Tip injection there will be a 3-minute break, baby will be calmed during 
this time. 
• Baseline #4: FLACC scale measurements and pulse ox measurements 3 minutes after 
J-Tip injection 
• Tenotomy will be performed 
o FLACC Scale data and Pulse Ox data will be measured during the following 
events:  
 Percutaneous incision for TAL (1st foot if bilateral)- Peak FLACC scale and 
Pulse Ox data will be recorded within 5 seconds of poke of scalpel 
 Start of casting, after cast padding placed (1st cast if bilateral) 

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 End of casting (2nd cast if bilateral) 
 
Adverse local effects of the cream and/or J-Tip injection will be noted (skin redness, 
swelling, rash, etc).  Procedural complications will be recorded (excessive bleeding, 
concern for neurovascular injury, etc). 
 
Post-Tenotomy  
 
 
REDCap Text Message Survey Collection 
The subject’s parents will receive a text or email message requesting they complete a 
REDCap survey 1, 7, 14, and 21 days after the tenotomy.  They will be asked about the 
subject’s pain level, irritability, doses of Tylenol administered, and any other problems 
that their child is having due to the procedure. 
 
 
Clinical Visit around 21 days post-tenotomy (This visit is part of subject’s routine care) 
The subject will be assessed for complications. The treating physician will provide a 
Dimeglio score. A parental survey will be administered regarding quality of care, 
postoperative care, and perception of subject’s pain level. 
 
 
 
 
 
 
 
 
 
Routine Care 
 
 
REDCap Survey questions to be sent to parents post TAL 
REDCap Survey 
Postop Day 1 
1. On a scale of 1-5, with 1 being no pain and 5 being extreme 
pain, how much pain is your child having today due to the 
procedure? 
2. On a scale of 1 to 5, with 1 being no irritability and 5 being 
extreme irritability, how irritable is your child today due to the 
procedure? 
3. How many doses of Tylenol (acetaminophen) has your child 
been given today due to pain from the procedure?  
4.  If applicable, please list any other problems that your child is 
having today, due to the procedure.  
REDCap Survey 
Postop Day 7, 14 
& 21  
1. On a scale of 1-5, with 1 being no pain and 5 being extreme 
pain, how much pain has your child had over the last week due to 
the procedure? 
2. On a scale of 1 to 5, with 1 being no irritability and 5 being 
extreme irritability, how irritable has your child been over the last 
week due to the procedure? 
3. On average, how many doses of Tylenol (acetaminophen) per 
day have been given to your child over the last week due to pain 
experienced from procedure?  
4.  If applicable, please list any other problems your child has had 
over the last week, due to the procedure.  

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All research activities will be conducted during routine care visits.  The subject will not 
be asked to attend any research-only visits.  Serial casting and the tenotomy procedure 
are routine care.   
 
Standardizing the Environment 
 
The environment the subject experiences during their weekly casting visits, the day of the 
tenotomy, and POD 21 will be standardized to ensure observed behaviors are due to the 
procedures taking place and not related to new stimuli.  To standardize the environment 
the following will occur: 
 
• CCLS will be present 
• Casting by Moonlight (Turning off bright overhead lights, turning on small indirect 
light) 
• Developmentally appropriate coping strategies, such as oral sucrose, music, soothing 
touch, and Tranquilo Vibration Mat, will be implemented upon CCLS, family, and or 
healthcare staff’s discretion. The study is not limited to the following examples of 
coping strategies.  
 
Schedule of Events  
 
Study procedures 
Enrollment 
Visit 
Weekly 
Casting 
Visits 
Final 
Casting 
Visit (1 
week 
prior to 
tenotomy)  
Day of 
Tenotomy 
POD1 POD7 POD14 POD 
21  
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Dimeglio Score 
X 
 
 
X (Prior to 
tenotomy) 
 
 
 
X 
FLACC Scale 
 
X 
X 
X 
 
 
 
 
HR and O2 Levels via Pulse Ox 
 
X 
X 
X 
 
 
 
 
CCLS Assessment of 
Temperament 
 
X 
X 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
Parental Assessment of 
Temperament 
 
 
X 
 
 
 
 
 
Application of J-Tip and 
L.M.X.4 Cream based on 
randomization assignment 
 
 
 
X 
 
 
 
 
Parental REDCap Survey 
 
 
 
 
X 
X 
X 
X 

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Protocol Date: 7/31/2023 
Adverse Event/Complication 
Review 
 
 
 
X 
 
 
 
X 
 
  
7.0 
Risks 
 
L.M.X.4 (4% Lidocaine) Topical Anesthetic Cream Risk 
L.M.X.4 cream, is a topical anesthetic cream that may cause rash, redness, irritation, or 
swelling at the site of application. There is a risk that this drug may cause problems with 
heart rhythm. 
 
J-Tip with 1% Xylocaine MPF Risks 
Xylocaine may cause rash, redness, irritation, or swelling.  There is a risk that this drug 
may cause problems with heart rhythm. 
 
Breach of Confidentiality Risk: 
During this study every attempt will be made to keep the patient’s protected health 
information (PHI) private. Most study data will be maintained in a Vanderbilt REDCap 
database.  Vanderbilt Redcap is a secure, web-based application for building and 
managing online databases.  The data obtained and stored in Redcap will only be 
accessible by research personnel.  Participating site, Texas Scottish Rite Hospital for 
Children, will be provided with access to the Vanderbilt REDCap database.  The 
participating site will be able to view their records in the database but will not be able to 
view Vanderbilt’s records.  Any data sent to non-key study personnel for statistical 
analysis will be de-identified (dates will be shifted using a Redcap feature).   Any physical 
study forms (ex. consent documents, surveys) will be kept in a locked cabinet in the 
principal investigator’s office].  All study data will be maintained for 6 years following 
study completion.  Following this 6 year period, the Redcap database will be archived 
and all physical study forms will be disposed of in shred-it confidentiality bins provided 
by VUMC. 
 
Benefits 
 
If it is determined that the utilization of the J-Tip system is equal to or more effective at 
reducing pain in infants undergoing a tenotomy than L.M.X.4 cream is, the potential 
benefits of this study may include better pain management in infants undergoing a 
tenotomy in the future. In addition, a reduction in the amount of time required to 
anesthetize the surgical area from 30 minutes with L.M.X.4 cream to 1-2 minutes with a 
J-Tip injection would decrease the overall length of the visit and cost of procedure, thus 
increasing quality, safety, and value.   
 
8.0 
Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants 
or Others 
 

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Protocol Date: 7/31/2023 
The relationship of each adverse event to treatment rendered as judged by the 
investigator will be recorded on the Adverse Event Report Form. Due to the nature of 
the procedure involved in this study, certain adverse events may be considered normal 
sequalae associated with the procedure and will only be recorded if additional 
treatment is required or considered to be clinically significant. See specific indications 
for expected adverse events/complications due to nature of diagnosis.  
 
Definitions  
An AE can be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of an investigational product, whether or not related to the 
investigational product.  
 
Reporting Adverse Events  
Any adverse event (clinical sign, symptom, or disease) temporally associated with the 
study treatment shall be documented in the adverse event (AE) CRF, except those 
events that are considered to be normal sequalae to the surgical procedure. All AE's 
meeting the above noted criteria are to be reported by the subject or observed by the 
Principal Investigator will be individually listed. The description of the event (confirmed 
diagnosis, if available), date of onset, date of resolution, action taken, severity and 
relationship to study treatment, and follow-up procedures will be reported. 
 
The adverse event will be recorded in standard medical terminology. Additionally, the 
Principal Investigator will evaluate all adverse events as follows: 
 
Action taken: whether or not the adverse event caused the subject to discontinue the 
study 
 
Severity, to be assessed based on the table below: 
 
AE Severity Description 
DEGREE 
DESCRIPTION 
Mild 
(Grade 1) 
Symptom(s) barely noticeable to subject or does not make subject 
uncomfortable; does not influence performance or functioning; 
prescription drug not ordinarily needed for relief of symptom(s) but 
may be given because of the nature of subject.  
 
Moderate 
(Grade 2) 
 
 
Symptom(s) of a sufficient severity to make subject uncomfortable; 
performance of daily activity is influenced; subject is able to continue 
in study; treatment for symptom(s) may be needed. 
 
 
Severe 
(Grade 3) 
 
 
Cause severe discomfort; symptoms cause incapacitation or 
significant impact on subject’s daily life; severity may cause cessation 

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Protocol Date: 7/31/2023 
of study participation; treatment for symptom(s) may be given and/or 
subject hospitalized 
 
Life Threatening 
(Grade 4) 
 
 
Extreme limitation in activity, significant assistance required; 
significant medical intervention/therapy required, hospitalization or 
hospice care required. 
 
Relationship to treatment to be graded as: 
 
AE Relationship Description 
RELATIONSHIP 
DESCRIPTION 
 
 
Not related 
Any reaction that does not follow a reasonable temporal 
sequence from administration of the study treatment AND that 
is likely to have been produced by the subject’s clinical state or 
other modes of therapy administered to the subject. 
 
 
Unlikely 
Any reaction that does not follow a reasonable temporal 
sequence from administration of the study treatment or that is 
likely to have been produced by the subject’s clinical state or 
other modes of therapy administered to the subject. 
 
 
Likely 
A reaction that follows a reasonable temporal sequence from 
administration of the study treatment OR that follows a known 
response pattern to the suspected treatment AND that could not 
be reasonably explained by the known characteristics of the 
subject’s clinical state or other modes of therapy administered to 
the subject. 
 
 
Definite 
A reaction that follows a reasonable temporal sequence from 
administration of the study treatment AND that follows a known 
response pattern to the suspected treatment AND that recurs 
with rechallenge, and/or is improved by changing treatment 
 
Serious Adverse Events (SAEs) 
Events are classified as serious if they meet any of the following criteria (in accordance 
with 21 CFR 812.3(s)) and the recommendations of International Conference on 
Harmonization [Federal Register, October 7, 1997, Vol. 62, No. 194, pp 52239-45]): 
i. Any death. 
ii. Any life-threatening event, i.e., an event that places the subject, in the view 
of the investigator at immediate risk of death from the event as it occurred 
(does not include an event that, had it occurred in a more severe form, might 
have caused death). 
iii. Any event that requires or prolongs in-patient hospitalization. 
iv. Any event that results in persistent or significant disability/incapacity. 
v. Any congenital anomaly/birth defect diagnosed in a child of a subject who 
participated in this study following the study procedure. 

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Protocol Date: 7/31/2023 
vi. Other medically important events that in the opinion of the investigator may 
jeopardize the subject or may require intervention to prevent one of the 
other outcomes listed in the definition above. 
vii. Any serious problem associated with the study treatment that relates to the 
rights, safety or welfare of study subjects. 
 
The Principal Investigator or a member of the research staff will report all SAEs to the 
Institutional Review Board (IRB) according to the reporting requirements. 
 
9.0 
Study Withdrawal/Discontinuation 
 
Participation in this study is voluntary.  If at any time a study participant wishes to be 
withdrawn from the study, they may do so by contacting any of the key study personnel 
and letting them know they withdraw their consent.  The date in which the participant 
withdraws their consent will be noted in their study file.  Any information gathered up 
to the point of consent withdrawal may still be used for research and reporting.  
 
Enrolled patients will be removed from the study if they are inconsistent with casting 
follow-up visits, noncompliant with treatment, or if the treating physician recommends 
TAL in the operating room due to specific patient factors, such as age or size.  
 
10.0 
Statistical Considerations 
 
Power Analysis 
A power analysis was conducted to determine the sample size needed to find a clinically 
meaningful difference of 2.5 point in the FLACC score (SD=3) between the two methods. 
With alpha=0.05, power=0.8, and and effect size d=.83, at least 24 patients per group 
are required (N=48). Assuming a 20% participant lost to follow-up rate, we will need to 
enroll 29 patients per group (N=58).   
 
An interim power analysis was conducted to determine the sample size to find a 
clinically meaningful difference of 2.0 points in the FLACC score between the two 
methods.  This was performed using the maximum SD of the FLACC score observations 
of the first 39 patients (SD=4.13).   With alpha=0.05 and power=0.8, at least 47 patients 
per group are required (N=94).  
 
 
Data Analysis 
FLACC, heart rate, and oxygen saturation will be measured at 10 distinct time points 
(Table 1) during serial casting and following in-office TAL. Changes in FLACC score, heart 
rate, and oxygen saturation will be compared between treatment and control cohorts 
utilizing a two-way ANOVA with a Geisser-Greenhouse correction for matched time 
measures. A Sidak’s multiple comparisons test will be utilized to assess differences 
between cohorts at each of the 10 time points assessed. To compare number of 

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Protocol Date: 7/31/2023 
complications between cohorts, data will be collected at 3-weeks post TAL and analyzed 
using a non-parametric Mann-Whitney test, given the ordinal nature of the data. Similar 
non-parametric analysis with correction for multiple comparisons between cohorts will 
be utilized to assess changes in responses to REDCap surveys. Statistical analysis will be 
conducted utilizing GraphPad Prism 8.3.0. Statistical significance will be p<0.05.  
 
11.0 
Privacy/Confidentiality Issues 
 
During this study every attempt will be made to keep the patient’s protected health 
information (PHI) private. Most study data will be maintained in a Vanderbilt REDCap 
database.  Vanderbilt Redcap is a secure, web-based application for building and 
managing online databases.  The data obtained and stored in Redcap will only be 
accessible by research personnel.  Participating site, Texas Scottish Rite Hospital for 
Children, will be provided with access to the Vanderbilt REDCap database.  The 
participating site will be able to view their records in the database but will not be able to 
view Vanderbilt’s records.  Any data sent to non-key study personnel for statistical 
analysis will be de-identified (dates will be shifted using a Redcap feature).  Study 
personnel will use VUMC Box to share research documents.  The VUMC Box study folder 
will only be accessible by research personnel.   Any physical study forms (ex. consent 
documents, case report forms) will be kept in a locked cabinet in the principal 
investigator’s office.  All study data will be maintained for 6 years following study 
completion.  Following this 6-year period, the Redcap database will be archived and all 
physical study forms will be disposed of in shred-it confidentiality bins provided by 
VUMC. 
 
12.0 
Follow-up and Record Retention 
 
The duration of this study will last until we have enrolled and completed follow-up on 
24 patients per group (N=48).  All study data will be maintained for 6 years following 
study completion.  Following this 6 year period, the Redcap database will be archived 
and all physical study forms will be disposed of in shred-it confidentiality bins provided 
by VUMC.   
 
13.0 
References 
 
Ansar, A., Rahman, A. E., Romero, L., Haider, M. R., Rahman, M. M., Moinuddin, M., … 
Hoque, D. M. E. (2018). Systematic review and meta-analysis of global birth prevalence 
of clubfoot: a study protocol. BMJ Open, 8(3). doi: 10.1136/bmjopen-2017-019246 
 
Fox, B., Towbin, R., & Aria, D., “Approach to Local Anesthesia in Children.” Applied 
Radiology, June 2016, appliedradiology.com/articles/approach-to-local-anesthesia-in-
children. 
 

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Herzenberg, J. E., Radler, C., & Bor, N. (2002). Ponseti Versus Traditional Methods of 
Casting for Idiopathic Clubfoot. Journal of Pediatric Orthopaedics, 22(4), 517–521. doi: 
10.1097/01241398-200207000-00019 
 
Lebel, E., Karasik, M., Bernstein-Weyel, M., Mishukov, Y., & Peyser, A. (2012). Achilles 
Tenotomy as an Office Procedure. Journal of Pediatric Orthopaedics, 32(4), 412–415. 
doi: 10.1097/bpo.0b013e31825611a6 
 
Lunoe, Maren M., et al. “A Randomized Clinical Trial of Jet-Injected Lidocaine to Reduce 
Venipuncture Pain for Young Children.” Annals of Emergency Medicine, vol. 66, no. 5, 
2015, pp. 466–474., doi:10.1016/j.annemergmed.2015.04.003. 
 
Morcuende, J. A., Dolan, L. A., Dietz, F. R., & Ponseti, I. V. (2004). Radical Reduction in 
the Rate of Extensive Corrective Surgery for Clubfoot Using the Ponseti Method. 
Pediatrics, 113(2), 376–380. doi: 10.1542/peds.113.2.376 
 
Prevention and Management of Procedural Pain in the Neonate: An Update 
COMMITTEE ON FETUS AND NEWBORN and SECTION ON ANESTHESIOLOGY AND PAIN 
MEDICINE Pediatrics Feb 2016, 137 (2) e20154271; DOI: 10.1542/peds.2015-4271 
 
Spanos, Stephanie, et al. “Jet Injection of 1% Buffered Lidocaine Versus Topical ELA-Max 
for Anesthesia Before Peripheral Intravenous Catheterization in Children.” Pediatric 
Emergency Care, vol. 24, no. 8, Aug. 2008, pp. 511–515., 
doi:10.1097/pec.0b013e31816a8d5b. 
 
Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and Hyperalgesia in Newborns 
Exposed to Repeated Heel Lances. JAMA. 2002;288(7):857–861. 
doi:10.1001/jama.288.7.857 
 
 
14.0 
Temperament Assessment Evidence 
 
“The Origin of Personality” by Thomas, Chess and Birch, 1970.  
• 
“Infants begin to express themselves as individuals from the time of birth.”  
• 
“[Thomas, Chess, & Birch] identified nine characteristics that could be reliably 
scored on a three point scale (medium, high and low). The set of ratings in these 
nine characteristics defines the temperament, or behavioral profile, of a child, 
and the profile is discernible even as early as the age of two or three months.”  
• 
“Children do show distinct individuality in temperament in the first weeks of life, 
independently of their parents’ handling or personality style. Our long term 
study has now established that the original characteristics of temperament tend 
to persist in most children over the years.”  

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Protocol Date: 7/31/2023 
• 
“[Thomas, Chess, & Birch] found that certain characteristics did cluster together 
and defined three general types of temperament: easy, difficult, and slow to 
warm up.”  
• 
“Behavior of a child reveals that he has a distinct temperament early in life. 
These reports taken from interviews with the parents of the children studied by 
the authors show that temperamental differences are apparent when a child is 
only two months old.” 
• 
Temperamental characteristics that are crucial to classifying a child as easy, slow 
to warm up, and difficult are rhythmicity, approach/ withdrawal, adaptability, 
intensity of reaction, and quality of mood.” ((we also included threshold of 
responsiveness)) 
• 
**We will take 6 of the 9 characteristic stages, including each of the 5 crucial 
characteristics, for our study. Results will be broken into subgroups 
 
15.0 
FLACC Evidence  
 
“Clinical Validation of FLACC: Preverbal Patient Pain Scale” by Manworren & Hynan, 
(2003) 
• Pediatric nurses used the FLACC scale to assess pain in 147 children under 3 
years of age who were hospitalized in the pediatric intensive care unit, post- 
anesthesia care unit, surgical/ trauma unit, hematology/ oncology unit, or infant 
unit. FLACC is an observational tool for quantifying pain behaviors. Facial 
expression, leg movement, activity, cry, and consolability are each scored 0-2 for 
a total FLACC score of 0-10. The FLACC measurements were done pre-analgesia, 
at predicted onset of analgesia, and at predicted peak analgesia.  
• This study found that the FLACC pain assessment tool is appropriate for 
preverbal children in pain from surgery, trauma, cancer, or other disease 
processes. The results support pediatric nurses’ clinical judgement to determine 
analgesic choice rather than providing distinct FLACC scores to guide analgesic 
selection.  
• This is the FLACC Scale.  We will be measuring “Face, Legs, Activity, Cry and 
Consolability” 
https://journals.lww.com/ajnonline/fulltext/2002/10000/pain_assessment_in_in
fants_and_young_children__the.24.aspx?casa_token=vHoSGXsRSCQAAAAA:g5n
V_LfIBDURPC5A_3WdRI1_sNt1-MfkyoQFWaqUjASHwfKHTiXftxU-
LCWSrW5kVgtC0ZL7JvAvgI-QRj4b6Os 
 
 
 
 
 

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