Clinical trial NCT03571737
Conditions: Acute Musculoskeletal Disease Sprains Sprains and Strains Injuries Emergencies Trauma Acute Pain
Keywords: acute pain muscle strain muscle sprain injury emergency department
Sponsor: East Carolina University
Start date: 2018-06-23; Completion date: 2021-01-30
Enrollment: 23 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluates the addition of a lidocaine patch to ibuprofen in the treatment of acute musculoskeletal pains. Half of the participants will get only ibuprofen for their pain, while other half will receive lidocaine patch plus the ibuprofen. After addition of the pain medications, the participants will be followed for their pain scores and return visits.

Detailed description:
Ibuprofen and other nonsteroidal antiinflammatory pain medications have been traditionally used for relief of mild to moderate acute musculoskeletal pains. However, if this medication did not work, a different modality for pain control would be added to the original regimen. In recent times, lidocaine patch has been introduced as a separate modality for pain control. This medication is thought to help by selectively inhibiting voltage-gated sodium channels in nociceptors involved in pain response. Given the separate modality, it would be prudent to see whether the addition of lidocaine patch to the ibuprofen would help relieve the pain more so than the antiinflammatory-only regimen.

Arms: arm 1: Ibuprofen 800mg every 8 hours for 3 days arm 2: Ibuprofen 800mg every 8 hours for 3 days and Lidocaine patch 4% 1 patch applied for 12 hours then removed for 12 hours, for 3 days
Interventions: intervention 1: Ibuprofen intervention 2: Lidocaine Patch 4%
Intervention descriptions: intervention 1: Ibuprofen tablet intervention 2: Lidocaine patch

Protocol documents:
SAP_002.pdf: 
Efficacy of Lidocaine Patch in Acute Musculoskeletal Pain in the Emergency Department: A 
Prospective Randomized Controlled Study. 
 
 
 
NCT03571737 
 
 
 
April 12, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
Statistical Plan 
 
Differences in pain scores will be analyzed using a one-tail t-test. With an a priori power 
analysis, we would like to see at least a 2-point difference in pain score 11, with minimally 
clinically significant difference of 1.3 points. To achieve this, we will need at least 140 patients 
total (70 in each arm). Alpha will be set at 0.05, with power of 90%. Allowing for error or 
patient dropping out, we request that 180 people be enrolled in the study.   In the study site, at 
least 682 patients in the month of March 2018 have come into the ED that were billed as having 
complaint of musculoskeletal pains.  
 

Prot_001.pdf: 
1 
 
Efficacy of Lidocaine Patch in Acute Musculoskeletal Pain in the Emergency Department: A 
Prospective Randomized Controlled Study. 
 
 
 
NCT03571737 
 
 
 
April 12, 2018 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Protocol 
Title: Efficacy of Lidocaine Patch in Acute Musculoskeletal Pain in the Emergency Department: 
A Prospective Randomized Controlled Study. 
Background and introduction: 
In 2014, musculoskeletal injuries accounted for about 10% of the emergency department visits in 
the nation for the year. 8 Analgesics comprise 30% of the prescriptions mentioned in the 
emergency department, comprising of both over-the-counter options as well as prescriptions. 8 
These analgesics alleviate the acute phase of pain while patients adhere to the standard treatment 
of RICE: Rest, Ice, Compression, Elevation of the affected site. NSAIDs and acetaminophen 
comprise of the first-line analgesic treatment for mild to moderate pain, with NSAIDs being 
theorized to decrease the inflammatory response that comes with acute injury and to alleviate the 
swelling. 13 One study examining ankle sprains showed that more than half of the pain was 
alleviated twice as much with the ibuprofen group versus a conservative treatment without 
medications group. 15 Ibuprofen and other NSAIDs have been approved for mild to moderate 
pain, along with osteoarthritis, rheumatoid arthritis, antipyretic, dysmenorrhea. Frequently, if 
pain is not controlled with acetaminophen or NSAIDs, a different modality of pain control may 
need to be added. In the past opioid medications were given for unrelieved pain but given the 
recent concern for addiction to these medications, alternative therapies for pain control are being 
studied intensively. 5  
Topical lidocaine patches are an alternative therapy that has been FDA-approved for the 
treatment of post-herpetic neuralgia. 3,6 In addition, they have also been used off-label for other 
pain conditions, such as osteoarthritis, exacerbation of chronic back pain, rib fractures, incision-
related pains, etc 1,2,7. Studies have described enhanced relief of pain via combination of 
analgesics with different mechanisms of actions. Lidocaine may provide a different mechanism 
of action by using selective inhibition of voltage-gated sodium channels, affecting the A and C 
fibers, which are main fibers used for nociceptors for pain responses.9 Due to the topical nature 
of the medications, side effect profiles are more favorable versus the systemic absorptions. 3 This 
may be advantageous especially in elderly patients who are already burdened with multiple drug 
interactions and delirium. Prior studies using the lidocaine 5% transdermal patch have shown an 
onset of action as early as 30 minutes (peak benefit 4-12 hours) with associated reduction in pain 
intensity.10 Lidocaine has also been seen to improve pain within a longer time frame post-
administration. 14 Given the lidocaine patch has recently been turned into an over-the-counter 
medication, it would be beneficial to further investigate the efficacy and possibility of its use in 
patients presenting with acute musculoskeletal pain in the Emergency Department. In this study, 
we will be performing the study using the over-the-counter formulation of lidocaine 4% patch 
(Lidocare Pain Relief Patch ™), which compared to 5% formulation, may provide less of the 


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harmful side effects with non-inferior efficacy. 12 (These side effects may include cardiac arrest, 
CNS depression, unintentional overdose, in addition to those listed in the exclusion criteria). 
Hypothesis:  
Treatment of patients who visit the emergency department with acute musculoskeletal pain with 
lidocaine patch plus an NSAID (ibuprofen in the study) will provide significant improvement in 
pain scores and decrease return visits versus treatment with only ibuprofen 
Study objectives: 
Primary objective: To determine if adding lidocaine patch to treatment with NSAIDs (ibuprofen 
in the study) will significantly improve patients’ pain scores from acute musculoskeletal injuries 
Secondary objective:  
To examine rate of return visit to the emergency department for acute musculoskeletal pain, 
given paucity of data on the subject.  
To demonstrate that lidocaine patch plus ibuprofen will decrease return visits for additional pain 
medications versus patients treated with only ibuprofen for acute musculoskeletal pain 
Study design: 
Prospective, Open-label, randomized controlled trial 
Inclusion criteria:  
Age ≥ 18 years old 
English-speaking patients 
Chief complaint of musculoskeletal pain lasting ≤7 days 
Area of greatest pain isolated to one body part 
No prior ED visits recorded on electronic medical records for the chief complaint 
Exclusion criteria: 
Age < 18 years old 
Pregnant/Breastfeeding patients 
Non-English-speaking population 
Multiple traumatic injuries or injury requiring consultation with the trauma service per hospital 
guidelines 


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Cellulitis/infection overlying the injuries 
Open wound overlying the injuries 
Pain caused by penetrating injury 
Absolute contraindications to medications, including anaphylaxis to lidocaine or NSAIDs, 
history of active GI bleeding or recent CABG surgery precluding NSAIDs, severe hepatic 
disease (hepatitis, cirrhosis in current chart or prior history or elevation in liver function tests to 
clinically significant levels in past 6 months), severe kidney disease (Cr clearance <30 mL or 
history of CKD stage 3 or worse), congestive heart failure.  
Medication contraindications (from FDA website) - concurrent use of medications below: 
● Alcuronium 
● Amphotericin B 
● Amprenavir 
● Atracurium 
● Cimetidine 
● Edrophonium 
● Enflurane 
● Fosphenytoin 
● Halothane 
● Nadolol 
● Oxprenolol 
● Pentazocine 
● Propafenone 
Patients on class I antiarrhythmics therapy (including lidocaine, procainamide, disopyramide etc) 
Injuries requiring splint/casting where patient may not be able to reach the area of greatest pain 
to apply and reapply the patch 
Prior history of chronic pain in the affected area (defined as ≥ 6 weeks of pain) 
Patients who received opioid medication in triage area or within 4 hours of initial treatment 
Inability to give pain scores due to mental status (including intoxications, hallucinations, 
psychosis, profound mental disability prohibiting patient from giving clear medical history) 
Initial numerical pain scale score of 0 (which would constitute “no pain” on the scale) 
Requiring opiate medication or muscle relaxants (Flexeril, Valium, Tizanidine, Robaxin etc) 
during the initial visit to ED at the discretion of the provider.  
Patients who received < 800 mg oral dosage of ibuprofen in triage 


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Patient Identification: 
Patients will be identified at ED triage with chief complaint related to acute (≤7 days duration) 
isolated musculoskeletal pain. 
Sample size: 
Differences in pain scores will be analyzed using a one-tail t-test. With an a priori power 
analysis, we would like to see at least a 2-point difference in pain score 11, with minimally 
clinically significant difference of 1.3 points. To achieve this, we will need at least 140 patients 
total (70 in each arm). Alpha will be set at 0.05, with power of 90%. Allowing for error or 
patient dropping out, we request that 180 people be enrolled in the study. At Vidant Medical 
Center, at least 682 patients in the month of March 2018 have come into the ED that werebilled 
as having complaint of musculoskeletal pains.  
Timeline: 
Patients will be identified at ED triage with chief complaint related to acute (≤7 days duration) of 
isolated musculoskeletal pain of one area of body. Given the volume and rate of visit through the 
Vidant Medical Center, the patient enrollment may require only a few month’s time.  
At the time of identification, inclusion and exclusion criteria will be reviewed via EHR. If unable 
to discern inclusion and exclusion criteria via this method, patient may be verbally asked about 
these criteria prior to obtaining consent. A full medical evaluation will be performed as is done 
in all ED patients prior to initiation of any study activities. 
Written consent will be obtained in triage at that time about this study, after explaining benefits 
and risks to each participant. 
Patients will be asked at the time an initial pain level with Numerical Pain Rating Scale, which 
will provide with a number from 0-10, with 0 being no pain, 10 being the worst pain possible. 
Patients will then be given one PO ibuprofen 800mg, which may be either in triage or at the 
room pending the flow of the emergency department. 
Providers will have option of two different envelopes with treatment options, which the choice of 
envelope will be randomized. One arm will be treatment with lidocaine patch (Lidocare Pain 
Relief Patch ™ (containing lidocaine 4%) patch) and ibuprofen (PO 800mg). The other arm will 
be the control arm, where only ibuprofen (PO 800mg) will be prescribed. The lidocaine patch 
will be applied to the area of maximal pain and will be replaced daily per the prescription 
(applied to the area up to 12 hours for each time then removed for 12 hours before reapplication). 
Lidocaine patches will be kept in the ED pyxis and dispensed by study team. 


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Provider will give the assigned treatment from the envelope. If the patient was randomized to the 
control arm, patient will not be receiving any further NSAIDs in the treatment rooms if initial 
dosing was at triage.  
30 min after intervention (ibuprofen only or lidocaine patch plus ibuprofen) and at discharge, 
patient will be asked to repeat the pain scale. This will be appropriate timing, since the 
ibuprofen’s onset of action is published as 25 minutes with a duration of action from 4-6 hours. 
No published time to effect data for 4% lidocaine patches can be found. It is noted to be variable 
based on vascularity of site of placement.  However, the use of 4% lidocaine topical cream is 
noted to be effective within 5-20 minutes.  In addition, measures of blood levels of lidocaine 
show that levels peak at 6-8 hours after application of a 4% patch. Because of the mechanism of 
action of lidocaine patches is to reduce the firing of pain fibers directly beneath the patch, it is 
generally considered a "fast-acting" approach to pain relief. Studies looking at 5% lidocaine 
patch has also noted some improvement to pain within 30 minutes as noted in background 
section. We believe that 30 minutes is sufficient for a patient to experience some relief of pain 
after patch application. 
Patients will be supplied for 3 days’ worth of lidocaine patches to be applied every 12 hours each 
day with removal in 12 hours, along with prescription of 3 days of ibuprofen 800mg PO every 8 
hours. Patients who are randomized into the ibuprofen only arm will get prescription for at 3 
days’ supply of ibuprofen only with the same 800mg PO every 8 hours.   
Prior to discharge, patient will be asked to repeat the pain scale, with the timing of this pain scale 
also noted at this time. 
We will review the patient’s electronic chart and see if there was a repeat visit to either Vidant 
ED or Vidant/ECU primary care provider (who are connected via Vidant’s EPIC EHR system) 
within 1 week for same chief complaint. If available, we will also review the numerical analog 
scale at the visit. 
The patient will also be contacted via phone to obtain a final pain score within 48 - 72 hours of 
discharge. At that time, a survey/questionnaire about the phone call would obtain information 
about the final pain scale score, medication usage/compliance, and any rescue prescriptions 
obtained after the initial visit. If patient’s primary care provider was unable to be viewed on the 
EHR, we would also ask about any follow-up visit that has been done or planned within 1 week 
of initial visit for the same complaint.  
It is anticipated (based on experience) that if a patient has not achieved pain relief they will 
return, or visit a primary care physician within 48 hours. The follow up time frame is based on 
the fact that the patients are provided with 72 hours of pain control. If the pain returns at that 
time, or they did not achieve relief, they are expected to seek medical care in the ED or 
elsewhere. The study will be performed as an Intention to Treat study, meaning that if follow up 


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data is not available for any patient, they will be noted as a treatment failure so that results are 
not overstated in the face of low follow-up. 
Risks and Benefits: 
Both are medications, which intrinsically carry the risks of adverse effects. However, given that 
both of the medications are available over-the-counter for pain relief without necessitating the 
evaluation of a qualified medical personnel, the risks listed below would be a very infrequent 
happening. Other risks not listed below with the manufacturer's label are listed above in the 
exclusion criteria.  
Lidocare 4% Pain Relief Patch: 
Benefit: For the temporary relief of pain.   
Risks per Manufacturer: For external use only. 
Do not use on large areas of the body or on cut, irritated skin on open wounds or sensitive skin 
for more than one week without consulting a doctor. Do not use if you are allergic to lidocaine or 
any of the inactive ingredients listed (Crospovidone, menthoxypropanediol, non-woven backing 
fabric, polyester film, non-latex rubber based adhesive, vanillyl butyl ether) 
Do not allow contact with eyes. Rash, itching or skin irritation develops. Symptoms persist for 
more than 7 days or clear up and occur again within a few days. 
Advil, Motrin, Ibuprofen: 
Benefit: For temporary relief of pain 
Risks per Manufacturer:  
Reported side effects were higher at doses of 3200 mg/day than at doses of 2400 mg or less per 
day in clinical trials of patients with rheumatoid arthritis.  
GASTROINTESTINAL: Nausea, epigastric pain, heartburn, diarrhea, abdominal distress, nausea 
and vomiting, indigestion, constipation, abdominal cramps or pain, fullness of GI tract (bloating 
and flatulence) Gastric or duodenal ulcer with bleeding and/or perforation, gastrointestinal 
hemorrhage, melena, gastritis, hepatitis, jaundice, abnormal liver function tests; pancreatitis 
CENTRAL NERVOUS SYSTEM: Dizziness, headache, nervousness, Depression, insomnia, 
confusion, emotional liability, somnolence, aseptic meningitis with fever and coma, Paresthesias, 
hallucinations, dream abnormalities, pseudotumor cerebri 
DERMATOLOGIC: Rash, (including maculopapular type), pruritus, Vesiculobullous eruptions, 
urticaria, erythema multiforme, Stevens-Johnson syndrome, alopecia, Toxic epidermal 
necrolysis, photoallergic skin reactions 


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SPECIAL SENSES: Tinnitus, Hearing loss, amblyopia (blurred and/or diminished vision, 
scotomata and/or changes in color vision), Conjunctivitis, diplopia, optic neuritis, cataracts 
HEMATOLOGIC: Neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia (sometimes 
Coombs positive), thrombocytopenia with or without purpura, eosinophilia, decreases in 
hemoglobin and hematocrit, Bleeding episodes (eg epistaxis, menorrhagia) 
METABOLIC/ENDOCRINE: Decreased appetite, Gynecomastia, hypoglycemic reaction, 
acidosis 
CARDIOVASCULAR: Edema, fluid retention (generally responds promptly to drug 
discontinuation) (see Congestive heart failure in patients with marginal cardiac function, elevated 
blood pressure, palpitations Arrhythmias (sinus tachycardia, sinus bradycardia) 
ALLERGIC: Syndrome of abdominal pain, fever, chills, nausea and vomiting; anaphylaxis; 
bronchospasm, Serum sickness, lupus erythematosus syndrome. Henoch-Schonlein 
vasculitis,angioedema 
RENAL: Acute renal failure, decreased creatinine clearance, polyuria, azotemia, cystitis, 
Hematuria, Renal papillary necrosis 
MISCELLANEOUS: Dry eyes and mouth, gingival ulcer, rhinitis 
Ethics: 
Patient may potentially benefit by receiving additional treatment for their pain. Patients who are 
randomized to the NSAIDs only arm will still be receiving standard of care for their pain. There 
is minimal harm given to patients, given that topical preparation limits systemic absorption. We 
will also screen out those who have contraindication to any of the two medications in the study. 
Written consent will be obtained. Risks and benefits will be explained at the time of consent. 
There will not be any coercion or financial incentive to enroll in the study. The staff will be 
adhering to HIPAA to maintain privacy and confidentiality. Patients will be randomized into two 
treatment arms, and physician providing care will randomize into two treatments. If the patient is 
requiring more treatment due to an adverse event, physician will freely be able to treat the patient 
based on physician’s discretion. The study team does not have financial ties with the Lidocare 
company. 
 
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