Subcutaneous Injection of Large Volumes of Tumescent Lidocaine and Epinephrine by Laypersons (TLE-RCT)

HK Surgical

Status and phase: Unknown; Phase 3; Phase 2

Conditions: Musculoskeletal Pain; Local Anesthesia; Venomous Snakebites; Painless Injection; Dermatologic Surgery; Cutaneous Pain; Regional Anesthesia

Treatments: Drug: Tumescent Lidocaine and Epinephrine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04733781

TLE-RCT

Details and patient eligibility

About

This research is intended to show that it is safe and not difficult for nearly anyone to inject at least 125ml of a dilute solution of tumescent lidocaine and epinephrine (TLE), where a TLE solution consists of lidocaine (1gm/L) and epinephrine (1mg/L) in normal saline.

Full description

The primary aim of this research is to demonstrate that of subcutaneous injection of tumescent (dilute) lidocaine and epinephrine (TLE) is safe, well tolerated, and easily performed by nearly anyone who is at least 16 years old. The primary aim will be achieved by conducting an IRB-approved double-blind, non-inferiority, randomized clinical trial (RCT).

The indications for TLE when injected into subcutaneous tissue are

• Pre-hospital treatment of a snakebite envenomation (SBE)
• Dermatologic surgical procedures totally by local anesthesia
• Pure sensory regional anesthesia for significant cutaneous and musculoskeletal pain.

The present TLE-RCT has three research Arms, which are as follows:

Injection of 125ml by a physician and self-injection of 125ml by a volunteer (Arm I): A volunteer layperson (research subject), at least 16 years of age, will first receive 125ml of TLE injected subcutaneously into the left anterior thigh by a physician. Then the subject will self-inject a second 125ml of TLE into his/her right anterior thigh.

Injection of 125ml by a physician and 125ml by another volunteer (Arm II): A volunteer layperson (primary research subject), at least 16 years of age, will first receive 125ml of TLE injected subcutaneously into the left anterior thigh by a physician. The primary research subject will then receive a second 125ml of TLE injected into his/her right anterior thigh by a second adult volunteer who is at least 16 years old and not a medical professional.

Injection of 250ml by a physician into a volunteer (Arm III) : A volunteer layperson (research subject), at least 16 years of age, will receive 250ml of TLE injected subcutaneously into the one anterior thigh by a physician.

There will be two TLE formulations, F1 and F2.

• F1 contains epinephrine 1mg/L = 1:1,000,000, or 0.25mg/250ml.
• F2 contains epinephrine 2mg/L = 1:500,000, or 0.5mg/250ml. F1 and F2 will both contain lidocaine 1gm/L = 0.1gm/100ml = 0.1% The maximum dose of dilute tumescent epinephrine in F1 and F2 is 0.25mg and 0.5mg, respectively. An EpiPen® contains 0.3mg of epinephrine. The concentration of epinephrine in an EpiPen® is 1:1000, which is 1000 and 500 times greater than the concentration of epinephrine in F1 and F2, respectively.

Individual subjects will be randomly assigned to receive either F1 or F2. The maximum dosage of tumescent lidocaine is 5mg/kg, which is clearly a safe dosage given that the risk of mild lidocaine toxicity at 28mg/kg of 0.1% TLE is 1 per 5,000,000

Enrollment: 36 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• All volunteer subjects will be healthy, mature in behavior and temperament, without mental impairment and at least 16 years of age.
• A volunteer TLE research subject must be a non-medical-professional layperson and must have signed an IRB-approved informed consent form prior to participation.
• All subjects must weigh at least 40kg = 88lb

Exclusion criteria

• Anyone who has a significant fear of needles or fear of injections
• A history of lidocaine allergy.
• A significant history of epinephrine hypersensitivity.
• History of an adverse reaction to percutaneous injections, such as fainting and lightheadedness (vasovagal reactions, near syncope).
• Significant needle phobia or anxiety.
• Vasovagal reaction associated with any medical procedures or the sight of blood.
• Uncontrolled or labile hypertension.
• Hyperthyroidism, thyroid medications.
• Recent phenylephrine (Actifed®) or pseudoephedrine use.
• Any significant cardiac arrhythmia including controlled atrial fibrillation tachycardia, mitral valve prolapse.
• Significant chronic renal impairment.
• Significant liver function abnormalities.
• History of having or having had a blood born infection with HIV, Hepatitis B, Hepatitis C.
• Evidence of active skin infection.
• Pregnant women are excluded.
• Subject has recently taken any drug(s) known to interfere with the metabolism of lidocaine such as erythromycin, clarithromycin, ketoconazole, fluconazole, sertraline (Zoloft), or ciprofloxacin.
• Subject has recently taken any drug known to interact adversely with epinephrine such as pseudoephedrine, ephedrine, or beta-blocker.
• History of radiation therapy or surgery involving the area near the proposed injection site.
• Pre-existing or concurrent infections (cutaneous, urinary, pneumonia are exclusionary).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: Quadruple Blind

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36 participants in 3 patient groups

Subcutaneous injection of 125ml by a physician and self-injection of 125ml by a volunteer (Arm I):

Active Comparator group

Description:

A volunteer layperson (research subject), at least 16 years of age, will first receive 125ml of TLE injected subcutaneously into the left anterior thigh by a physician. Then the subject will self-inject a second 125ml of TLE into his/her right anterior thigh.

Treatment:

Drug: Tumescent Lidocaine and Epinephrine

Subcutaneous injection of 125ml by a physician and 125ml by another volunteer (Arm II):

Active Comparator group

Description:

A volunteer layperson (primary research subject), at least 16 years of age, will first receive 125ml of TLE injected subcutaneously into the left anterior thigh by a physician. The primary research subject will then receive a second 125ml of TLE injected into his/her right anterior thigh by a second adult volunteer who is at least 16 years old and not a medical professional.

Treatment:

Drug: Tumescent Lidocaine and Epinephrine

Subcutaneous injection of 250ml by a physician into a volunteer (Arm III)

Active Comparator group

Description:

A volunteer layperson (research subject), at least 16 years old, will receive 250ml of TLE injected subcutaneously into the one anterior thigh by a physician.

Treatment:

Drug: Tumescent Lidocaine and Epinephrine