Subcutaneous Injection of Large Volumes of Tumescent Lidocaine and Epinephrine by Laypersons

NCT ID: NCT04733781

Last Updated: 2021-02-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2/PHASE3

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-22

Study Completion Date

2021-06-07

Brief Summary

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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.

Detailed Description

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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

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

double-blind, non-inferiority, randomized clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Participants, Care Providers, Investigator and Outcome Assessors will not know the concentration of epinephrine, either 1mg/L or 2mg/L, in the tumescent solution of lidocaine (1gm/L) to be injected subcutaneous in a participant.

Study Groups

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Subcutaneous 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.

Group Type ACTIVE_COMPARATOR

Tumescent Lidocaine and Epinephrine

Intervention Type DRUG

Subcutaneous injection of a relatively large volume (125ml to 250ml) of a relatively dilute solution of lidocaine (1gm/L) and epinephrine (1mg/L or 2mg/L).

Subcutaneous 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.

Group Type ACTIVE_COMPARATOR

Tumescent Lidocaine and Epinephrine

Intervention Type DRUG

Subcutaneous injection of a relatively large volume (125ml to 250ml) of a relatively dilute solution of lidocaine (1gm/L) and epinephrine (1mg/L or 2mg/L).

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

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.

Group Type ACTIVE_COMPARATOR

Tumescent Lidocaine and Epinephrine

Intervention Type DRUG

Subcutaneous injection of a relatively large volume (125ml to 250ml) of a relatively dilute solution of lidocaine (1gm/L) and epinephrine (1mg/L or 2mg/L).

Interventions

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Tumescent Lidocaine and Epinephrine

Subcutaneous injection of a relatively large volume (125ml to 250ml) of a relatively dilute solution of lidocaine (1gm/L) and epinephrine (1mg/L or 2mg/L).

Intervention Type DRUG

Other Intervention Names

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Tumescent Local Anesthesia

Eligibility Criteria

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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).
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Jeffrey Alan Klein, MD

INDUSTRY

Sponsor Role lead

Responsible Party

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Jeffrey Alan Klein, MD

Principal Investigator

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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HK Dermatology Care Center

San Juan Capistrano, California, United States

Site Status

Countries

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United States

Central Contacts

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Jeffrey A Klein, MD

Role: CONTACT

(949) 283-1070

Michele Horwich, RN

Role: CONTACT

(949) 248-1632

Facility Contacts

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Michele Horwich, RN

Role: primary

949-248-1632

Elena Novak, PA

Role: backup

(949) 248-1632

References

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Makdisi JR, Kim DP, Klein PA, Klein JA. Tumescent contravenom: murine model for prehospital treatment of Naja naja neurotoxic snake envenomation. Int J Dermatol. 2018 May;57(5):605-610. doi: 10.1111/ijd.13877. Epub 2018 Feb 20.

Reference Type BACKGROUND
PMID: 29460967 (View on PubMed)

Klein JA, Jeske DR. Estimated Maximal Safe Dosages of Tumescent Lidocaine. Anesth Analg. 2016 May;122(5):1350-9. doi: 10.1213/ANE.0000000000001119.

Reference Type BACKGROUND
PMID: 26895001 (View on PubMed)

Klein JA, Langman LJ. Prevention of Surgical Site Infections and Biofilms: Pharmacokinetics of Subcutaneous Cefazolin and Metronidazole in a Tumescent Lidocaine Solution. Plast Reconstr Surg Glob Open. 2017 May 30;5(5):e1351. doi: 10.1097/GOX.0000000000001351. eCollection 2017 May.

Reference Type BACKGROUND
PMID: 28607871 (View on PubMed)

Klein JA. Tumescent technique for local anesthesia improves safety in large-volume liposuction. Plast Reconstr Surg. 1993 Nov;92(6):1085-98; discussion 1099-100.

Reference Type BACKGROUND
PMID: 8234507 (View on PubMed)

Klein JA. The tumescent technique for liposuction surgery. J Am Acad Cosmetic Surg, 1987; 4:263-267.

Reference Type BACKGROUND

US Patent 10,786,483 B2. JA Klein, PA Klein, BA Klein. Tumescent Contravenom Drug Delivery (Sep 29, 2020).

Reference Type BACKGROUND

US Patent 10,493,024 B2. Klein. Tumescent infiltration drug delivery of high subcutaneous drug concentrations with prolonged local and systemic effects and minimal local or systemic toxicity (Dec 3, 2019).

Reference Type BACKGROUND

Other Identifiers

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TLE-RCT

Identifier Type: -

Identifier Source: org_study_id

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