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

February 3, 2021 updated by: Jeffrey Alan Klein, MD

Subcutaneous Injection of Large Volumes of Tumescent Lidocaine and Epinephrine (TLE) by Laypersons: a Double-blind, Non-inferiority, Randomized Clinical Trial

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.

Study Overview

Detailed 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

Study Type

Interventional

Enrollment (Anticipated)

36

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jeffrey A Klein, MD
  • Phone Number: (949) 283-1070
  • Email: jeff@kleinmd.com

Study Contact Backup

Study Locations

    • California
      • San Juan Capistrano, California, United States, 92675
        • HK Dermatology Care Center
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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.
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).
Other Names:
  • Tumescent Local Anesthesia
Active Comparator: 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.
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).
Other Names:
  • Tumescent Local Anesthesia
Active Comparator: 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.
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).
Other Names:
  • Tumescent Local Anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: up to 24 hours
the incidence of any clinically significant adverse event associated with TLE injection, such as pain at injection site, vasovagal event, tachycardia, infection
up to 24 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Numerical Pain Scale (NPS)
Time Frame: immediately after intervention
Numerical Pain Scale (NPS) score following each injection, where the range of he scale is 0 to 10, and where 0= "no pain" and 10="worst imaginable pain"
immediately after intervention
Pulse Rate
Time Frame: up to 30 minutes after intervention
Measure difference between pulse rates before and after subcutaneous injection of 250ml of TLE.
up to 30 minutes after intervention
Blood Pressure Changes
Time Frame: up to 30 minutes after intervention
Measure the differences between systolic and diastolic blood pressures before and after subcutaneous injection of 250ml of TLE.
up to 30 minutes after intervention
EKG rhythm changes
Time Frame: up to 30 minutes after intervention
EKG rhythm strips will be recorded before and after 250ml of TLE and any significant changes will be documented. Prior to the initial subcutaneous injection of the TLE solution, the EKG rhythm will be noted and recorded. For example, if the "pre-TLE" rhythm is "Normal Sinus Rhythm (NSR)" this observation will be recorded. After the subcutaneous TLE injection, a second EKG rhythm will be recorded. The analysis of the these two EKG rhythm strips will provide a dichotomous outcome variable: "no clinically significant EKG change" or "potentially significant EKG change." If there is a significant EKG rhythm strip change, then any relevant clinical details or observations will be recorded.
up to 30 minutes after intervention
Human-Factors Associated with subcutaneous injection of a largfe volume of a TLE solution.
Time Frame: during the intervention
Human-factor, or user interface difficulties encountered during the TLE injection process will be observed and a narrative of the observations will be recorded. The TLE-RCT is intended to demonstrate that any layperson can give a 125ml subcutaneous injection of a TLE in a manner that is safe and effective and essentially non-inferior to a similar injection administered by a physician. We will observe and record an apparent difficulties experience by the layperson when giving the injection. We will ask questions of the layperson to determine if the "instructions for use" are sufficient, and if not, we will record their suggestions for improvement.
during the intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 22, 2021

Primary Completion (Anticipated)

June 1, 2021

Study Completion (Anticipated)

June 7, 2021

Study Registration Dates

First Submitted

January 24, 2021

First Submitted That Met QC Criteria

February 1, 2021

First Posted (Actual)

February 2, 2021

Study Record Updates

Last Update Posted (Actual)

February 8, 2021

Last Update Submitted That Met QC Criteria

February 3, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Other researcher, who wish to replicate our RCT-TLE trial will be provided with de-identified data upon request.

IPD Sharing Time Frame

Data will be available at the time that the data is first presented in a public forum.

IPD Sharing Access Criteria

All information will be uploaded to www.tumescent.com

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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