Evaluating the Effect of Isotretinoin in Regulatory T-cell Function in Adverse Cutaneous Drug Eruptions (ACDEs): A Pilot Study

The purpose of this study is to determine whether isotretinoin is helpful in treating patients with an adverse cutaneous drug eruption known as toxic epidermal necrolysis (TEN).

Study Overview

• Status: Withdrawn
• Conditions: Toxic Epidermal Necrolysis
• Intervention / Treatment: Other: Placebo; Drug: Isotretinoin

Detailed Description

Toxic epidermal necrolysis (TEN) is a potentially life-threatening skin disorder characterized by widespread redness, blistering and peeling of skin.

Currently, supportive care in the standard treatment for patients with TEN. Isotretinoin, an FDA-approved medication commonly used for treating severe acne induces differentiation of certain inflammatory cells and thus may potentially be helpful in treating patients with TEN.

This is a randomized, placebo-controlled, double-blind, pilot study comparing the efficacy and safety of isotretinoin versus placebo in treating subjects with toxic epidermal necrolysis (TEN).

Approximately 40 subjects who satisfy all inclusion and exclusion criteria will be randomly assigned in a 1:1 ratio to either isotretinoin or placebo which they will take for up to 14 days. The end of the study is defined as the time the subject is discharged from the hospital. Participants will primarily be assessed for percent body surface affected (BSA) and number of days of hospitalization.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Arturo Saavedra, MD, PhD; Phone Number: 617-726-5066; Email: harvardskinstudies@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 69 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 - 69 years of age
2. Has biopsy-proven toxic epidermal necrolysis (TEN)

3. If female, should not be of childbearing potential defined as:

   • Have not had menstrual periods for 12 months in a row (menopause) OR
   • Had bilateral oophorectomy or total hysterectomy OR
   • Have a ovarian disorder that would make pregnancy not possible

Exclusion Criteria:

1. Unknown HIV status and unwilling to undergo HIV testing
2. Women of childbearing potential
3. Pregnancy
4. Breastfeeding
5. Fasting serum triglyceride levels >25% of upper limit of normal
6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase levels >2× upper limit of normal (ULN)
7. Known allergy to isotretinoin
8. History of suicidal attempt, psychosis, major depression or other serious mood disorders
9. Currently taking vitamin A supplements, tetracyclines, phenytoin, corticosteroids, IVIg or St. John's Wort
10. Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (for example, compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments
11. Participation in an interventional study within the past 30 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Isotretinoin; Isotretinoin will be given at the following dosage: Dosing will be as listed on the table below. Weight in Kg Total Daily Dose 40-49 Kg 40mg 50-89 Kg 80mg 90-150 Kg 120mg	Drug: Isotretinoin
Placebo Comparator: Placebo; Subjects will be given placebo capsules twice a day.	Other: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days of hospitalization	Number of days patient will be hospitalized.	up to 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of body surface affected (BSA)	Maximum body surface affected with TEN.	up to 14 days

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Arturo Saavedra, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Estimated): June 1, 2020
• Study Completion (Estimated): June 1, 2020

Study Registration Dates

• First Submitted: June 6, 2016
• First Submitted That Met QC Criteria: June 8, 2016
• First Posted (Estimated): June 9, 2016

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: TEN
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Immune System Diseases; Stomatognathic Diseases; Mouth Diseases; Hypersensitivity; Erythema; Skin Diseases, Vesiculobullous; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Hypersensitivity, Delayed; Stomatitis; Erythema Multiforme; Drug Hypersensitivity; Stevens-Johnson Syndrome; Drug Eruptions; Dermatologic Agents; Isotretinoin
• Other Study ID Numbers: 2016P000845

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO