Botulinum Toxin Type A Injection to Prevent Keloid Recurrence

Immediate Injection of Botulinum Toxin Type A After Keloid Scar Revision to Prevent Keloid Recurrence: a Prospective, Split-scar, Double-blind, Randomized Controlled Study

The prospective, split-scar, double-blind, randomized controlled study will enroll the patients who are older than 20 years with progressive keloid lesion which is symmetric. Botulinum toxin A will be injected into half of each keloid revision wound immediately after skin closure. The scars will be assessed at 1-year follow-up with Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and the Cutometer.

Study Overview

• Status: Active, not recruiting
• Conditions: Scar Keloid
• Intervention / Treatment: Drug: Botulinum Toxin Type A Injection [Botox]; Drug: 0.9% Sodium Chloride Injection

Detailed Description

Continuous variables will be reported as the mean ± standard deviation(SD). Each aspect of the VSS score, POSAS score, and the Cutometer parameters of each scar half between the BTA and control groups will be analyzed longitudinally using the paired t test. The interrater consistency will be evaluated using the Spearman rho. All analyses will be performed with IBM SPSS Version 23.0 (IBM Corp., Redmond, Wash.). A value of p < 0.05 is considered to indicate statistical significance.

The sample size was calculated based on the results of the investigators' aforementioned study published in 2019. Thirty patients underwent keloid revision and then received radiation therapy based on our treatment protocol. The postoperative Vancouver Scar Scale score was 4.15 ± 1.74. If treatment could improve VSS score by 1, which was considered clinically significant, approximately 26 patients would have been necessary to provide a result with a real significance (using the same SD and considering the standard α error of 0.05 and a power of 0.8). Assuming a 20% non-compliance rate for follow-up evaluation, the sample size was increased to 32 patients.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Tainan, Taiwan
    • National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adult (20 years or older)
• Progressive keloid lesion that is bilaterally symmetric, mandibular area, anterior chest or suprapubic area, for example
• At least 4 cm in length
• Repeated or uncontrolled recurrence, and unendurable symptoms with poor response to conservative modalities
• Valid written informed consent provided for surgery and trial inclusion

Exclusion Criteria:

• Allergy to botulinum toxin
• Previous botulinum toxin injection at the lesion within 6 months before enrollment
• Myasthenia gravis
• Focal infection signs
• Pregnant or breastfeeding woman

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Botulinum Toxin type A injection side; The Botulinum Toxin type A will be injected into the dermal layer before skin closure in keloid excision surgery. The concentration of Botulinum Toxin type A is 100 units in 2 mL and dosage is 8 units/cm. The maximal dose is 100 units for each participant.	Drug: Botulinum Toxin Type A Injection [Botox]; After the whole surgical procedures of keloid revision are done, the participants will receive Botulinum Toxin type A (BTA) injection. The investigators split the scar into the right side and the left side. BTA and 0.9% saline, respectively, are used for the two arms of the study. Vials containing 100 units of BTA (BotoxⓇ, Allergan) are mixed with 2mL 0.9% injectable saline. The injection depth will be the intradermal layer. Injections will be performed with a 30-gauge needle and 1 mL syringe. Just before skin closure, the entire scar was treated, with sides randomized to receive treatment with either BTA or 0.9% normal saline. The dosage is 8 units / cm based on aforementioned studies. The maximal dose won't exceed 100 units.
Placebo Comparator: 0.9% saline injection side; The 0.9% saline will be injected into the dermal layer before skin closure in keloid excision surgery. The dosage is 0.16 mL/cm.	Drug: 0.9% Sodium Chloride Injection; After the whole surgical procedures of keloid revision are done, the participants will receive 0.9% saline injection. The investigators split the scar into the right side and the left side. BTA and 0.9% saline, respectively, are used for the two arms of the study. Only 0.9% saline is injected on the control side. The injection depth will be the intradermal layer. Injections will be performed with a 30-gauge needle and 1 mL syringe. Just before skin closure, the entire scar was injected, with sides randomized to receive treatment with either BTA or 0.9% normal saline. The dosage is 0.16 mL / cm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Keloid recurrence	The recurrence of keloid will be determined by clinical examination evaluated by a dermatologist.	One year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective symptoms	The subjective symptoms will be measured by the Patient Scale of the Patient and Observer Scar Assessment Scale. The Patient Scale consists six items and scores from 1 to 10 for each items. The score of 1 means much alike the normal skin and the score of 10 means worst imaginable scar.	3, 6, 9 and 12 months
Objective symptoms	The subjective symptoms will be measured by the Observer Scale of the Patient and Observer Scar Assessment Scale. The Observer Scale consists six items and scores from 1 to 10 for each items. The score of 1 means much alike the normal skin and the score of 10 means worst imaginable scar.	3, 6, 9 and 12 months
Vancouver Scar Scale	One dermatologist will evaluate the scar with the Vancouver Scar Scale. The Vancouver Scar Scale consists 4 items. The minimum score is 0, which means the scar is much alike normal skin. The maximal score is 13, which means purple, hyperpigmentation, contracture and elevated scar.	6 and 12 months
Scar firmness	The scar firmness is determined by the Cutometer parameter R0. R0 is maximum amplitude of the curve (the total elongation). The larger R0 is, the softer the scar is.	6 and 12 months

Collaborators and Investigators

• Sponsor: National Cheng-Kung University Hospital
• Collaborators: Tainan Hospital, Ministry of Health and Welfare
• Investigators: Principal Investigator: Yuan-Yu Hsueh, MD PhD, National Cheng-Kung University and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Estimated): March 20, 2024
• Study Completion (Estimated): March 20, 2024

Study Registration Dates

• First Submitted: August 30, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Radiotherapy; Keloid; Botulinum Toxin type A
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Connective Tissue Diseases; Fibrosis; Cicatrix; Collagen Diseases; Recurrence; Keloid; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: MOHW109-TDU-B-211-114003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No