Bleomycin Jet Injections in Keloids

Intralesional Bleomycin Treatment of Keloids Using an Electronic Pneumatic Jet Injector: a Double-blind Randomized, Placebo-controlled Trial With Split-lesion Design

This is a single center, double-blind (patient and investigator), randomized, placebo-controlled study with a split-lesion design, in which selected keloids will receive three consecutive treatments of a) bleomycin and b) placebo (saline (NaCl 0,9%)), administered with an electronic pneumatic jet injector.

Study Overview

• Status: Active, not recruiting
• Conditions: Keloid
• Intervention / Treatment: Drug: Bleomycin; Drug: Normal saline

Detailed Description

This is a single center, double-blind (patient and investigator), randomized, placebo-controlled study with a split-lesion design.All study procedures will be performed at the Department of Dermatology, Erasmus MC Medical Center in patients referred for scar treatment to our outpatient clinic.

Clinical photos will be obtained after signing the informed consent form by patient and investigator. Study visits and clinical assessments will be scheduled at baseline, 4 weeks, 8 weeks, and 12 weeks. Measurements include clinical photography, scar volume measured by 3D-camera, POSAS questionnaire, laser speckle contrast imaging to visualize keloid scar vascularization, measurement of residue formation on the skin, and a treatment related questionnaire. The keloid will be divided into two treatment areas, and randomly assigned to three consecutive treatments of: a) bleomycin and b) placebo (saline (NaCl 0,9%)), administered with an electronic pneumatic jet injector.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Eramsus Medical Centre, Dermatology department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has provided written informed consent;
2. Subject is ≥ 18 years of age at time of screening;
3. Subject has at least one keloid scar of ≥ 4 cm in length, or two separate keloids with a length of ≥2cm, with a minimum > 1.0 cm apart in the same anatomical region.
4. Subject is willing to fill in questionnaires and take photos using an e-diary application on their phone.

Exclusion Criteria:

1. Known hypersensitivity to any component of the test materials;
2. Pregnant or breast-feeding women (pregnancy test prior to treatment);
3. Previous bleomycin treatment of the keloid within the last 12 weeks prior to screening.
4. Non-response to previous bleomycin treatments of the keloid.
5. Any medical or psychiatric condition which, in the investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Bleomycin jet-injections; This study consists of a split-lesion design in which the keloid scar will receive three consecutive treatments with an interval of 4 weeks of: 1) bleomycin and 2) placebo (NaCl 0,9%), administered with an electronic pneumatic jet injector. A single injection of 100 μL will be given per 1 cm2, with a maximum of 20 injections per treatment. The maximum dosage of bleomycin per treatment will be 2 mL, corresponding to 2 USP-E (units) of bleomycin. The maximum cumulative dosage of bleomycin will be 6 USP-E in this study.	Drug: Bleomycin; Intralesional bleomycin treatment administered with an electronic pneumatic jet injector
Placebo Comparator: Placebo jet-injections; This study consists of a split-lesion design in which the keloid scar will receive three consecutive treatments with an interval of 4 weeks of: 1) bleomycin and 2) placebo (NaCl 0,9%), administered with an electronic pneumatic jet injector. A single injection of 100 μL will be given per 1 cm2, with a maximum of 20 injections per treatment. The maximum dosage of normal saline per treatment will be 2 mL.	Drug: Normal saline; Intralesional placebo treatment of normal saline administered with an electronic pneumatic jet injector

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume reduction	Volume reduction of scar tissue in mm^3.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical efficacy using Patient and Observer Scar Assessment Scale (POSAS)	Evaluation of clinical efficacy using Patient and Observer Scar Assessment Scale. The POSAS consists of six items (vascularization, pigmentation, thickness, relief, pliability and surface). Each item will be scored on a scale from 1 (normal skin) to 10 (worst scar). The scores of these six items result in the 'POSAS total score', also on a scale from 1 (normal skin) to 10 (worst scar).	12 weeks
Vascular perfusion	Evaluation of changes in keloid vascular perfusion using Laser Speckle Contrast Imaging.	12 weeks
Residue formation on skin	Evaluation of the average residue formation on skin in percentage of the injection volume.	30 minutes
Procedure related pain	Evaluation of the procedure related pain using a numerical rating scale (NRS) score. This scale ranges from 0-10 points, with higher scores indicating greater pain intensity.	30 minutes
Local skin reactions	Evaluation of the local skin reactions using self-taken photos in an e-diary.	12 weeks
Treatment satisfaction	Evaluation of treatment satisfaction using a 5-point Likert scale. This scale ranges from -2 to 2 points, with higher scores indicating higher satisfaction.	12 weeks
Incidence of Treatment-Emergent Adverse events [Safety and Tolerability].	Evaluation of safety and tolerability by evaluating all adverse events. Patients will daily be asked to take pictures of the treated lesion(s), and to report any adverse event via an digital e-diary application.	12 weeks

Collaborators and Investigators

• Sponsor: Erasmus Medical Center
• Collaborators: Centre for Human Drug Research, Netherlands
• Investigators: Principal Investigator: Martijn van Doorn, MD, PhD, Erasmus MC

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Anticipated): November 18, 2022
• Study Completion (Anticipated): March 30, 2023

Study Registration Dates

• First Submitted: October 5, 2020
• First Submitted That Met QC Criteria: October 5, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Actual): November 9, 2022
• Last Update Submitted That Met QC Criteria: November 7, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Dermatology; Keloid; Bleomycin; Jet-injection
• Additional Relevant MeSH Terms: Pathologic Processes; Connective Tissue Diseases; Fibrosis; Cicatrix; Collagen Diseases; Keloid; Antineoplastic Agents; Antibiotics, Antineoplastic; Bleomycin
• Other Study ID Numbers: BLEO JET

Plan for Individual participant data (IPD)

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

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