Intra-lesional ACE Inhibitor for Treatment of Hypertrophic Scars

NCT05259137 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: 24816
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Hypertrophic scarring is a difficult and debilitating condition where one develops excessive scarring after full thickness injury to the skin. This is very common in full thickness burn injury. Currently, there is no reliable treatment of these scars. One of the more effective treatments available is serial intralesional injection of a steroid. Angiotensin II is an active peptide in the body that results in vasoconstriction of the blood vessels when activated. Medications used today like angiotensin II receptor blocks and angiotensin converting enzyme inhibitors work to prevent the activation of angiotensin II and are mainly used to help control blood pressure. Previous studies in rat models have shown that angiotensin II receptor blockers can effectively reduce scar hypertrophy. In this study, the investigators will conduct a randomized control trial with a paired split-scar design. One arm receiving the standard therapy of serial intra-lesional injections of triamcinolone acetonide (TAC) and the second arm receiving an ACE-inhibitor. The outcome will be measured using the Patient and Observer Scar Assessment Scale (POSAS), a validated assessment tool.

Conditions

Hypertrophic Scar

Keywords

Keloid; Scar; Hypertrophy; ACE inhibitor; Angiotensin converting enzyme inhibitor; Enalapril; Hypertrophic

Outcome Measures

Primary Outcomes (1)

• Change in Patient and Observer Scar Assessment Scale (POSAS)

  The POSAS patient scale uses patient-reported measurements of symptoms (pain and itchiness) and signs (colour, stiffness, thickness, irregularity) to quantify the degree of the scar. Similarly, the POSAS observer scale uses measurements of scar vascularity, pigmentation, thickness, relief, pliability, and surface area in order to quantify development of scar tissue. For the observer, the maximum score is 50 and the minimum score is 5. A higher score indicates a worse outcome. For the patient, the maximum score is 60 and the minimum score is 6. A higher score indicates a worse outcome.

  Outcomes will be measured at 0, 6-, 12-, and 52 weeks

Study Arms (2)

Intra-lesional triamcinolone acetonide

NO INTERVENTION

This arm will will be our control. They will receive current standard of care of a single intra-lesional injection of 1 mL of 10mg/mL triamcinolone acetonide at 0 weeks, 6 weeks, and 12 weeks.

Intra-lesional triamcinolone acetonide + enalaprilat

EXPERIMENTAL

This will be our intervention experiment. They will receive a single intra-lesional injection of 1.0 mL of 1.25 mg/mL of enalaprilat at 0 weeks, 6 weeks, and 12 weeks.

Drug: Intralesional enalaprilat injection

Interventions

Intralesional enalaprilat injection DRUG

1.0 mL of 1.25 mg/mL enalaprilat

Also known as: Enalaprilat

Intra-lesional triamcinolone acetonide + enalaprilat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with scar tissue demonstrating features of hypertrophic scarring (e.g., raised, red tissue, contractures, extends beyond the boundary of the original wound)

You may not qualify if:

• scar does not demonstrate any distinguishing features of hypertrophic scar;
• self-reported as pregnant and/or breastfeeding;
• documented hepatic, heart, or renal dysfunction;
• patients with known Cushing's disease or glaucoma;
• documented history of angioedema;
• patients with diabetes;
• patients being treated with any anti-hypertensive medications
• patients under 18 years of age

Sponsors & Collaborators

• Nova Scotia Health Authority: lead

Related Publications (14)

• Barone N, Safran T, Vorstenbosch J, Davison PG, Cugno S, Murphy AM. Current Advances in Hypertrophic Scar and Keloid Management. Semin Plast Surg. 2021 Aug;35(3):145-152. doi: 10.1055/s-0041-1731461. Epub 2021 Jul 15.

  PMID: 34526861 BACKGROUND

• Kaschina E, Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press. 2003;12(2):70-88. doi: 10.1080/08037050310001057.

  PMID: 12797627 BACKGROUND

• Griffith BH. The treatment of keloids with triamcinolone acetonide. Plast Reconstr Surg. 1966 Sep;38(3):202-8. doi: 10.1097/00006534-196609000-00004. No abstract available.

  PMID: 5919603 BACKGROUND

• Al-Attar A, Mess S, Thomassen JM, Kauffman CL, Davison SP. Keloid pathogenesis and treatment. Plast Reconstr Surg. 2006 Jan;117(1):286-300. doi: 10.1097/01.prs.0000195073.73580.46.

  PMID: 16404281 BACKGROUND

• Niessen FB, Spauwen PH, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg. 1999 Oct;104(5):1435-58. doi: 10.1097/00006534-199910000-00031. No abstract available.

  PMID: 10513931 BACKGROUND

• Chatterjee K, De Marco T. Systemic and coronary haemodynamics and pharmacodynamics of enalapril and enalaprilat in congestive heart failure. Drugs. 1990;39 Suppl 4:29-40; discussion 41-2. doi: 10.2165/00003495-199000394-00007.

  PMID: 2162294 BACKGROUND

• Franchignoni F, Giordano A, Vercelli S, Bravini E, Stissi V, Ferriero G. Rasch Analysis of the Patient and Observer Scar Assessment Scale in Linear Scars: Suggestions for a Patient and Observer Scar Assessment Scale v2.1. Plast Reconstr Surg. 2019 Dec;144(6):1073e-1079e. doi: 10.1097/PRS.0000000000006265.

  PMID: 31764669 BACKGROUND

• Danielsen PL, Rea SM, Wood FM, Fear MW, Viola HM, Hool LC, Gankande TU, Alghamdi M, Stevenson AW, Manzur M, Wallace HJ. Verapamil is Less Effective than Triamcinolone for Prevention of Keloid Scar Recurrence After Excision in a Randomized Controlled Trial. Acta Derm Venereol. 2016 Aug 23;96(6):774-8. doi: 10.2340/00015555-2384.

  PMID: 26911400 BACKGROUND

• Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, van Zuijlen PP. The patient and observer scar assessment scale: a reliable and feasible tool for scar evaluation. Plast Reconstr Surg. 2004 Jun;113(7):1960-5; discussion 1966-7. doi: 10.1097/01.prs.0000122207.28773.56.

  PMID: 15253184 RESULT

• Juckett G, Hartman-Adams H. Management of keloids and hypertrophic scars. Am Fam Physician. 2009 Aug 1;80(3):253-60.

  PMID: 19621835 RESULT

• Kawano Y, Yoshida K, Matsuoka H, Omae T. Chronic effects of central and systemic administration of losartan on blood pressure and baroreceptor reflex in spontaneously hypertensive rats. Am J Hypertens. 1994 Jun;7(6):536-42. doi: 10.1093/ajh/7.6.536.

  PMID: 7917152 RESULT

• Morelli Coppola M, Salzillo R, Segreto F, Persichetti P. Triamcinolone acetonide intralesional injection for the treatment of keloid scars: patient selection and perspectives. Clin Cosmet Investig Dermatol. 2018 Jul 24;11:387-396. doi: 10.2147/CCID.S133672. eCollection 2018.

  PMID: 30087573 RESULT

• Murphy A, LeVatte T, Boudreau C, Midgen C, Gratzer P, Marshall J, Bezuhly M. Angiotensin II Type I Receptor Blockade Is Associated with Decreased Cutaneous Scar Formation in a Rat Model. Plast Reconstr Surg. 2019 Nov;144(5):803e-813e. doi: 10.1097/PRS.0000000000006173.

  PMID: 31385893 RESULT

• van de Kar AL, Corion LU, Smeulders MJ, Draaijers LJ, van der Horst CM, van Zuijlen PP. Reliable and feasible evaluation of linear scars by the Patient and Observer Scar Assessment Scale. Plast Reconstr Surg. 2005 Aug;116(2):514-22. doi: 10.1097/01.prs.0000172982.43599.d6.

  PMID: 16079683 RESULT

MeSH Terms

Conditions

Cicatrix, Hypertrophic; Keloid; Cicatrix; Hypertrophy

Interventions

Enalaprilat

Condition Hierarchy (Ancestors)

Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Collagen Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Enalapril; Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Bezuhly, MD, MSc

  Dalhousie University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2022
• First Posted: February 28, 2022
• Study Start: August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share