Evaluation of the Efficacy of Captopril Versus Propranolol and Timolol as a Treatment of Infantile Capillary Hemangioma

NCT ID: NCT04288700

Last Updated: 2020-02-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2021-10-01

Brief Summary

Is to compare and evaluate the efficacy of oral captopril with oral propranolol, intralesional propranolol injection, and topical Timolol in the treatment of infantile hemangioma and their effect on vascular endothelial growth factor and CD 133.

Detailed Description

Infantile hemangiomas are the most common benign tumor of infancy, affecting up to 10% of the pediatric population with a higher incidence in female (3:1), preterm infants, and Caucasian population. The molecular mechanisms underlying pathogenesis remain incompletely understood, but the clinical course follows a stereotyped pattern: a phase of early vascular proliferation over the first year of life followed by a gradual phase (1 to7 years in duration) of spontaneous involution and replacement of vascular channels by fibro-fatty tissue. Despite their benign nature,in certain cases IHs can cause severe morbidities and therefore sometimes require medical intervention.

Vascular endothelial growth factor A is the predominant growth factor associated with endothelial proliferation, migration, and survival. Vascular endothelial growth factor, being a potent inducer of vascular permeability, is known to cause edema and lead to formation of hemangiomas in high concentrations along with CD133 is a transmembrane glycoprotein which represents a cell surface marker for hemangioma-derived stem cells (HemSCs). CD133-positive HemSCs can still be differentiated into hemangiomas, suggesting that CD133-positive HemSCs have continuous ability to form hemangiomas. Targeted elimination of CD133-positive HemSCs could fundamentally inhibit the proliferation of hemangioma.

Aim of the study is to compare and evaluate the efficacy of oral captopril with oral propranolol, intralesional propranolol injection, and topical Timolol in the treatment of infantile hemangioma and their effect on vascular endothelial growth factor and CD 133.

Methodology : Open label Randomized Controlled trail will be carried out at Vascular malformation clinic of Pediatric Surgery department of Ain Shams University ,Patients of the study will be randomly allocated equally into 4 groups (A, B, C, D), 25 patients each.

• Group A: Subjected to oral propranolol therapy at a dose of 2 mg/kg/d in three divided doses.
• Group B: Oral Captopril will be administered as a test dose of 0.1 mg kg orally with pulse rate and blood pressure monitored at 0.5, 1 and 2 h and at each follow up. If the test dose is tolerated, captopril administration will start at 0.15 mg/ kg) per dose 8-hourly. Pulse rate and blood pressure will be monitored 4-hourly and doses will be withheld if hypotension is documented. After 24 h, the dose will be increased to 0.3 mg/ kg) per dose 8-hourly.
• Group C: Subjected to intralesional propranolol injection 1 mg/mL. The volume of injected drug depends on the size of the lesion (0.2 mL will be injected per cm of lesion diameter), with a maximum volume of 1 mL for a lesion of 5 cm diameter
• Group D: Subjected to topical Timolol maleate 0.5% eye drops on the surface of the lesions three times daily and gentamycin ointment will be applied around the lesions to prevent the timolol from leaking.

Following up: Venous blood samples will be withdrawn from all study participants at study entry and after 6 months of treatment for assessment of serum levels of VEGF and CD 133 by ELISA technique along with the size of the lesion.

Conditions

Infantile Hemangioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A

Group Type: ACTIVE_COMPARATOR

oral propranolol

Intervention Type: DRUG

oral propranolol therapy at a dose of 1 mg/kg/d (Inderal 20 mg/5 mL) in three divided doses. If the child will tolerate the treatment with no side effects, therapy will continue in an outpatient clinic. Blood glucose level will be also measured in a periodic manner during therapy. The dose will be increased gradually to 2 mg/kg/d in three divided doses if there will be no adverse effects from the initial therapy.

Group B

Group Type: ACTIVE_COMPARATOR

Oral Captopril

Intervention Type: DRUG

A test dose of 0.1 mg kg) will be administered orally with pulse rate and blood pressure monitored at 0.5, 1 and 2 h and at each follow up. If the test dose is tolerated, captopril administration will start at 0.15 mg kg) per dose 8-hourly. Pulse rate and blood pressure will be monitored 4-hourly and doses will be withheld if hypotension is documented. After 24 h, the dose will be increased to 0.3 mg kg) per dose 8-hourly .

Group C

Group Type: ACTIVE_COMPARATOR

intralesional propranolol injection

Intervention Type: DRUG

intralesional propranolol injection 1 mg/mL

Group D

Group Type: ACTIVE_COMPARATOR

topical Timolol maleate 0.5% eye drops

Intervention Type: DRUG

To be Applied on the surface of the lesions three times daily

Interventions

oral propranolol

oral propranolol therapy at a dose of 1 mg/kg/d (Inderal 20 mg/5 mL) in three divided doses. If the child will tolerate the treatment with no side effects, therapy will continue in an outpatient clinic. Blood glucose level will be also measured in a periodic manner during therapy. The dose will be increased gradually to 2 mg/kg/d in three divided doses if there will be no adverse effects from the initial therapy.

Intervention Type: DRUG

Oral Captopril

A test dose of 0.1 mg kg) will be administered orally with pulse rate and blood pressure monitored at 0.5, 1 and 2 h and at each follow up. If the test dose is tolerated, captopril administration will start at 0.15 mg kg) per dose 8-hourly. Pulse rate and blood pressure will be monitored 4-hourly and doses will be withheld if hypotension is documented. After 24 h, the dose will be increased to 0.3 mg kg) per dose 8-hourly .

Intervention Type: DRUG

intralesional propranolol injection

intralesional propranolol injection 1 mg/mL

Intervention Type: DRUG

topical Timolol maleate 0.5% eye drops

To be Applied on the surface of the lesions three times daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Pediatric patients younger than 12 years and older than 2 months of age with infantile hemangioma

Exclusion Criteria

• Patient with ulcerated or infected hemangioma.
• Patient younger than 2 months and older than 12 years of age.
• Patients with multiple hemangiomas.
• Any Patient with cardiovascular problems, bronchial asthma, diabetes mellitus, bilateral renal stenosis, Electrolyte disturbance, or renal impairment was excluded.
• Patients with abnormal electrocardiogram, or echocardiogram should be excluded.
• Patients who have had previous treatment for hemangioma.

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Rana Mohamed El-Sayed Ibrahim Atta

Teaching Assistant, Pharmacy Practice and Clinical Pharmacy Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rana Atta, BSc

Role: PRINCIPAL_INVESTIGATOR

Future University in Egypt

Locations

Vascular malformation clinic of Pediatric Surgery department of Ain Shams University.

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Atta

Role: CONTACT

Phone: 01007276664

Email: rana.mohamed.108@outlook.com

Ayman El-Baghdadi, MD

Role: CONTACT

Phone: 01001223773

Email: aymanalbaghdady@yahoo.com

Facility Contacts

Ayman El-Boghdadi, MD

Role: primary

Other Identifiers

257

Identifier Type: -

Identifier Source: org_study_id