Clinical trial NCT04288700: Evaluation of the Efficacy of Captopril Versus Propranolol and Timolol as a Treatment of Infantile Capillary Hemangioma
Official title: Evaluation of the Efficacy of Captopril Versus Propranolol and Timolol as a Treatment of Infantile Capillary Hemangioma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Infantile Hemangioma
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2020-02-28
Enrollment: 100
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Assessment of serum levels of Vascular endothelial growth factor
timeFrame: 6 months
measure: Assessment of serum levels of CD 133
timeFrame: 6 months
measure: Assessment of the size of the lesion.
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Vascular malformation clinic of Pediatric Surgery department of Ain Shams University.
Study officials:
affiliation: Future University in Egypt
name: Rana Atta, BSc
role: PRINCIPAL_INVESTIGATOR
References: