Comparative Study to Evaluate the Effectiveness of Atenolol and Propranolol in the Treatment of Infantile Hemangiomas
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Mean difference in number of patients achieving complete clinical clearance of lesion (PGA Score of 5) in the two groups
Study Overview
Brief Summary
Through this study, the investigators shall compare the effectiveness of atenolol with propranolol in the treatment of IH. In addition, the investigators shall try to elucidate the mechanism of action of beta blockers by assessing their action on triggers such as hypoxia. The study design will be a parallel group comparative study wherein patients of IH will be randomized into two groups. One group will receive propranolol and the other atenolol for a maximum period of 9 months. The patients will then be followed up regularly for regression of the IH based on Physician global assessment, hemangioma activity score(HAS), serial photography and lesional ultrasonography. Any side effects encountered during the treatment period will also be noted. Also serial measurements of hypoxia inducible factor 1 alpha(HIF-1α) will be made to ascertain the mechanism of action of the drugs.
Detailed Description
AIMS AND OBJECTIVES:
- To compare the effectiveness and safety of oral atenolol versus oral propranolol in the treatment of infantile hemangiomas.
- To elucidate the mechanism of action of atenolol and propranolol in the treatment of infantile hemangiomas.
STUDY DESIGN MATERIALS AND METHODS:
This investigator-initiated, prospective, observer blinded, parallel group comparative study on the effect of oral medication in infantile cutaneous hemangiomas is being conducted in the Department of Dermatology, Venereology and Leprology, and Pediatric Surgery, Post Graduate Institute of Medical Education and Research, after getting approval from the institutional Research and Ethics Committee.
Sample size: As this is a pilot study, an arbitrary sample size of 60 (30 in each group) was decided to be kept.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- — to 12 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Children diagnosed with problematic infantile hemangiomas
- •Potentially disfiguring infantile hemangiomas at any site.
- •Functionally threatening infantile hemangiomas near the eyes, nose, natural orifices, limbs, genitalia.
- •Ulcerated infantile hemangiomas.
- •Segmental infantile hemangiomas.
- •Uncomplicated progressive infantile hemangiomas with unpredictable future course.
- •Age group: less than 1 year of age.
- •Multiple hemangiomas
Exclusion Criteria
- •Infants with heart disease, cardiac arrhythmias
- •Broncho -obstructive disease.
- •Premature infants with corrected age less than 40 weeks.
- •Known hypoglycemia
- •Diabetes mellitus
- •Hypertension
- •Hypotension
- •Liver failure
- •Visceral hemangiomas
- •PHACES syndrome
Arms & Interventions
Group A- Propranolol
Oral propranolol 1mg/kg/day as crushed tablets, in two divided doses, increased to 2mg/kg/day in two divided doses after 24 hours if tolerated well. Treatment will be stopped at complete clinical clearance of lesion (defined arbitrarily as >90% reduction in the size of Infantile Hemangioma as assessed by Physician Global Assessment) or after 9 months of treatment (primary end point) whichever is earlier.
Intervention: oral propranolol (Drug)
Group B- Atenolol
Oral atenolol 0.5mg/kg as a single dose, increased to 1mg/kg as a single dose after 24 hours if tolerated well. Treatment will be stopped at complete clinical clearance of lesion (defined arbitrarily as >90% reduction in the size of Infantile Hemangioma as assessed by Physician Global Assessment) or after 9 months of treatment (primary end point) whichever is earlier.
Intervention: oral atenolol (Drug)
Outcomes
Primary Outcomes
Mean difference in number of patients achieving complete clinical clearance of lesion (PGA Score of 5) in the two groups
Time Frame: 9 months
Physician Global Assessment Responses to therapy (change of thickness, color, and area) will be recorded on each follow up.The therapeutic responses will be evaluated on a score of 1-5 as follows by an independent dermatologist who will not know the therapies: Score 5: \>90% improvement or complete clinical involution Score 4: excellent improvement(75-90% decrease) Score 3: good improvement(50-74% decrease) Score 2: minimal improvement( 25-49% decrease) Score 1: poor improvement(1-24% decrease) Score 0: failure (no difference or regrowth)
Mean difference in Hemangioma Activity Score in the two groups
Time Frame: 9 months
Hemangioma Activity score Patient name: Age: Location of infantile hemangioma: ("Bright red edge" should only be scored when the HOI is not totally "bright red" Skin colored after activity". Do not score in deep HOI (deep swelling) unless the HOI has changed into it after activity) Date Deep swelling: tense HOI(6) 'neutral' HOI at t=0 or less than 50% reduction at follow up(4) \>=50% reduction at follow up (2) No more swelling at follow up (0) Bright red/ shining red HOI(5) OR bright red edge(4) Matt red/reddish purple HOI/ matt red edge(3) Blue HOI or Blue shining through in deep HOI(2) Grey HOI(1) Skin colored after activity(0) Total score: Number of items scored Preliminary HAS= total score/number of items scored Ulcer=\<1cm2 (+0.5) Ulcer 1-25cm2(+1) Ulcer \>=25cm2(+2) HAS= preliminary HAS + ulcer score
Frequency of adverse effects (minor and serious) in the two groups
Time Frame: 9 months
Mean difference in number of days required to achieve complete clinical clearance of lesion (PGA Score of 5) in the two groups
Time Frame: 9 months
Secondary Outcomes
- Mean difference in HIF-1α levels before and after treatment in Group A and Group B(9 months)
Investigators
Raihan Ashraf
Junior Resident, Department of Dermatology
Post Graduate Institute of Medical Education and Research, Chandigarh