Efficacy of Intralesional Bleomycin Alone and in Combination With Dexamethasone in Infantile Haemangiomas
Condition: Comparison of Efficacy of Sclerotherapy in Infantile Hemangioma
MeSH terms: Hemangioma; Hemangioma, Capillary; Port-Wine Stain
Study type: Interventional

Summary: 
      Objective:

      This study is intended to compare the outcome of intralesional bleomycin with dexamethasone
      versus the bleomycin alone in infantile haemangioma.

      Materials and Methods:

      This RCT was performed after the ethical approval at the pediatric surgery department of
      KEMU/Mayo hospital Lahore. 114 patients were enrolled in two groups A and B. Both groups
      contained 57 patients each. Group A was administered intralesional bleomycin with
      dexamethasone and group B was given intralesional bleomycin alone with a space of 4 weeks.
      Selection of patients was made according to inclusions and exclusion criteria.
    

Detailed description: 
      Introduction:

      Infantile haemangioma (IH) is a common tumor found in children. The history of this tumor
      consists of an early phase of growth followed by slow resolution over a period of three to
      seven years but can extend up to 12 years. Therapeutic intervention is usually not required
      in infantile hemangiomas due to spontaneous regression. In about 10 to 15% of cases IH
      located in the perineal, airway or periocular areas, or hemangiomas associated with
      complications of ulceration, intervention is necessary. Another reason for intervention in
      these hemangiomas is the probability of scar formation with complete or incomplete
      spontaneous involution. Currently available treatment options for IH range from topical,
      intralesional, systemic and laser therapies to surgery based on the stage and presentation of
      the tumor. The choice of treatment must be carefully selected after comparing the merits and
      risks of each modality through a patient-specific approach.

      OPERATIONAL DEFINITION:

      Infantile Haemangioma: is a benign vascular proliferative disorder which has an early period
      of proliferation and then regresses spontaneously. They are found during the infancy and are
      considered medically benign lesions.

      Efficacy: The desired effect obtained after giving a treatment is termed as efficacy.
      Efficacy of the treatment was measured in terms of reduction of the size of haemangioma which
      in turn was assessed by measuring length, width, height and volume every month to a period of
      one year. The decrease in size was graded on 5 point scale where 1= < 50% reduction, 2=
      50-75%, 3= 75-90%, 4= >90% but < 100% and 5= 100%[17]. The complete flattening of haemangioma
      was considered as resolution of the lesion and at least the reduction in size of grade 2
      results was labelled as the treatment being efficacious.

      Intralesional Injection: After aseptic measures the injection was administered using a 26
      gauge needle by directly injecting into the haemangioma in 4 different directions (the lesion
      was divided into 4 imaginary quadrants by drawing to perpendicular lines) through the single
      puncture point. Sterile gauze was used for pressure until the bleeding stopped.

      Dosage: The intralesional dose of bleomycin was 1 mg/kg/dose but for haemangiomas on neck and
      face it was used as 0.5 mg/kg/dose and similarly intralesional dexamethasone was given as
      0.8-1.6 mg/kg/dose. Both the drugs were administered intralesionally every 4 weeks. Every
      patient was checked for sensitivity to the drugs.

      Treatment Response: The response of the treatment was evaluated by measuring Length, Width,
      Height and Volume. The length, width and height was measured using a vernier calliper in
      centimeters before administering the first injection and then after every 4 weeks following
      each injection.

      Hypothesis:

      The intralesional bleomycin combined with dexamethasone is more efficacious than
      intralesional bleomycin alone in infantile haemangioma.

      Material and Methods:

      Study Design: It was be a Randomized Controlled Trial.

      Study Setting: The study was conducted in Pediatric surgery department, KEMU/Mayo Hospital
      Lahore.

      Duration Of The Study: 1 year after the approval of the synopsis. Sampling Technique:
      Probability simple random sampling. Sample Size: Sample size of 114 patients ( 57 patients in
      each group ) is estimated by using 95% confidence level, 10% absolute precision with expected
      percentage of intralesional bleomycin combined with dexamethasone as 100%[15] and
      intralesional bleomycin alone as 82%[10] .

      n = Z1-α/2 [ P1 (1- P1) + P2 (1- P2) ] d2 Where n = sample size P1 = population proportion I
      = 100% P2 = population proportion II = 82% Z1-α/2 = confidence level 95% = 1.96 d = absolute
      precision 10%

      Sample Selection:

      Inclusion Criteria:

        1. Patients with haemangiomas presenting to pediatric surgery department KEMU/Mayo hospital
           Lahore with size equal or more than 1 cm.

        2. Patients </= 12 years and above 1 month of age.

      Exclusion Criteria:

        1. Patients who had undergone any surgical procedure for haemangiomas proved from the
           history.

        2. Patients with chronic respiratory conditions confirmed by history, symptoms and physical
           examination.

        3. The diagnosed case of pulmonary fibrosis.

        4. Patients sensitive to bleomycin proved upon giving a test dose.

      DATA COLLECTION PROCEDURE:

      Permission was taken from the ethical review board. Patients were selected as per inclusion
      and exclusion criteria. Written informed consent was taken from parents/guardians regarding
      inclusion in study and sharing of data after counseling about the procedure, drug effects and
      follow up. A randomized control trial study was conducted on patients of haemangiomas of
      pediatric age group coming to pediatric surgery ward, KEMU/Mayo hospital, Lahore. Patients
      were randomized in two study groups A and B. The Lottery method was used for allocation of
      patients where the patient was given allocated treatment regimen after opening the sealed
      envelope. Each group contained 57 of patients. Patients in the group A were given
      intralesional bleomycin combined with dexamethasone and in the group B intralesional
      bleomycin alone after taking aseptic and antiseptic measures. The intralesional dose of
      bleomycin was 1 mg/kg/dose but for haemangiomas on neck and face it was used as 0.5
      mg/kg/dose and similarly intralesional dexamethasone was given as 0.8-1.6 mg/kg/dose. The
      Length, Width, Height and volume of haemangioma was measured in centimeters using a vernier
      calliper. The decrease in size was graded from 1-5 where 1=<50% decrease, 2=50-75%, 3=75-90%,
      4=>90% but <100% and 5= 100% resolution. The data collection sheet included patent's age,
      sex, length, width, height, volume, site of haemangioma, dose of bleomycin, dexamethasone,
      clinical response being efficacious or non-efficacious as per operational definition and time
      taken to resolve for each patient.

      DATA ANALYSIS PROCEDURE:

      Data was entered and processed by using SPSS-26. Quantitative variable like age, length,
      width, height, volume, grades of improvement and time for resolution was presented as mean+SD
      . Qualitative variables like site of haemangioma, gender and efficacy was described using
      frequencies and percentages. Comparison of two groups "intralesional bleomycin alone" and
      "intralesional bleomycin combined with dexamethasone" was done by applying independent sample
      t-test. P-value if <0.05 was taken as significant.
    

Intervention name(s): Comparison of intralesional injection of bleomycin alone and combined with injection dexamethasone
Intervention type(s): Drug
Intervention description(s): already described
Intervention MeSH terms: Dexamethasone; Bleomycin
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized control trial study was conducted on patients of haemangiomas of pediatric age group coming to pediatric surgery ward, KEMU/Mayo hospital, Lahore. Patients were randomized in two study groups A and B. The Lottery method was used for allocation of patients where the patient was given allocated treatment regimen after opening the sealed envelope. Each group contained 57 of patients. Patients in the group A were given intralesional bleomycin combined with dexamethasone and in the group B intralesional bleomycin alone after taking aseptic and antiseptic measures. T
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: infantile hemangioma; Bleomycin; Sclerotherapy; Dexamethasone; Combined sclerotherapy