Effect of Recombinant Human EPO on the Postoperative Neurologic Outcome in Pediatric Moyamoya Patients

Study Overview
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Brief Summary
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This study evaluates the effect of recombinant human erythropoietin (rHuEPO) on the neovascularization of pediatric moyamoya disease patients. rHuEPO will be administrated during perioperative period of the first revascularization surgery. Primary outcome (Incidence of Good postoperative MCA territory revascularization by cerebral angiography) will be evaluated after 3-6 month of revascularization surgery.

Official Title
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The Effect of Recombinant Human Erythropoietin on the Postoperative Neurologic Outcome in Pediatric Moyamoya Disease Patients - A Double Blind Randomized Controlled Trial

Conditions
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Pediatrics, Moyamoya Disease, Cerebrovascular Disorders

Intervention / Treatment
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* Drug: erythropoietin
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric Moyamoya patients scheduled for the first revascularization surgery Exclusion Criteria: Hypersensitivity or contraindication to rHuEPO History of Unstable hypertension, Hypertensive encephalopathy, Thrombosis Primary intracerebral hemorrhage (ICH), Subarachnoid hemorrhage (SAH), Arterio-venous malformation (AVM), Cerebral aneurysm, or cerebral neoplasm History of seizure Hemoglobin >16 mg/dl Prolonged PT (PT > 15.5 seconds, PT INR > 1.2) or Prolonged aPTT (> 40 seconds) Thrombocytopenia (platelet count < 100,000/microL), Thrombocytosis (platelet count > 400,000/microL), Neutropenia (absolute neutrophil count (ANC) < 1500/microL) Abnormal kidney function (Creatinine> 2.0 mg/dl, History of dialysis) Abnormal hepatic function (aspartate transaminase> 80 unit/L, alanine aminotransferase> 80 unit/L)

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rHuEPO<br>recombinant human erythropoietin 500 U/kg IVS x 3 times Preoperative day (12-24 hour before surgery) During surgery Postoperative day (12-24 hour after surgery) | Drug: erythropoietin<br>* Recombinant human erythropoietin (500 U/kg IVS x 3 times) is administrated to increase the neovascularization after revascularization surgery.<br>* Other names: rHuEPO;|
| Placebo Comparator: Control<br>Normal saline 50mL x 3 times Preoperative day (12-24 hour before surgery) During surgery Postoperative day (12-24 hour after surgery) | Drug: Normal saline<br>* Control group, no intervention.<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| postoperative <12 month Angiogenesis | Incidence of Good postoperative MCA territory revascularization by cerebral angiography or MRI (3 grade: good, fair, poor) | <12 month after revascularization operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short-term postoperative outcome: Incidence and number of the postoperative transient ischemic attack (TIA) within 1 week | Incidence and number of the postoperative transient ischemic attack (TIA) within 1 week (yes or no) | up to 1 week | 
| Short-term postoperative outcome: Adverse neurologic event | seizure, increased intracranial pressure, cerebral infarct, hematoma, reoperation (yes or no) | within the 1st postoperative hospital stay, up to 1 year | 
| Short-term postoperative outcome: Other postoperative complications | e.g. Circulatory failure/arrest, Respiratory failure/arrest, Infection (yes or no) | within the 1st postoperative hospital stay, up to 1 year | 
| Short-term postoperative outcome: ICU stay (days) | ICU stay (discharge criteria: Stable V/S + Consciousness) | within the 1st postoperative hospital stay, up to 1 year | 
| Short-term postoperative outcome: Total hospital stay (days) | Total hospital stay (discharge criteria: Stable V/S + no progressive Sx) | within the 1st postoperative hospital stay, up to 1 year | 
| Effect of rHuEPO on perioperative erythropoiesis: Total intraoperative and perioperative transfusion requirements (mL/kg) | Total intraoperative and perioperative transfusion requirements (mL/kg) | within the 1st postoperative hospital stay, up to 1 year | 
| Effect of rHuEPO on perioperative erythropoiesis: Perioperative Hemoglobin, Hematocrit, serum EPO level | Perioperative Hemoglobin, Hematocrit, serum EPO level | within the 1st postoperative hospital stay, up to 1 year | 
| Effect of rHuEPO on perioperative erythropoiesis: GFR, BUN, Creatinine | GFR, BUN, Creatinine level | within the 1st postoperative hospital stay, up to 1 year | 
| Postoperative <12 month neurologic outcome: Clinical outcomes (4 grade): Excellent, Good, Fair, Poor | Clinical outcomes (4 grade): Excellent, Good, Fair, Poor | Outpatient clinical visit, Usually Postoperative 3 6 month, up to 1 year | 
| Postoperative <12 month neurologic outcome: Brain Perfusion MRI (2 grade): Favorable, Unfavorable | Brain Perfusion MRI (2 grade): Favorable, Unfavorable | Outpatient clinical visit, Usually Postoperative 3 6 month, up to 1 year | 
| Long-term neurologic outcome: Clinical outcomes (4 grade): Excellent, Good, Fair, Poor | Clinical outcomes (4 grade): Excellent, Good, Fair, Poor | Outpatient clinical visit, Usually Postoperative 12 18 month, up to 2 years | 
| Long-term neurologic outcome: Brain MRI/A or Brain perfusion MRI | Brain MRI/A or Brain perfusion MRI (2 grade): Favorable, Unfavorable | Outpatient clinical visit, Usually Postoperative 12 18 month, up to 2 years | 
| Long-term neurologic outcome: Cognitive function assessed by Korean Wechsler Intelligence Scale for Children-Ⅳ (K-WISC-Ⅳ) | Cognitive function assessed by Korean Wechsler Intelligence Scale for Children-Ⅳ (K-WISC-Ⅳ, has 4 domaines: Verbal Comprehension Index, Perceptual Reasoning Index, Working Memory Index, Processing Speed Index > final score is calculated from T-score) | Outpatient clinical visit, Usually Postoperative 12 18 month, up to 2 years | 
| Preoperative Cerebral angiography: Suzuki grade, Bilateral involvement | Cerebral angiography: Suzuki grade(1-6), Bilateral involvement (yes/no) | Before up to 1 year | 
| Preoperative Brain MRI/A or Brain Perfusion MRI | Brain MRI/A or Brain Perfusion MRI (2 grade): Favorable, Unfavorable | If the preoperative w/u is not completed before recruitment, up to 1 week | 
| Preoperative Hemoglobin, Hematocrit, serum EPO level | Preoperative Hemoglobin, Hematocrit, serum EPO level | If the preoperative w/u is not completed before recruitment, up to 1 week | 
| Preoperative information: Homozygous RNF213 | Homozygous RNF213 | If the preoperative w/u is not completed before recruitment, up to 1 week |