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

Cerebrovascular Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03882060
• Other study ID #: H-1812-165-999
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 8, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: November 2023
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Cerebrovascular Disorders
• Moyamoya Disease
• Pediatrics

Intervention

Drug:
• erythropoietin
Recombinant human erythropoietin (500 U/kg IVS x 3 times) is administrated to increase the neovascularization after revascularization surgery.
• Normal saline
Control group, no intervention.

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Seoul National University Hospital

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (11)

Aljaaly HA, Aldekhayel SA, Diaz-Abele J, Karunanayka M, Gilardino MS. Effect of Erythropoietin on Transfusion Requirements for Craniosynostosis Surgery in Children. J Craniofac Surg. 2017 Jul;28(5):1315-1319. doi: 10.1097/SCS.0000000000003717. — View Citation

Bang OY, Fujimura M, Kim SK. The Pathophysiology of Moyamoya Disease: An Update. J Stroke. 2016 Jan;18(1):12-20. doi: 10.5853/jos.2015.01760. Epub 2016 Jan 29. — View Citation

Heeschen C, Aicher A, Lehmann R, Fichtlscherer S, Vasa M, Urbich C, Mildner-Rihm C, Martin H, Zeiher AM, Dimmeler S. Erythropoietin is a potent physiologic stimulus for endothelial progenitor cell mobilization. Blood. 2003 Aug 15;102(4):1340-6. doi: 10.1182/blood-2003-01-0223. Epub 2003 Apr 17. Erratum In: Blood. 2004 Jun 15;103(12):4388. — View Citation

Hong JM, Lee SJ, Lee JS, Choi MH, Lee SE, Choi JW, Lim YC. Feasibility of Multiple Burr Hole With Erythropoietin in Acute Moyamoya Patients. Stroke. 2018 May;49(5):1290-1295. doi: 10.1161/STROKEAHA.117.020566. Epub 2018 Apr 6. — View Citation

Kim JH, Jung JH, Phi JH, Kang HS, Kim JE, Chae JH, Kim SJ, Kim YH, Kim YY, Cho BK, Wang KC, Kim SK. Decreased level and defective function of circulating endothelial progenitor cells in children with moyamoya disease. J Neurosci Res. 2010 Feb 15;88(3):510-8. doi: 10.1002/jnr.22228. — View Citation

Kim SK, Cho BK, Phi JH, Lee JY, Chae JH, Kim KJ, Hwang YS, Kim IO, Lee DS, Lee J, Wang KC. Pediatric moyamoya disease: An analysis of 410 consecutive cases. Ann Neurol. 2010 Jul;68(1):92-101. doi: 10.1002/ana.21981. — View Citation

Kim T, Oh CW, Bang JS, Kim JE, Cho WS. Moyamoya Disease: Treatment and Outcomes. J Stroke. 2016 Jan;18(1):21-30. doi: 10.5853/jos.2015.01739. Epub 2016 Jan 29. — View Citation

Kimakova P, Solar P, Solarova Z, Komel R, Debeljak N. Erythropoietin and Its Angiogenic Activity. Int J Mol Sci. 2017 Jul 13;18(7):1519. doi: 10.3390/ijms18071519. — View Citation

Malla RR, Asimi R, Teli MA, Shaheen F, Bhat MA. Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. J Perinatol. 2017 May;37(5):596-601. doi: 10.1038/jp.2017.17. Epub 2017 Mar 9. — View Citation

Wu YW, Mathur AM, Chang T, McKinstry RC, Mulkey SB, Mayock DE, Van Meurs KP, Rogers EE, Gonzalez FF, Comstock BA, Juul SE, Msall ME, Bonifacio SL, Glass HC, Massaro AN, Dong L, Tan KW, Heagerty PJ, Ballard RA. High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics. 2016 Jun;137(6):e20160191. doi: 10.1542/peds.2016-0191. Epub 2016 May 2. — View Citation

Yoo YC, Shim JK, Kim JC, Jo YY, Lee JH, Kwak YL. Effect of single recombinant human erythropoietin injection on transfusion requirements in preoperatively anemic patients undergoing valvular heart surgery. Anesthesiology. 2011 Nov;115(5):929-37. doi: 10.1097/ALN.0b013e318232004b. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Effect of rHuEPO on perioperative erythropoiesis: GFR, BUN, Creatinine	GFR, BUN, Creatinine level	within the 1st postoperative hospital stay, up to 1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Long-term neurologic outcome: Cognitive function assessed by Korean Wechsler Intelligence Scale for Children-? (K-WISC-?)	Cognitive function assessed by Korean Wechsler Intelligence Scale for Children-? (K-WISC-?, 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
Secondary	Preoperative Cerebral angiography: Suzuki grade, Bilateral involvement	Cerebral angiography: Suzuki grade(1-6), Bilateral involvement (yes/no)	Before up to 1 year
Secondary	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
Secondary	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
Secondary	Preoperative information: Homozygous RNF213	Homozygous RNF213	If the preoperative w/u is not completed before recruitment, up to 1 week