Effect of Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03110341|
Recruitment Status : Recruiting
First Posted : April 12, 2017
Last Update Posted : October 2, 2017
|Condition or disease||Intervention/treatment||Phase|
|Premature Infants Intracranial Hemorrhages Periventricular Leukomalacia Cerebral Palsy||Drug: Erythropoietin Drug: Normal saline||Phase 3|
HYPOTHESIS Early administration of human erythropoietin (EPO) in preterm infants reduces perinatal injury to the brain and improves neurodevelopmental outcome at 24 months corrected age.
PRIMARY OBJECTIVE To determine whether cerebral outcome is improved if infants born between 28 0/7 and 34 6/7 gestational weeks at birth receive erythropoietin in high dose in the first two weeks after birth.
Biomarkers of encephalopathy of prematurity assessed on magnetic resonance imaging (MRI) at term equivalent age.
RATIONALE Erythropoietin (EPO) was first recognized for its hematopoietic properties; recombinant human EPO (rhEPO) has been used to treat a number of anemic states, including early and late anemia of prematurity, and it has been found to be safe and to reduce the need for blood transfusions. EPO produced in the central nervous system7 is upregulated after insult and plays a role in neuroprotection. Experimental studies have reported that rhEPO possesses neuroprotective properties in different neonatal brain injury animal models, and clinical studies have shown that rhEPO treatment reduces brain injury and the incidence of neurological disabilities in infants.8,14-17 In addition, improved neurodevelopmental outcomes have been observed in preterm infants with anemia after rhEPO treatment. The neuroprotective effect of rhEPO was suggested to be through acting against apoptosis, inflammation, and neurotoxicity and by acting as an antioxidant in protecting white matter from injury and in promoting neural regeneration, injury repair, and normal development.
STUDY DESIGN Randomized, double-masked, placebo-controlled multicenter clinical trial. Research plan 400 infants will be randomized during the first three hours of life to receive EPO (5250 U/kg body weight) or placebo intravenously, the first dose(750U/kg) will be injected within 24h after birth, subsequent injection will be given each other day for 2 weeks. Standardized evaluation including cerebral sonography at day 1, 7 and 28 will determine the presence or absence of complications. Cerebral volume and white matter volume will be assessed at 40 postmenstrual weeks with MRI (only if available).
Experienced examiners will assess developmental function at 6 and 12 months corrected age using the reliable and validly revised Bayley Scales III of Infant Development and determine the presence or absence of impairment of motor function (cerebral palsy) and neurosensory function (blindness or deafness).
Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 1 years corrected age.
Second outcome assess the effect of early administration of rh Epo on white matter development in preterm infants using Tract-based spatial statistics (TBSS ). White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||400 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||Effect of Early Application of Recombinant Human Erythropoietin in Premature Infants on White Matter Lesions and Neurodevelopmental Outcome|
|Actual Study Start Date :||April 10, 2017|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||June 2019|
Erythropoietin is administered 750U/kg intravenously every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections regardless of gestational age), starting with the first dose within 72 hours after birth. A single dose consisted of 750U EPO per kg of birth weight dissolved in 3mL/kg normal saline was administered intravenously during a period of 5 minutes.
Drug: Normal saline
placebo (Normal saline 3 ml/kg birth weight) was injected within 72h after birth, subsequent injection was given every other day for 2 weeks.
Other Name: NaCl 0.9%
Placebo Comparator: Normal saline
Normal saline is administered 3ml/kg intravenously every other day for 2 weeks, starting with the first dose within 72 hours after birth. Similarly, the placebo dose consisted of 3mL of normal saline per kilogram birth weight was administered intravenously during a period of 5 minutes.
rhEPO 750U/kg was injected within 72h after birth, subsequent injection was given every other day for 2 weeks (a cumulative dose of 5,250U/kg over the course of 7 separate intravenous injections.
Other Name: Epoetin Beta
- Neurodevelopmental outcome [ Time Frame: corrected age of 18 months ]To evaluate neurodevelopmental function via Bayley Scales of Infant Development, second edition (BSID-II) at 18 months corrected age and gain incidence of MDI<70(Severe) or MDI<85(Moderate).
- TBSS（Tract-based spatial statistics） [ Time Frame: corrected age of 40 weeks ]White matter disease of the preterm infant, was semiquantitatively assessed from MRI at term-equivalent age based on an established scoring method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03110341
|Contact: Xihui Zhou, Doctoremail@example.com|
|First Affiliated Hospital of Xian JiaotongUniversity||Recruiting|
|Xi'an, Shaanxi, China, 710061|
|Contact: Xihui Zhou, Doctor +8618991232230 firstname.lastname@example.org|
|Principal Investigator:||Xihui Zhou, Doctor||First Affiliated Hospital of Xian JiaotongUniversity|