Safety of Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage

Intraventricular Hemorrhage of Prematurity Clinical Trial

— SCEMPI  

Official title:

Safety of Combined Therapy With Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage (SCEMPI)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05617833
• Other study ID #: IRB00301237
• Secondary ID: R01HD104673-01A1
• Status: Recruiting
• Phase: Phase 1
• Start date: April 15, 2024
• Est. completion date: September 30, 2027

Study information

• Verified date: April 2024
• Source: Johns Hopkins University
• Contact: Jessica Wollett
• Phone: 667-306-8141
• Email: jwollet1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious are severe intraventricular hemorrhage (sIVH) and the subsequent progression to posthemorrhagic hydrocephalus (PHH). Currently, the only treatment for PHH is surgery, most commonly with shunts that are prone to malfunction across the lifespan. Preclinical data show that melatonin (MLT) and erythropoietin (EPO), when administered in a sustained dosing regimen, can prevent the hallmarks of progression from early postnatal sIVH to subsequent PHH. The investigators will perform a Phase I, single institution, randomized, double-blind trial for very preterm infants with sIVH to define a safe combination dose of MLT and EPO. A maximum of 60 very preterm neonates with sIVH will be enrolled, treated through 33w6/7d, and followed to 37w6/7d. Neonates will be randomized 3:1 between MLT+EPO and placebo, with all receiving standard of care. The primary endpoint is a composite serious adverse event (SAE)/dose limiting toxicity (DLT). The investigators hypothesize that the MLT+EPO SAE/DLT rate will not be higher than the placebo rate. Secondary outcomes will be rate of co-morbidities of preterm birth. Exploratory data, collected to guide design of future clinical trials for efficacy, will include serial neuro-imaging metrics acquired from clinical images, serial neonatal neurodevelopmental examinations, serum and urine MLT and EPO levels, and liquid biomarkers. Successful implementation of this initial safety trial will provide essential data to guide the next stage of clinical trials to test if sustained MLT+EPO treatment can reduce the need for surgical intervention, and avoid the lifelong burden of shunted hydrocephalus.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: September 30, 2027
• Est. primary completion date: September 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Hours to 2 Months

Eligibility

Inclusion Criteria:

• Neonatal Intensive Care Unit (NICU) inpatients born at >22 and <32 wks gestation (born after 22w6d and before or on 31-6/7 wk GA)

• sIVH within the first 21 days from birth, defined as at least unilateral grade III on head ultrasound performed within the past 5 days

• expected to survive at least 3 days

• absence of a congenital anomaly of metabolic or genetic disorder with expected survival less than term equivalent

• approval of the primary neonatologist

• arterial or venous access

• appropriate caregiver to provide informed consent

Exclusion Criteria:

• life expectancy <3 days for any reason

• severe congenital anomaly or genetic disorder with life expectancy <40 w post-menstrual age (PMA)

• liver failure

• severe hematologic crisis such as disseminated intravascular coagulation

• hydrops fetalis

• polycythemia (hematocrit < 65%)

• hypertension for age requiring medication

• clinical concern or diagnosis of toxoplasmosis, cytomegalovirus, rubella or syphilis infection

• no appropriate person available or willing to provide informed consent

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intraventricular Hemorrhage of Prematurity

Intervention

Combination Product:
• MLT+EPO
Melatonin component will be a single daily dose of 30 mg/kg enteral administered in the evening. EPO component is a two-stage regimen with high dose EPO (1000 U/kg/dose q 48 hrs ± 2hr IV) for 10 doses followed by maintenance dose EPO (400 U/kg/dose q Monday, Wednesday, Friday IV/SC) to 33-6/7wk. Maintenance EPO dosing will begin on the day closest to completing the high dose series.

Other:
• Placebo
Placebo enteral and IV

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of SAE/DLT including death	to test the hypothesis that rate of Serious Adverse Events (SAE)/dose limiting toxicity (DLT) with a cocktail of MLT and EPO in very preterm infants with severe intraventricular hemorrhage (sIVH) will have similar rate of SAE/DLT in subjects treated with placebo	4 weeks after the conclusion of treatment, up to 38 weeks gestational age
Secondary	Efficacy of EPO plus MLT as assessed by rate of preterm birth related co-morbidities	Determine whether treatment with EPO plus MLT alters the rate of preterm birth related co-morbidities compared to concurrent placebo controls.	4 weeks after the conclusion of treatment, up to 38 weeks gestational age