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

Conditions

• Intraventricular Hemorrhage of Prematurity

Eligibility Criteria

Sex

ALL

Age

12 Hours - 2 Months

Healthy Volunteers

Not accepted

Interventions

• MLT+EPO — COMBINATION_PRODUCT
  Melatonin component will be a daily dose of 30 mg/kg enteral administered in the evening in a split dose given at cares/feedings. EPO component is a two-stage regimen with high dose EPO (1000 U/kg/dose q 48 hrs ± 2hr subcutaneously or intravenously) for 10 doses followed by maintenance dose EPO (400 U/kg/dose q Monday, Wednesday, Friday subcutaneously or intravenously) to 33-6/7wk. Maintenance EPO dosing will begin on the day closest to completing the high dose series.
• Placebo — OTHER
  Placebo enteral and IV

Study Details

Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious are significant 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.

Key Dates

Start date

Apr 30, 2024

Status verified

Jun 2026

Primary completion

Sep 30, 2027

Completion

Sep 30, 2027

Study Design

Enrollment

60 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: MLT+EPO
  Melatonin 3 mg/mL oral syringe enterally every evening. Dose will be divided in half and administered at evening cares. High dose epoetin alfa epbx recombinant (1000 units/kg) syringe subcutaneously or intravenously every 48 hours for 10 doses. Low dose epoetin alfa-epbx recombinant (400 units/kg) subcutaneously or intravenously three times weekly on Monday, Wednesday, and Friday until age 33-6/7wk.
• Placebo Comparator: Placebo
  Placebo oral syringe enterally every evening. Placebo syringe IV every 48 hours for 10 doses. Placebo subcutaneously or intravenously three times weekly on Monday, Wednesday, and Friday until age 33-6/7wk.

Primary Outcome Measure

Rate of SAE/DLT including death [ Time Frame: 4 weeks after the conclusion of treatment, up to 38 weeks gestational age ]

Central Contacts

• Kathryn Lowe
  443-721-4390
  [email protected]
• Jessica Wollett
  667-306-8141
  [email protected]

Locations (2)

Find similar trials in St. Petersburg, FL

Related Studies

• Light Therapy Device for Neonatal Intraventricular Hemorrhage Grade 3 and 4
  Recruiting · Rutgers, The State University of New Jersey · Newark, New Jersey