RecruitingPhase 1

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

United States60 participantsStarted 2024-04-30

Plain-language summary

Very preterm infants are prone to numerous medical complications with lifelong impact. Amongst the most serious neurologically are white matter injury (WMI), intraventricular hemorrhage (IVH) 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, may promote neuro-repair, including the progression from early postnatal IVH to subsequent PHH. The investigators will perform a Phase I, single institution, randomized, double-blind trial for very preterm infants with IVH and WMI to define a safe combination dose of MLT and EPO. A maximum of 60 very preterm neonates with IVH and/or moderate to severe WMI 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, liquid and gut microbiome 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 neurological deficits, including the need for surgical intervention and the lifelong burden of shunted hydrocephalus.

Who can participate

Age range

12 Hours – 2 Months

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Neonatal intensive care unit (NICU) inpatients born at \>22 and \<32 weeks gestation (born after 22w-6/7 and before or on 31-6/7 week GA) * IVH or moderate/severe white matter injury within the first 21 days from birth * Infants born prior to 30 weeks GA may enroll until DOL 30. Infants born after 30 weeks may enroll until DOL 21. Treatment must be started by 33+0. * Approval of the primary neonatologist * Appropriate caregiver to provide informed consent * Is not known to meet or suspected of meeting any of the exclusion criteria (below). Exclusion Criteria: * Participation in another pharmacological intervention trial that involves multiple doses of a medication that may interact with EPO+MLT. Examples of exemptions would include single dose administration for pharmacokinetic studies of an antibiotic, a single or few doses of a new surfactant, or a single intervention to reduce pain. * Is on jet ventilator or has not been off jet ventilator for at least 72 hours * Has been diagnosed with or is suspected of having a congenital anomaly or genetic disorder associated with brain malformation or life expectancy \<40 weeks post menstrual age (PMA). These include but are not limited to TORCH infections associated with radiographic evidence of substantial brain injury, trisomy 13, coarctation of the aorta, and severe liver failure. TORCH infections not associated with radiographic evidence of brain malformation or treatment for presumed TORCH infection are …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Rate of SAE/DLT including death

Timeframe: 4 weeks after the conclusion of treatment, up to 38 weeks gestational age

Trial details

NCT IDNCT05617833

SponsorJohns Hopkins University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-09

Contact for this trial

Kathryn Lowe

443-721-4390 kathrynlowe@jhmi.edu

View on ClinicalTrials.gov More Intraventricular Hemorrhage of Prematurity trials