Clinical trial NCT05617833: Safety of Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage
Official title: Safety of Combined Therapy With Erythropoietin and Melatonin for Very Preterm Infants With Intraventricular Hemorrhage (SCEMPI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Intraventricular Hemorrhage of Prematurity
Keywords: SCEMPI
Erythropoietin
Melatonin
preterm infants
Intraventricular Hemorrhage
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2022-11-16
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. 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)
2. sIVH within the first 21 days from birth, defined as at least unilateral grade II on head ultrasound (HUS) performed within 18 days of enrollment
3. Approval of the primary neonatologist
4. Appropriate caregiver to provide informed consent
5. Is not known to meet or suspected of meeting any of the exclusion criteria (below).

Exclusion Criteria:

1. 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.
2. Is on jet ventilator or has not been off jet ventilator for at least 72 hours
3. 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 not exclusionary.
4. Is within 3 days of starting treatment for a severe clinical condition which is potentially associated with a life expectancy \<3 days. These include but are not limited to disseminated intravascular coagulation (DIC)/severe hematologic crisis, severe sepsis, Hypoxic-ischemic encephalopathy (HIE), severe brain injury
5. Other clinical conditions including:

   Hydrops fetalis Hypertension for age requiring sustained medication Polycythemia (hematocrit \>65%)
6. No caregiver to provide consent

The clinical condition of potential candidates will be monitored throughout the eligibility period to ensure the participant's continued candidacy for participating in the trial.

Primary outcomes:
measure: Rate of SAE/DLT including death
timeFrame: 4 weeks after the conclusion of treatment, up to 38 weeks gestational age
Secondary outcomes:
measure: Efficacy of EPO plus MLT as assessed by rate of preterm birth related co-morbidities
timeFrame: 4 weeks after the conclusion of treatment, up to 38 weeks gestational age
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Shenandoah Robinson, MD
role: STUDY_CHAIR
References: