Safety of Clonidine in Infants With Hypoxic Ischemic Encephalopathy During Therapeutic Hypothermia

• Status: Completed
• Trial end date: 2015-04-14
• Target enrollment: 0
• Participant gender: All

Summary

This research is being done to find out the safety of the investigational study drug, Clonidine Hydrochloride ( CLON). , in infants who are undergoing whole body cooling for the treatment of hypoxic ischemic encephalopathy (HIE). The only known and effective treatment for HIE is therapeutic hypothermia or whole body cooling for72 hours. During the cooling process, babies get agitated, shiver and are uncomfortable. To treat these side effects morphine is frequently used. CLON is very effective in decreasing shivering in adults and children. Furthermore, in some preclinical studies, clonidine has been shown to be neuroprotective (safe for the brain in models of brain injury)..This is a Phase I-II to determine if low dose CLON will reduce the incidence of shivering and whether it has short term cardiovascular safety. In this Phase I-II study, the investigators will determine the (i) the maximum tolerated dose of CLON during cooling for HIE, (ii) the effects of CLON on heart rate, blood pressure, core body temperature and cerebral autoregulation (ability to maintain constant blood flow to the brain) and (iii) association between blood levels and changes in the above parameters. In this study the investigators hope to find ways to improve sedation, shivering and agitation in newborn infants with HIE on the cooling protocol. Our ultimate goal is determine the potential neuro-protective properties of clonidine in newborn babies with HIE.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Estelle B. Gauda, MD; Johns Hopkins University
• Collaborators: University of Maryland; University of Maryland, College Park
• Treatments: Clonidine

Criteria

Inclusion Criteria:

• Infants ≥35 0/7 weeks gestation with the diagnosis of HIE who are being treated with therapeutic hypothermia, who have indwelling arterial lines

• Informed parental consent

Exclusion Criteria:

• Infants who are considered moribund and the clinical team is considering withdrawal of support

• Infants who need > 20 µg/kg/min of dopamine or the addition of epinephrine or dobutamine to maintain a mean arterial pressure (MAP) ≥ 45 mmHg, or milrinone for cardiovascular support

• Baseline heart rate (HR) <80 bpm during hypothermia

• Infants suspected of major chromosomal anomalies, except trisomy 21

• Infants with major cardiovascular anomalies

• Infants with severe persistent pulmonary hypertension of the newborn who are enrolled and who then need Extracorporal Membrane Oxygenation (ECMO) will be withdrawn from the study