The general mechanisms in infants’ and adults’ bodies are different. Yet standard treatment for infant epilepsy uses the same drugs used for adults. The drug most commonly used to treat infant seizures is phenobarbital. Yet the efficacy rate is less than 50%. Even combined with phenytoin, the second most-used medication, only 62% of infants respond to the combination treatment.
Neurologist Janet Soul has been looking for a solution to control neonatal seizures since 2009. She began testing with bumetanide, which has been used as a diuretic in infants. The drug has been on the market for over 40 years but only now is it being tested as a potential anti seizure medication for infants. At the time she began testing, Soul had been treating 426 infants with seizures, of which 64% didn’t respond to the regular antiseizure medication. Seventeen percent died in the neonatal ICU. She decided to test a drug that has been known to be safe for infants, bumetanide. Soul’s initial trial run with 43 newborns was a success. Now Boston Hospital is preparing to lead a larger phase 2 trial with higher doses of the drug. The trial will be carried out through the Network of Excellence in Neuroscience Clinical Trials (NeuroNEXT).
Dr. Soul’s study
Dr. Soul’s trial was funded by the NIH at Boston Children’s, Massachusetts General Hospital, Brigham and Women’s Hospital, and Tufts Children’s Hospital. All of the 43 infants that took part of the study suffered from refractory (drug-resistant) seizures. Twenty-seven of the infants received IV bumetanide in addition to phenobarbital therapy. Participants received 0.1 mg/kg, 0.2 mg/kg, or 0.3 mg/kg of bumetanide in a dose-escalation design. The remaining 16 newborns received phenobarbital treatment along with a placebo. All of the infants were EEG monitored for four hours after receiving treatment. Among the experimental group, 26 (96%) infants survived. However, two remained hearing impaired. Within the control group, 13 (81%) newborns survived and none were hearing impaired.
This study reiterates the idea that what works for adults may not work in children, particularly newborns. Further research is needed to expand on these promising results since Bumetanide has been studied in neonates in the past and published with negative findings and an increased risk of hearing loss.