Who can participate?
Infants hospitalized at Boston Children’s Hospital who have HIE. Patients who have not opted out will be enrolled in the research trial by the treating team without informed consent at the time of NICU admission.
How to participate
Hydrogen therapy needs to be initiated as early as possible. Upon NICU admission with the diagnosis of HIE, patients will be randomly assigned to be treated with 2% hydrogen or not and continuing for 72 hours. Hydrogen treatment is the experimental therapy undergoing investigation.
We will be measuring how feasible it is to administer hydrogen in this complex environment, any adverse events that may be related to hydrogen administration (we did not find any in our research study, nor have they been described by others), and will begin to examine for any signs that hydrogen decreases brain, kidney, or other organ damage using lab tests.
We estimate that the entire research study will take 3 years to complete.
What other therapies are available to treat the injury that occurs after HIE?
The majority of care in HIE is focused on supporting the patient as the body recovers from this injury. This includes hypothermia for three days, as well as making sure that enough oxygen is delivered to the brain and other organs (including making sure that the blood pressure and oxygen levels are normal). All of these therapies will be given to all patients in this research study, and hydrogen will be a therapy added to these treatments – one that is designed to actively treat the injury itself.
Safety
Participating in this research trial will not affect any other care that your child would receive. No standard therapy will be denied by participating in the research trial. Your child’s safety will continue to be the top priority.
Exception From Informed Consent and the HIE Study
In most cases, informed consent will not be feasible. Births complicated by HIE are are emotionally and mentally traumatic for families. These deliveries are completely unexpected for families, who have in most cases experienced a healthy and uneventful pregnancy. A sudden catastrophic event occurs at the time of birth, requiring emergent cardiorespiratory support of the infant, including placement of a breathing tube and often CPR to restore blood circulation. Immediately after the child is stabilized, they are brought urgently to the NICU for ongoing care.
Hydrogen is most effective when started immediately. Whenever possible, study personnel will try to obtain your consent, or at least provide you an opportunity to object before the drug is started. In every case, after your child is enrolled in the research trial, study personnel will discuss the research study with you in further detail, and you can be removed from the research trial anytime at your request. But in many cases, we do not believe that will be feasible or fair to expect any family to be able to process and understand their child’s current state, and then hear about and comprehend this clinical research trial with a clear mind, and then provide consent within this time window.
For this research trial, there is a special, very carefully monitored, federal accommodation that allows for “Exception From Informed Consent” that is made especially to allow for research trials like this one to take place.
For this research study, we have taken the following steps:
- The research study protocol, focusing primarily on the safety of the therapy, was reviewed in detail by the FDA.
- Once the research study was allowed to proceed by the FDA, the study protocol was presented to a broad community for feedback, in this case other families and patients with congenital heart disease. We paid special attention to make sure the population that we presented to was racially representative of the population that has experienced HIE.
- The feedback of the community consultations, and of our staff members (including bedside nurses, NICU doctors, and others), was reviewed and approved by the Institutional Review Board.
- We will post regular notifications to social media sites to let the broad community know about the research trial.
- Any patient who would not like to participate in the research trial in the unlikely event of HIE can ‘opt out’ using this form.
- Patients who have not opted-out may be enrolled without informed consent if they meet study criteria. Whenever feasible (expected to be very rare), we will obtain informed consent using the consent form [please link to consent form] attached here. In very rare cases, we may also provide an opportunity to object prior to enrolling in the research trial. The window of opportunity in which hydrogen may work is within hours of birth. In nearly all HIE situations, most families will not have even received a complete update from the care team and in most situations the patient’s clinical state will still be very uncertain. We will weigh all of these factors in deciding whether informed consent is feasible before enrolling in the research trial as to not delay therapy, and to not distract the family from focusing on the clinical situation or to coerce them due to a time pressure.
- Following enrollment, all families will be notified of their loved one’s participation in the research trial as soon as possible (in consultation with the clinical team), including a disclosure of whether or not they are receiving hydrogen. Families will have the opportunity to object to continued participation at any time. Any patient whose family objects to participation will be removed from the research trial immediately, including treatment with hydrogen.
If you would like to speak with a research study team member at any time, please contact us by email at hydrogenHIEstudy@childrens.harvard.edu or call 617-355-1651.
To opt-out of the research trial, please complete this form. If you change your mind and would like to undo this opt-out, please contact a study team member at hydrogenHIEstudy@childrens.harvard.edu or call 617-355-1651.