Study Details
Why are we doing this research study?
A cardiac arrest is a life-threatening medical emergency in which blood flow to the body and heart stop. When cardiac arrest goes on for more than a few minutes, brain damage to the brain, kidneys, and other organs can occur. This injury is an important contributor the poor survival rates in patients who have a prolonged cardiac arrest, even when rescue using ECMO. There is currently no way to actively treat the injury that occurs from a cardiac arrest.
Hydrogen may be able to help
Many studies have been performed demonstrating that when hydrogen is given to during an injury like cardiac arrest, the damage is much less. Boston Children’s is a leading research center for hydrogen as a therapy in the United States, and has extensive experience with hydrogen use.
For example, this paper showed that when hydrogen was given to animals experiencing an injury similar to the ones in this trial, brain damage decreased from the area shown in red (controls) to that shown in blue due to treatment with hydrogen. In this research study, hydrogen was given in the same ways that we will give it in this research study – through the ventilator and ECMO membrane.
In another research study at Boston Children's Hospital, we showed in this paper that administering hydrogen at the dose that we will use in this research study is safe and well tolerated in healthy adults.
A recent research study from Japan demonstrated that the administration of hydrogen in adults following a cardiac arrest was safe, improved survival, and improved neurologic outcomes in patients who survived.
Patients cannot be treated with hydrogen unless they are enrolled in this trial.
Who?
Patients hospitalized at Boston Children’s Hospital or Texas Children’s Hospital who have a cardiac arrest for longer than five minutes, and the decision is made to resuscitate the patient using ECMO (i.e. ECPR). Patients who have not opted out will be enrolled in the research trial by the treating team at the time of cardiac arrest and decision to cannulate for ECMO.
How?
If a patient’s ICU team determines that they need to place the patient onto ECMO in the setting of ECPR, the patient may be enrolled in the Hydrogen-FAST study immediately. Patients will be randomly assigned to be treated with 2% hydrogen or not – starting as soon as possible during CPR (ideally before ECMO begins) 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. Patients will be followed daily by our research team, alongside your clinical team, for 30 days after the ECPR event and the chart reviewed at six months to assess functional outcomes.
We estimate that the entire research study will take three years to complete.
What other therapies are available to treat the injury that occurs after ECPR?
The majority of care following an ECPR episode is focused on supporting the patient as the body recovers from this injury. This includes 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), and avoiding fevers, which can cause additional injury to the body. 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 Hydrogen-FAST Study
In most cases, informed consent will not be possible. The use of EMCO in the setting of CPR is always an emergency, and is always unexpected event. If the clinical team expected that they patient would have a cardiac arrest, they would place a patient onto ECMO support before a cardiac arrest happened. An ECPR event is overwhelming. The healthcare team is busy performing CPR and often placing a breathing tube emergently. Many pieces of equipment are brought into the room, surgical staff arrive transform the ICU room into a sterile operating room, and the ICU staff administer anesthetic medications. Family members are often watching, trying to grasp what is happening with their child. After the ECPR event, the priority for communication is to help family members understand what happened, and the current status of the patient, and what to expect.
Hydrogen is most effective when started immediately, and must be given within two hours of the event. 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 study 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 payed special attention to make sure the population that we presented to was racially representative of the population that has experienced ECPR.
- The feedback of the community consultations, and of our staff members (including bedside nurses, heart surgeons, ICU doctors, and others), was reviewed and approved by the Institutional Review Board.
- Since we started the research study, we post regular notifications to social media sites to let the broad community know about the research trial.
- Every patient who seen preoperatively in the Heart Center or admitted as an inpatient receives a small informational pamphlet (which may be how you ended up here!).
- Any patient who would not like to participate in the research trial in the unlikely event of ECPR 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, 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 <2 hours from the onset of cardiac arrest. In nearly all ECPR 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 tenuous and 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 hydrogenfast@childrens.harvard.edu or by phone at 857-299-4233.