News

Therapeutic Hypothermia After
Cardiac Arrest in Children (THAPCA) Trials:

Can lowering body temperature prevent brain damage in children?

University of Michigan C.S. Mott Children's Hospital and University of Utah lead study of therapeutic hypothermia to prevent brain damage in children who suffer cardiac arrest
ANN ARBOR, Mich. - In the first large-scale study of its kind, researchers at the University of Michigan C.S. Mott Children’s Hospital and the University of Utah will lead a multi-center study to investigate whether hypothermia–lowering body temperature–can prevent or reduce brain damage in children deprived of oxygen after a cardiac arrest.
The Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) http://www.thapca.org/ Trials begin this fall. The National Heart, Lung and Blood Institute, part of the National Institutes of Health, will provide funding for the Vanguard phase, and pending successful completion of that phase, for a total of six years of subject accrual from 30 trial sites, and up to 900 participants in the United States and Canada.
Frank W. Moler, M.D., M.S., medical director of the Mott pediatric intensive care unit and professor of pediatrics at the U-M Medical School, is the scientific principal investigator, while J. Michael Dean, M.D., MBA, H.A., and Edna Benning Presidential professor of pediatrics at the University of Utah School of Medicine and Primary Children’s Medical Center, Salt Lake City, is principal investigator for the data center.
Every year, thousands of children suffer cardiac arrest as complications from illnesses or as the result of accidents, such as near-drowning.
When the heart stops working during a cardiac arrest, the body’s blood supply is interrupted and cells are deprived of oxygen. Brain cells are particularly vulnerable to oxygen loss, leading to sometimes devastating brain damage in children.
“Cardiac arrest in children is a tragic event that usually leads to death, or long term disability in survivors,” says Moler.  “Currently no therapies have been shown to improve children’s chances of recovering.”
The THAPCA Trials will look at children who experience cardiac arrest while already hospitalized and have cardiac arrest related to another condition or disease and those who have cardiac arrest after an event or sudden illness outside the hospital.
Children in the trials will be randomly assigned into two actively managed therapy groups: those whose body temperatures will be lowered to 32-34 degrees C through surface cooling called therapeutic hypothermia and those whose body temperatures are actively kept in the normal range 36.0-37.5 degrees C also by surface cooling, sometimes called therapeutic normothermia.
In the initial funding for the Vanguard phase, U-M has received $2.3 million to get the trials underway and the University of Utah has received $1.3 million.
“Performing definitive studies, that allow researchers to examine therapies like therapeutic hypothermia, is challenging because it depends on the cooperation of multiple children’s hospitals and significant financial resources,” Moler says.
Along with the academic medical centers and clinical sites, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and Collaborative Pediatric Critical Care Research Network, and the Health Resources Services Administration Emergency Services for Children program’s Pediatric Emergency Care Applied Research Network participated in the development of the THAPCA trials.

 

Use Of Lorazepam for the Treatment of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial of Lorazepam and Diazepam

The Pediatric Seizure Study

Every day around the country, children who suffer severe seizures due to epilepsy, head injuries or other causes are treated in emergency rooms with one of two different drugs: lorazepam or diazepam (also known as Ativan and Valium).

But doctors don’t know which of the drugs is more effective, because the two have never been compared directly in children. So, 10 hospitals around the country – including the University of Michigan Health System -- have joined together to study this issue. The study will randomly assign children experiencing severe seizures to receive either lorazepam or diazepam, and then look for differences in how the drugs act.

When a child has severe, prolonged and life-threatening seizures (a state called “status epilepticus”), treatment should be given in the first five minutes after they arrive at the hospital. So, children will be treated before their parents or legal guardians can give an “informed consent” – that is, before they can be told all the details of the study and sign a document allowing the child to be enrolled.   According to federal law, this special situation means that before the U-M team can begin the study, they must inform the public and allow community members the chance to comment on it. Parents may also register their preference to “opt out” of the study in advance by adding their child’s name to a list.

Individuals may read more about the study at  www.dcchildrens.com/seizurestudy or call 1-877-661-4666 to request information, make comments or ask that their children not be enrolled in the study if they are brought to the U-M emergency department in status epilepticus. Children’s Hospital of Michigan in Detroit is also participating in the study; parents only need to call once – both hospitals will receive any messages left.

“We want to make sure that parents and providers have a chance to learn about this study, and why we are doing it, before we begin,” says Rachel Stanley, M.D., MHSA, a and the leader of the study at U-M.

“This is an important effort to study emergency treatment in a scientific way, so that we can improve the care of children with seizures,” she adds. Stanley is a U-M assistant professor of emergency medicine and pediatrics. She directs the Great Lakes Node of the Pediatric Emergency Care Applied Research Network, which is based at U-M and conducts a broad range of research on emergency treatment of children.

The seizure study is the second U-M study to reach this stage of informing the public and seeking public comment. The first, which involves devices used in cardiopulmonary resuscitation (CPR), is now under way in tandem with St. Joseph Mercy Health System and Huron Valley Ambulance.  Both are examples of a kind of study in which critically ill people are treated on an emergency basis before they or their legal representatives can give informed consent. In very specific conditions, this type of research is allowed under a U.S. Food and Drug Administration ruling called Exception from Informed Consent or EFIC.

To protect the rights and safety of patients, every EFIC study must be carried out according to special rules, and with extra scrutiny from an independent panel called an Institutional Review Board. In fact, even though the FDA began allowing EFIC studies nationwide in 1996, the U-M Institutional Review Board for medical research has only recently begun to consider applications for this type of research after reviewing the experience that other hospitals have had with EFIC studies. To learn more about this, visit www.med.umich.edu/opm/newspage/2007/emergencystudy.htm.

The Pediatric Study is sponsored by The National Institute of Child Health and Human Development (NIH), with support from the Emergency Medical Services for Children of the Maternal Child Health Bureau, Health Resources and Services Administration. Both are agencies of the federal government.  It will involve children between the ages of 3 months and 18 years.

Unless they are on the “opt out” list or have other characteristics that make them ineligible for the study, all children in status epilepticus seizures who are brought to the U-M emergency department during the study period will be randomly assigned to receive one of the two medicines that have been proven to treat seizures. They will receive all care that they would normally receive during their stay at the hospital.

If a parent or guardian is with a child when he or she arrives at the emergency department, they can tell the doctors or nurses that they do not want their child to be in the study. After a child has been treated, parents or legal guardians will still have an opportunity to take a child out of the study, and their care will not be affected.

Children who remain in the study may receive additional blood tests beyond the usual care, and their parents or guardians will be contacted for an interview about a month after the child is treated. Parents will receive compensation for the time spent on the study.
By the time they turn 15, as many as 8 percent of all children will experience some sort of seizure. Status epilepticus is an especially severe form of seizure, and can cause brain damage and even death if not treated immediately.

Both lorazepam and diazepam are commonly used to treat seizures in children, but only diazepam has been approved by the FDA specifically for use in children. Lorazepam can be prescribed by physicians on an “off label” basis. Both drugs are considered safe, though they both have some side effects.