Sepsis – a life-threatening inflammatory condition triggered by the body’s massive response to an infection – is diagnosed in about 75,000 children in the U.S. each year and causes about 7,000 deaths. The condition can escalate so rapidly that national guidelines recommend treatment begin within 20 minutes of a patient’s arrival to the emergency department.
A clinical trial led by Washington University School of Medicine in St. Louis at St. Louis Children’s Hospital will evaluate the safety and effectiveness of the type of fluid given to children with sepsis, and determine whether such fluids can reduce the incidence of acute kidney damage or improve survival. Children treated for sepsis typically receive fluids – often through an IV – to help rehydrate the body, improve blood pressure and facilitate the administration of other medications, such as antibiotics.
Patients in the trial will be randomly assigned to receive one of two types of fluids – unbuffered saline or a buffered solution, such as lactated Ringer’s or Plasmalyte. While both types of fluids have been shown to have a benefit in children with sepsis, preliminary data suggest that buffered solutions may be more effective, although the saline solution is more commonly used.
The clinical trial at St. Louis Children’s is part of a national trial led by the Children’s Hospital of Pennsylvania. An estimated 6,000 children nationwide will be enrolled in the trial at 30 U.S. hospitals.
“Sepsis is a scary condition, and there is no single treatment or medication that is effective,” said Lindsay Clukies, MD, a Washington University pediatric emergency physician who is leading the trial at St. Louis Children’s. “Pediatric emergency physicians have considerable experience treating children with sepsis, but one of the major unanswered questions is whether one type of fluid is better than another other in rehydrating patients and improving outcomes. This trial is designed to answer that question.”
For a child with sepsis, survival depends upon receiving aggressive therapy quickly, which can leave little time to discuss the trial with parents or guardians to obtain informed consent. In such cases, the U.S. Food and Drug Administration allows for an exception from informed consent so that patients can be enrolled into a trial within the critical time frame necessary to evaluate the treatment.
The trial’s design and the exception from informed consent were approved by the FDA and the Children’s Hospital of Pennsylvania’s Institutional Review Board. Such boards review research protocols to ensure clinical trials are ethical and that the rights and welfare of study participants are protected.
Patients for whom the emergency room doctor suspects septic shock will be enrolled and treated with one of three commonly used fluids. Then, as soon as possible, the study team will inform the parent/guardian about the study and seek permission to continue in the study and to use their child’s data. Thus, the ultimate choice to remain in the study will always be with the parent/guardian. Notably, both types of fluids being evaluated in the trial are considered “standard of care” for sepsis, and so all children will receive an appropriate treatment option.
However, families may choose to opt out of participation by visiting the study website. They will then receive a bracelet in the mail that their child can wear, or that the parent or caregiver can hold for them. The child’s name also will appear on an opt-out list that clinicians consult prior to enrolling any child in the clinical trial. For any children enrolled in the trial, parents and/or guardians may withdraw them from the study at any time.