Building the Evidence Base for Treatment of Severe PARDS

Jan 21 2019

Building the Evidence Base for Treatment of Severe PARDS

Looking into the eyes of a distressed parent, you want to be able to tell them you’re providing interventions that are based on good evidence for the care of their child. When a gap in knowledge prevents that clinical confidence, Martha Curley, RN, PhD, FAAN, pediatric critical care nurse and research scientist, is there to help find answers.

“The main reason I completed a PhD in nursing science was so I could ask and answer questions relevant to the patient population I cared for as a critical care nurse,” said Dr. Curley, professor of nursing and Ruth M. Colket Endowed Chair in Pediatric Nursing, Children’s Hospital of Philadelphia, and professor of anesthesia and critical care medicine, Perelman School of Medicine at the University of Pennsylvania.

An early research interest for Dr. Curley was optimal positioning for patients with pediatric acute respiratory distress syndrome (PARDS). Among the questions she has considered during her career is whether or not patients with severe PARDS, as defined by an expert panel, could benefit from prone positioning while ventilated, and if conventional mechanical ventilation or high-frequency oscillatory ventilation (HFOV) are most effective in improving ventilation. With her PROSpect: Prone and Oscillation Pediatric Clinical Trial, funded by the National Heart, Lung, and Blood Institute, she aims to provide data that will support evidence-based practice.

Casting a Wide Net

PROSpect is Dr. Curley’s third funded multisite randomized clinical trial but first international study.  Her co-principal investigators are Ira Cheifetz, MD, FCCM, FAARC, professor of pediatrics and anesthesiology, executive director and chief medical officer, Duke Children’s Hospital, Durham, N.C., and Martin Kneyber, MD, PhD, FCCM, chief, Division of Critical Care Medicine, Beatrix Children’s Hospital, The Netherlands.

With the goal of recruiting 1,000 children with severe PARDS, the researchers knew they’d need numerous sites. Units participating in PROSpect must already be using the therapies to be evaluated as part of their usual practice. Additionally, onsite extracorporeal membrane oxygenation backup is required in case a patient is unresponsive to the PROSpect protocol. The potential for geographically based differences in treatment protocols was not considered an obstacle, as treatment for severe PARDS is based on international agreements of therapies. Dr. Curley and her team found over 45 international centers that will enable them to enroll the greatest number of children in the shortest amount of time.

The 45-site, two-by-two factorial, response-adaptive, randomized controlled clinical trial will compare pediatric patients randomized to supine versus prone positioning and to conventional mechanical ventilation versus HFOV. In current practice, pediatric critical care clinicians turn to these interventions, but without a clinical trial showing outcome benefits for either approach for PARDS, treatment is often based on clinician preference at the time of implementation and decisions drawn from adult-based data.

“We just don’t know how best to recommend these therapies,” Dr. Curley said. “At the end of this study we’ll be able to make recommendations, even if those recommendations are to drop prone positioning and/or the oscillator. But then we’ve got our answer and can go on to the next important question.”

This study will provide the definitive evidence needed for the field to consider a major change in clinical practice in the care of critically ill children with severe PARDS.

New Approach to Data Collection

The PROSpect trial is designed to enroll up to 1,000 participants, but after 400 patients are enrolled, the statistical team will review the data and change the randomization probabilities so patients are more apt to be assigned to the more superior treatment.

“It’s an unusual approach that will hopefully answer our question as quickly as possible,” Dr. Curley said. “Safety is most important. As a clinical trialist, you want to be able to look a parent in the eye and say we just don’t know what the superior treatment is and we need to figure that out. So, while this study may not benefit your individual child, what we learn from your individual child will be paid forward for other kids who have this horrible disease.”

While she does not have a prediction for what her study will find, Dr. Curley is confident PROSpect will answer the question, whether that be a combination of therapies or none at all.

“We are giving members of the healthcare team the data they need to feel confident in the care they are providing,” Dr. Curley said. “We need good evidence when we are dealing with very sick children.”

Reality of Recovery

A key element of the PROSpect trial involves yearlong follow-up to assess the quality of life of children with PARDS who are discharged. Dr. Curley said current data shows approximately 70 percent of children with PARDS survive, but beyond that, information is scarce.

“We don’t know much about what happens with these kids following discharge,” Dr. Curley said. “We know that kids are highly resilient; they have such capacity for healing depending upon their age when this illness hits, and there may not be long-term issues in pediatrics as we have in adults.”

Dr. Curley will build on work she’s already begun in a sub-study of her RESTORE study cohort, “Long-Term Outcomes after Protocolized Sedation versus Usual Care in Ventilated Pediatric Patients,” that followed patients to evaluate long-term effects such as the cognitive impact of critical illness on children as they advance in school.

“We want to make sure our therapies for children optimize their chances for good quality of life,” Dr. Curley said. “We need to look beyond the intensive care unit at survival and the quality of that survival.