Children's Doctors Lead Groundbreaking Study
from The Children's Hospital (TCH) News, August 2006
Two Children’s Hospital doctors – who were the first ever to use inhaled nitric oxide (iNO) to treat a preemie with respiratory failure more than 10 years ago – are also the authors of a major multicenter clinical trial for iNO therapy to prevent chronic respiratory complications.
The study, published in the July 27 issue of the New England Journal of Medicine, found that use of iNO could significantly lower the risk of lung and brain damage in very low birthweight premature infants.
John Kinsella, MD, and Steve Abman, MD, from the Pediatric Heart Lung Center (PHLC) at Children’s, first used iNO in severely ill low birthweight premature infants about 15 years ago. The therapy has been approved by the FDA to treat pulmonary hypertension in term newborns, Dr. Abman said, but whether premature infants benefit from iNO therapy has been uncertain. Drs. Abman and Kinsella began studying this possible therapy – based on promising findings in the PHLC laboratory – in a pilot trial at Children’s in the 1990s.
“We became the first hospital ever to use inhaled nitric oxide to treat a premature baby with respiratory failure,” Dr. Abman said.
The results of the pilot study were promising – enough that Dr. Kinsella designed a trial to determine its safety and efficacy with funding from the National Heart, Lung and Blood Institute (NHLBI).
“These findings are the result of seven years of work, if you include its conception, design and implementation,” Dr. Abman said. “This trial is a major landmark study in this area.”
The trial, which Children’s conducted with 16 other centers over five years, looked at preterm babies on mechanical ventilators the first two days after birth. Half were treated with iNO and half received a placebo, but treatment remained blinded to care providers and families. Patients were divided into three categories based on weight. The findings, Dr. Kinsella said, are impressive.
“The babies who received nitric oxide at a low dose in the first 48 hours after birth had a 50 percent reduction in key signs of brain injury,” he said. In addition, preterm infants with a birth weight of about 2 pounds had a 50 percent reduction in bronchopulmonary dysplasia (BPD).
“Many neonatologists, once they view these findings, will change their clinical practice,” Dr. Kinsella said.
However, the children enrolled in the trial must be studied for several more years so researchers can better understand the long-term effects of treatment, Dr. Abman said.
In addition, Drs. Kinsella and Abman are pleased that this trial was the result of much collaboration throughout the hospital.
“So many people came together for this clinical trial, including laboratory and clinician scientists, to meet in a collaborative way to solve critical problems. It’s very exciting to be able to learn about something in the lab and then apply it to the bedside. It leads to novel interventions and new treatments, which are continuing to be explored in the PHLC laboratory.”
But the most important outcome of the study, Dr. Abman said, is the benefits for patients and families.
“We are especially grateful for the support of so many families for participating in this study, and are excited to offer something that can enhance long-term outcomes for premature newborns,” he said. “This is a simple intervention, and we hope it will go a long way for years to come.”
