DCRI investigators have completed the study of metronidazole, an anti-microbial agent frequently administered to infants suffering from necrotizing enterocolitis.

The Duke Clinical Research Institute has completed its first drug trial conducted for the Pediatric Trials Network (PTN).

Late last year (2011), DCRI investigators completed their study of metronidazole, an anti-microbial agent frequently administered to infants suffering from necrotizing enterocolitis (NEC). The disease, which causes the victim’s intestinal lining to die, occurs frequently in premature infants and is often fatal.

Doctors have long prescribed metronidazole to infants suffering from NEC, even though there was no reliable information about dosage amounts for children. Metronidazole was not unique in that regard. Prescription medicines are rarely packaged with information about appropriate doses for children. That began to change in 2002, when Congress passed the Best Pharmaceuticals for Children Act (BPCA), a law designed to promote pediatric drug research. The PTN, an alliance of clinical research institutions working in concert with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, was established shortly thereafter. Its goal is to provide doctors with pediatric dosing guidelines for widely prescribed medicines lacking that information. In September 2010, the National Institutes of Health awarded a $95 million contract to the DCRI’s Daniel Benjamin, MD, MPH, PhD, to oversee the first round of clinical trials under the PTN to determine appropriate dosing regimens for children. The metronidazole study began enrollment in January 2011.

The purpose of the metronidazole study was to determine the pharmacokinetics and safety of the drug in young children, and thereby determine an appropriate dosing regimen. The metronidazole trial was the first one to enroll patients and complete its study under the PTN contract. The DCRI’s Michael Cohen-Wolkowiez, MD, served as principal investigator. Barrie Harper, MT, was project leader.

The trial, which was conducted at three study centers, enrolled 24 premature infants with suspected infections. Researchers divided the infants into two groups based on their age. One group comprised infants younger than 14 days, the other included infants 14 days or older. Both groups received an equal dose of metronidazole at age-based frequencies over a period of several days. Researchers took blood samples from the infants during the trial to determine how the drug levels behaved within the infants’ bodies.

After analyzing the data, researchers intend to present their findings to the Food and Drug Administration. They hope to submit new dosing guidelines for metronidazole in infants to agency officials to update the metronidazole package insert.

“The goal of the entire PTN is to potentially modify the package inserts with meaningful dosing information for children, which doesn’t exist yet,” Harper said. “Children aren’t little adults, even though a lot of physicians dose them like little adults.”

Harper and Cohen-Wolkowiez agreed that the PTN aided the speed and efficiency of the metronidazole study. The improved communication and collaboration engendered by the network allows researchers to complete their studies on time and on budget, Harper said. The metronidazole study was finished within 18 months.

“We thought we would need a 12-month period [for enrollment],” Harper said. “We beat that.”

“The time line under which this study was completed was exceptional, and it was reached thanks to the professionalism and dedication of the DCRI team,” Cohen-Wolkowiez said. “This study will become a major player in the renewal of BPCA in 2012.”

Harper also credited the DCRI team and its partners at the Emmes Corporation, the NICHD’s data coordinating center, for the study’s success.

“Our people worked really hard on this project, and they were really excited about it,” she said. “It’s been a very collaborative effort.”