The PTN lisinopril study completes enrollment

In spite of the challenges posed by its complex protocol, the “Safety and Pharmacokinetics of Lisinopril in Pediatric Kidney Transplant Recipients” study has completed enrollment, with a total of 26 patients contributing data to this study of lisinopril use for the control of high blood pressure in kids receiving kidney transplants.

This accomplishment is due to the exceptional efforts of the study teams at 8 sites: University of Alabama–Birmingham, Arkansas Children’s Hospital in Little Rock, University of Michigan at Ann Arbor, New York University Langone Medical Center, Albert Einstein University Hospital in New York, Cincinnati Children’s Hospital, Children’s Mercy Hospital in Kansas City, and Emory University & Children’s Healthcare of Atlanta.

Lisinopril is a drug used in children ages 6 and up to treat high blood pressure, a condition commonly seen among children and adolescents who receive kidney transplants. Unfortunately, the appropriate dose of lisinopril in these especially vulnerable patients is not currently known. This PTN study is evaluating the safety of lisinopril in pediatric participants who have a stable functioning kidney transplant and high blood pressure. It is also examining what young bodies do to the drug (a.k.a. the drug’s pharmacokinetics).

Preliminary results are expected later this year.

The Institute of Medicine releases report on pediatric studies conducted under BPCA and PREA

The Institute of Medicine (IOM) released a report today that finds that federal laws motivating or requiring drugmakers to conduct pediatric studies have yielded important information to guide the use of medications in children.

Titled “Safe and Effective Medicines for Children: Pediatric Studies Conducted Under the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act,” the report also notes that studies involving children continue to be limited and suggests avenues to improvement, such as strengthening the design and execution of pediatric studies requested under BPCA or required by PREA, as well as expanding the research scope to include more long-term safety studies and studies in neonates.

The report’s release precedes the 2012 Congressional vote on reauthorization of both BPCA and PREA, which occurs every five years. As directed by Congress, the Food and Drug Administration (FDA) asked the IOM to convene a committee to review aspects of pediatric studies and changes in product labeling that resulted from these legislative acts. Of note, since the two policies were adopted, the FDA has approved 400 labeling changes for drugs used in children.

More information about the IOM report may be found at: http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=13311.

PTN study of clindamycin dosing in obese children enrolls first patients

The University of Louisville in Kentucky and Children’s Mercy Hospital of Kansas City, Missouri, have enrolled the first two patients into the PTN study of the safety and pharmacokinetics of clindamycin in obese children. Principal investigators Michael Smith, MD, (Louisville) and Jen Goldman, MD, (Children’s Mercy) both enrolled their participants on August 8, marking the start of this trial to determine optimal dosing of the drug in young people with a body mass index ≥85th percentile for age.

Clindamycin is considered a first-line therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), an infection that often occurs in obese patients. Because excess weight results in altered body composition, physiology, and resulting changes in drug distribution, dosing guidelines based on normal weight adults cannot be extrapolated to their overweight and obese counterparts, and especially not to obese children.

Rates of childhood obesity have risen over the past decade, thus making it critical that safety and efficacy studies of drugs used in kids and adolescents be conducted to ensure effective treatment. The PTN clindamycin study will help to fill this knowledge gap; initial results are anticipated in mid 2014.

The fluconazole prophylaxis study locks its database

The PTN team behind the Safety of Fluconazole Prophylaxis in Infants study successfully locked the Benjamin study database last week. To evaluate the safety of fluconazole, the team is gathering randomized trial datasets from several thought leaders to perform a data meta-analysis—the Benjamin study comprises the first of these datasets. The PTN will examine safety data from these earlier randomized controlled trials of fluconazole prophylaxis to prevent candidiasis in very low birth weight and extremely low birth weight infants. Infants born <28 weeks gestational age are susceptible to this disease, which can lead to death or neurodevelopmental impairment.

The Benjamin study was a phase 3, randomized, blinded, multicenter, placebo-controlled trial comparing the efficacy of fluconazole administration to placebo for the prevention of neonatal candidiasis in infants <750 grams birth weight. The primary purpose of the trial was to evaluate death or candidiasis at study day 49 and to determine the safety and efficacy of fluconazole in this context.

The PTN team will analyze this and the other datasets to study primary safety outcomes, including gastrointestinal events, adverse events, serious adverse events, and laboratory values. By cultivating a better understanding of the potential safety issues involved with treating low birth weight infants with fluconazole, we hope to use the drug to better prevent the devastating results of candidiasis in this vulnerable population.

A busy week for the PTN sildenafil trial

The week of February 18–22 saw many milestones in the PTN sildenafil trial. On Tuesday, the first investigator’s meeting was held. By Wednesday, the trial’s first two sites had been activated — one at the Medical University of South Carolina Children’s Hospital (MUSC) and the other at the University of North Carolina–Chapel Hill. And, on Thursday, MUSC enrolled the trial’s very first patient.

Congratulations to the MUSC site team—Dr. Andrew Atz (principal investigator) and Patricia Infinger (study coordinator)—for their swift action in helping to kick off this important study!

The PTN sildenafil trial is evaluating the pharmacokinetics and safety of sildenafil in preemies suffering from bronchopulmonary dysplasia, the most common health problem associated with premature birth. Up to 20% of infants with bronchopulmonary dysplasia develop pulmonary arterial hypertension, and up to 40% of these infants die. Currently, few drugs are available to prevent bronchopulmonary dysplasia, and none can reduce death among infants with bronchopulmonary dysplasia and pulmonary arterial hypertension.

Sildenafil is approved by the FDA for the treatment of pulmonary arterial hypertension in adults, but its effectiveness in children has not been determined. In spite of this knowledge gap, sildenafil is increasingly being used off-label in premature infants at risk for or diagnosed with pulmonary arterial hypertension. The PTN hopes to establish the best dose of the drug to reduce pulmonary arterial hypertension in these fragile patients, thereby reducing the potential for harm and optimizing outcomes.

Find out more about the PTN sildenafil trial at clinicaltrials.gov.

The PTN anti-staph trial marks its first enrollment

Dr. Barry Bloom and Ms. Paula Delmore at Wesley Medical Center in Wichita, Kansas, have enrolled the first baby into the Pharmacokinetics of Anti-staphylococcal Antibiotics in Infants trial. The infant—born at 24 weeks gestation and now 52 days old—is receiving clindamycin, one of three anti-staphylococcal antibiotics routinely used in preemies to treat staphylococcal infections.

Seventy percent of late-onset infections in the neonatal intensive care unit are due to staphylococcal species, many of which are methicillin-resistant. Infants with these infections experience long hospitalizations and have an increased risk of septic shock, severe necrotizing pneumonia, and neurodevelopmental impairment, as well as a high risk of death (up to 40%). Rifampin, clindamycin, and ticarcillin-clavulanate are used to fight staphylococcal species, but the correct dosing and safety of these antibiotics has not been established for all infant populations.

This study will measure the levels of rifampin, clindamycin, or ticarcillin-clavulanate in enrolled babies, thereby gauging how the infant body absorbs and distributes the drugs. By understanding these pharmacokinetic properties, we can determine the best doses for treating staphylococcal infections in these vulnerable patients.

The trial will enroll up to 32 infants for each drug. The drugs will be given over 2–4 days, and the infants will be monitored for another 7 days for any drug side effects. To find out more about this study, visit ClinicalTrials.org.