PTN lisinopril study and subsequent label change highlighted in DCRI News.

Pediatric Trials Network study results in label change for hypertension drug

May 11, 2016 – The change could affect the hundreds of children who are prescribed lisinopril after kidney transplants each year.

A study conducted by the Pediatric Trials Network (PTN) has resulted in a labelling change for a widely used drug.

Lisinopril is an angiotensin converting enzyme inhibitor that is commonly prescribed to treat high blood pressure or heart failure in adults. It is also given to children who have hypertension, including children who have undergone kidney transplants. As with many other drugs, however, there has been little research to suggest the optimal dose for pediatric transplant patients. The PTN was established to answer these types of questions about drugs given to children and adolescents.

“There is a great medical need but a small market for these types of studies,” said Daniel Benjamin, Jr., MD, MPH, PhD, the PTN’s principal investigator (pictured). “This is why the PTN was formed—to conduct the studies that no one else will.”

A study led by DCRI researcher Uptal Patel, MD, and other researchers for the PTN recently resulted in a decision by the the U.S. Food and Drug Administration (FDA) to update the label for lisinopril. In addition to Patel, the study’s authors included Howard Trachtman, MD, of New York University; Adam Frymoyer, MD, of Stanford University; Laurence Greenbaum, MD, PhD, of Emory University; Daniel Feig, MD, PhD, of the University of Alabama at Birmingham; Debbie Gipson, MD, of the University of Michigan; Bradley Warady, MD, of Children’s Mercy Hospital of Kansas City; Jens Goebel, MD, of Cincinnati Children’s Hospital; and George Schartz, MD, of the University of Rochester.

The study was a multicenter, open-label pharmacokinetic study of daily oral lisinopril in 22 children, aged 7–17 years, with stable kidney function following transplant.

The researchers found that the pharmacokinetics of lisinopril in children who underwent kidney transplant were similar to hypertensive children who did not receive kidney transplants. Lisinopril was generally well tolerated by the patients and was accompanied by a lowering of blood pressure at approved pediatric doses in the study population.

The results of the study were published in the July 2015 issue of Clinical Pharmacology & Therapeutics.

Approximately 1,200 children in the United States develop end-stage renal disease (ESRD) each year. Because kidney transplantation has become the primary method of treating ESRD for children, many of these patients will be prescribed lisinopril. As a result of the FDA’s recent decision, Benjamin noted, doctors will now have a better understanding of the correct dose.

“This has been a problem for over 60 years, and we’re only now addressing it,” he said. “With the PTN, we now a have a vehicle to make those changes.”

Project babyTAPE Measures Up

babyTAPEOn December 18, 10 days ahead of schedule, the PTN babyTAPE team enrolled its 2,000th participant.

On January 29, the babyTAPE databse was locked.

The data collected in the babyTAPE study will be used to develop, design, and validate a weight estimation tool, similar to what is pictured, specific to infants.

The study is chaired by Dr. Susan Abdel-Rahman from Children’s Mercy Hospital in Kansas City, MO.  The PTN Program is chaired by Dr. Danny Benjamin and operationalized by Katherine Berezny (Program Manager at DCRI).

Timolol for Infantile Hemangiomas under Review

Since first reported in 2008 that propranolol, a beta blocker, was effective in the treatment of Infantile Hemangiomas (IH)—a birthmark that most commonly appears as a rubbery, bright red nodule of extra blood vessels in the skin, commonly called a “strawberry”—this class of drug has been used as the first line of therapy for infants with IH. Timolol, also a beta blocker, is available in topical formulation, and increasingly used off-label for small, non-complicated IH. The popularity of timolol is likely due to its perceived safety as a topical drug. However, data on timolol efficacy, safety and pharmacokinetics are limited.

Under the protocol thought leadership of Dr. Beth Drolet, Principal Investigator, the PTN’s Timolol study will enroll 100 infants between the ages of ≥32 to <50 weeks postmenstrual age. The infants will be treated with timolol for 28 days then randomized into 2 groups. One group will continue timolol treatment while the other will be withdrawn from treatment. Both groups will remain on the study in their respective groups for up to 120 days. The study will begin to enroll in the early summer of 2016 in approximately 10 US sites, and will end in the fall of 2017. The data received from the study will be presented to the FDA to support the use of timolol for the treatment of IH.

PTN Pantoprazole Study Closes Enrollment

Congratulations to the PTN Pantoprazole Study Team for closing enrollment with 41 subjects. The study goal was to enroll 40 subjects in two age groups. The dedicated team worked hard to keep the study on track and accomplish this goal.

The Pantoprazole Study will evaluate the pharmacokinetics of pantoprazole in obese children and adolescents with gastroesophageal reflux disease (GERD) following administration of an oral dose of pantoprazole.