Wednesday, January 23, 2008

DCRI researchers complete first study on anti-clotting drugs for children
By Kelly Winget

Even though children often respond to drugs differently than adults, many medications haven't been tested on children. When doctors are treating infants or young children with heart problems, they are often forced to make educated guesses about proper dosing, according to the DCRI's Jennifer Li, MD, MHS.

Li, chief of pediatric cardiovascular research, led the first-ever global study on an anti-clotting drug in children under the age of two. For the study, 22 research centers tested clopidogrel, also known as Plavix, in what is known as the PICOLO Trial. Results will be published in the January 29 issue of Circulation.

“We were astonished at how little of the drug they needed to reap the same benefits as adults,” said Li. “It was only about a fifth of the amount that we were expecting.”

Clopidogrel helps to prevent blood clots, and adult studies have shown that it can help prevent heart attacks, stroke or death in patients with heart disease. Doctors believe that the drug would also significantly benefit children but were uncertain of the safest, most effective dose.

Pediatric dosing is not as straightforward as thinking that if a child weighs one-eighth of what an adult does, that the child should receive one-eighth of the adult dose, said Li. Children metabolize drugs at a different rate, and their bodies are changing much faster.

The study enrolled 92 children, all of whom had heart disease and were at risk for developing potentially fatal blood clots. Most of the children had a disorder involving a poorly performing, small ventricle. The disorder, hypoplastic left heart syndrome, makes them weak and bluish in color. Other children in the study had imperfect heart valves and one child had a condition that causes inflammation in the coronary arteries. Three-quarters of the children had shunts implanted in their hearts to help improve blood flow.

Patients were randomized into one of two groups. One group received a placebo, and the other received clopidogrel. The patients in the clopidogrel group were given one of four doses, which ranged from .01 to .20 milligrams per kilogram of weight. They were put on the drug between one to four weeks.

An average adult weighs 75 kilograms and receives 75 milligrams of clopidogrel daily to prevent clots, said Li. Following that formula, it would seem that the most effective dose for children under the age of two would be one milligram per day. But according to the study, the optimal dose for infants and toddlers was only .2 milligrams.

Further studies might be necessary to analyze potential side effects. One patient developed a lower platelet count during the treatment.

Other DCRI researchers involved in the trial were Eric Yow and Katherine Berezny.