With its participation in a study concerning a cardiac side effect of the rare disorder known as Marfan syndrome, Vanderbilt Children’s Hospital is a member of an elite club, the Pediatric Heart Network.

 

Founded in 2001 and funded by the National Heart, Lung and Blood Institute (a unit of the National Institutes of Health), the PHN is a group of hospitals dedicated to research studies in children with congenital and acquired heart disease. In the past 25 years, fewer than 40 randomized clinical trials have been conducted in pediatric patients, leaving clinicians frustrated by a lack of evidence-based medicine in their field.

 

“We see a lot of patients and take care of them, but a lot of our evidence is lacking,” said Larry Markham, MD, Vanderbilt assistant professor of pediatric cardiology and the site investigator for Vanderbilt’s participation in the PHN. What’s more, limited clinical trials mean limited drug therapies for the nation’s most vulnerable cardiac patients.

 

Markham said pediatric cardiac trials face a myriad of challenges, not the least of which is that pharmaceutical companies shy away from funding. One barrier is that such studies require multiple sites because of simple demographics — there are 22 million adults with coronary disease but many fewer children … thus, several sites with just a few children at each site is the norm.

 

The PHN has completed a few studies already, has several studies ongoing and a few more in the pipeline. The Marfan trial is three years old and about three-quarters complete, Markham estimated. Nationwide, 22 sites are participating. “The goal is for 604 patients to be randomized, and it’s approaching that now. We’re happy to participate,” Markham said. At this time, Vanderbilt has 13 patients in the study, and each patient participates for three years.

 

Markham joined Vanderbilt in 2006 after a cardiology fellowship at Cincinnati Children’s Hospital. There, he was the principal investigator for the PHN Marfan trial. After his arrival in Nashville, Vanderbilt applied in 2007 and was accepted in 2008 as a Marfan trial site.

 

“When the opportunity came to add additional sites, I had already moved here, and we applied for Vanderbilt to be a site,” he recalled.

 

Marfan syndrome is an inherited disorder caused by a mutation in the gene that controls certain connective tissues. The malady is characterized by elongated bones and ligaments, and the eyes and lungs can also be affected. The PHN’s interest is because the disease can cause a dangerous weakness in the wall of the aorta. Without surgery, the aorta could enlarge and burst.

 

This study compares two drugs, Atenolol and Losartan, to see which one is better at slowing the speed of aortic enlargement. Atenolol is a beta blocker, while Losartan is an angiotensin II receptor blocker. The study also compares the side effects of both medications. “All patients are treated. There’s not a placebo group,” Markham said. “The goal is to evaluate the aortic root. In patients with Marfan syndrome, the aortic disease and aortic dissection is what shortens their life.”

 

The fact that Marfan syndrome is being studied by the PHN is the result of one man’s work. Harry Dietz, MD, a professor of medicine and genetics at Johns Hopkins University School of Medicine, has focused his career on Marfan, discovering mutations in the genetic code of connective tissue. Today’s PHN study builds on those findings.

 

“The story of the Marfan trial is pretty remarkable in and of itself,” Markham said. “He (Dietz) devoted his life to Marfan, discovered the gene involved and has really done the pioneering.”

 

While Vanderbilt is currently participating in one trial, Markham said it’s his hope to augment the institution’s PHN stature. Next year, the PHN will request application for full-fledged membership for all studies for a five-year cycle, and Vanderbilt will apply, he said.