Approximately 3.9 million Americans are infected with the hepatitis C virus, according to the Centers for Disease Control and Prevention. The virus, which affects the liver, is spread through contact with human blood. Approximately 70 percent of infected patients suffer from chronic hepatitis C infection, which can cause cirrhosis and liver cancer. Hepatitis C is the leading indication for liver transplantation in the United States.
The most common treatment for hepatitis C virus is the combination of interferon and ribavirin. Interferon is an antiviral drug used to suppress and eradicate the hepatitis C virus. Ribavirin, also an antiviral treatment, is used in combination with interferon to enhance response rates. Ribavirin alone has not been shown to be an effective treatment for hepatitis C infection.
A recent advance in hepatitis treatment is "pegylated" interferon, which has improved pharmacokinetic characteristics compared to standard interferon, thus allowing more convenient once weekly dosing. In comparison, standard interferon treatments must be given three times a week.
In the new study, researchers from Duke and Johns Hopkins will compare three treatment regimens in 2,880 hepatitis C patients with one of two available pegylated interferon treatments -- pegylated interferon alfa-2b (trade name PEG-INTRON, manufactured by Schering-Plough Corporation) and pegylated interferon alfa-2a (trade name PEGASYS, manufactured by Hoffman-LaRoche, Inc.). Both treatments will be administered in combination with ribavirin.
The trial, named IDEAL (Individualized Dosing Efficacy vs. flat dosing to Assess optimaL pegylated interferon therapy), is sponsored by Schering-Plough Research Institute. John McHutchison, M.D., director of gastroenterology and hepatology research at the Duke Clinical Research Institute, and Mark Sulkowski, M.D., assistant professor of medicine at Johns Hopkins, will serve as co-principal investigators for the trial.
"The beginning of this trial is truly a milestone in research for treatments of hepatitis C virus," said McHutchison. "This is the first time we have directly compared these two treatments in a head-to-head manner. We hope to learn important information that will directly impact the treatment of our hepatitis C patients."
The trial will enroll patients from 100 sites throughout the United States. "A trial of this magnitude is a substantial undertaking," said Robert Califf, M.D., director of the Duke Clinical Research Institute. "In the past, trials have focused on placebo controls and enrolled small numbers of patients. A trial as large as IDEAL is planned to be will give patients and their doctors important information they need to have about treating this disease."
Dosing is one of the primary differences between the two treatments in the study, said the researchers. Pegylated interferon alfa-2a is administered in the same dose to all patients, while the dose of pegylated interferon alfa-2b is calculated based on each individual patient's weight.
"There have been other trials including one or the other of these treatments, but the two have never been directly compared" said McHutchison. "We cannot compare results from these other separate trials because of differences in study design, patient populations and other variables that prevent statistically valid interpretation of the data."
The goal of the trial is to determine which treatment results in a "sustained viral response" -- an undetectable level of virus in a patient's blood 24 weeks after the end of therapy -- in the largest proportion of patients.
"By eradicating the virus during and after therapy, we are able to forestall, and in many cases, prevent further damage to the liver. This has a huge impact on patient health and quality of life and translates into prolonged survival, a lower incidence of liver cancer and may prevent the need for liver transplantation," McHutchison said.
McHutchison has served as a paid consultant to Schering and has received research support and lectured on behalf of both Schering-Plough and Hoffman-LaRoche.