Commonly used 3-drug regimen for idiopathic pulmonary fibrosis found harmful

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, has stopped one arm of a three arm multi-center, clinical trial studying treatments for the lung-scarring disease idiopathic pulmonary fibrosis (IPF) for safety concerns. The trial found that people with IPF receiving a currently used triple-drug therapy consisting of prednisone, azathioprine, and N-acetylcysteine (NAC) had worse outcomes than those who received placebos, or inactive substances.

"These findings underscore why treatments must be evaluated in a rigorous manner," said Susan B. Shurin, M.D., acting director of the NHLBI. "This is widely used in patients with IPF, but has not previously been studied in direct comparison to a placebo for all three drugs."

The interim results from this study showed that compared to placebo, those assigned to triple therapy had greater mortality (11 percent versus 1 percent), more hospitalizations (29 percent versus 8 percent), and more (31 percent versus 9 percent) and also had no difference in lung function test changes. Participants randomly assigned to the triple- therapy arm also remained on their assigned treatment at a much lower rate (78 percent adherence versus 98 percent adherence).

"Anyone on some combination of these medications with questions or concerns should consult with their and not simply stop taking the drugs," said Ganesh Raghu, M.D., professor of medicine at the University of Washington, Seattle and a co-chair of this IPF study. "It is important to realize that these results definitively apply only to patients with well-defined IPF and not to people taking a combination of these drugs for other or conditions."

The other two study arms, or intervention groups, of this IPF trial comparing NAC alone to placebo alone will continue. In stopping this part of the trial, the NHLBI accepted the recommendation of the Data and Safety Monitoring Board (DSMB) – an independent advisory group of experts in lung disease, biostatistics, medical ethics, and clinical trial design. The DSMB has been monitoring the study since it began.

This study, called PANTHER-IPF (Prednisone, , and N-acetylcysteine: A Study that Evaluates Response in ) was designed and conducted by the Idiopathic Clinical Research Network, funded by the NHLBI. The PANTHER-IPF study was designed to evaluate whether this commonly used triple-therapy regimen could slow disease progression and improve lung function in people with moderate IPF.

PANTHER-IPF was the first study in IPF comparing the effectiveness of this combined treatment to a placebo for all three drugs. Each participant had a one in three chance of being randomized to receive the triple drug regimen, NAC alone, or placebo for a period of up to 60 weeks.

"We will continue to analyze the data to try to understand why this particular combination may be detrimental in people with IPF," said Fernando Martinez, M.D., professor of medicine, University of Michigan, Ann Arbor and co-chair of the PANTHER-IPF study. "The results are not explained by any differences between the two groups before the treatments started."

IPF is a progressive and currently incurable disease characterized by the buildup of fibrous scar tissue within the lungs. This accumulation of scar tissue leads to breathing difficulties, coughing, chest pain, and fatigue. Approximately 200,000 people in the United States have IPF. The cause or causes of IPF remain unknown; as a result treatment options remain limited. PANTHER-IPF began enrollment in October 2009.

The study had enrolled 238 of a planned 390 participants prior to the stop announcement. Participants ranged from 48 to 85 years of age, with an average age of 68. The placebo and NAC arms will continue enrolling and following their participants, and this part of the PANTHER-IPF study is expected to be completed by late 2013.

More information: What is Idiopathic pulmonary fibrosis? www.nhlbi.nih.gov/health/health-topics/topics/ipf/

Find more information about this clinical trial at clinicaltrials.gov/ct2/show/NCT00650091

Provided by National Institutes of Health

not rated yet
add to favorites email to friend print save as pdf

Related Stories

Hope for patients with mild idiopathic pulmonary fibrosis

May 18, 2010

A new therapy shows promise for patients with mild idiopathic pulmonary fibrosis. According to researchers in Japan, inhaled N-acetylcysteine (NAC) monotherapy preserves more lung function in some idiopathic pulmonary fibrosis ...

IPF drug fails in new trial

Apr 08, 2011

A new study has demonstrated no significant benefit of taking the drug bosentan for idiopathic pulmonary fibrosis (IPF).

Rare lung disease cells indicate higher death risk

Jan 16, 2008

Large numbers of certain cells in the lungs of patients diagnosed with idiopathic pulmonary fibrosis may increase their chance of death, University of Cincinnati (UC) researchers have discovered.

Recommended for you

Swatting chikungunya

2 hours ago

Summer days may be waning, but health officials are still on high alert for new cases of chikungunya, a painful mosquito-borne virus that spread to the United States from the tropics earlier this year. ...

Sierra Leone readies for controversial Ebola lockdown

2 hours ago

Sierra Leone prepared Thursday for an unprecedented three-day nationwide lockdown to contain the deadly spread of the Ebola virus in a controversial move which experts claimed could worsen the epidemic.

Nepal adopts jab to boost polio fight

2 hours ago

Nepal on Thursday launched a drive to eradicate polio by supplementing oral vaccines with an injection that experts say will boost children's immunity against the disease.

User comments