Clinical Trial Seeking Idiopathic Pulmonary Fibrosis Treatment for Older People Halted
Deadly disease usually affects middle-aged and older adults; 3-drug regimen more harmful than placebo
Oct. 22, 2011 One
part of a clinical trial studying treatments for the lung-scarring and deadly disease idiopathic pulmonary fibrosis (IPF) has been halted by
the National Heart, Lung and Blood Institute for safety concerns. IPF is a serious disease that usually affects middle-aged and older adults.
IPF has no cure and many people live only about 3 to 5 years after diagnosis.
The average age of the participants in this trial was 68. 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
Two parts of the trial were continued.
"These findings underscore why treatments must be evaluated in a rigorous manner," said Susan B. Shurin, M.D., acting
director of the NHLBI.
"This combination therapy 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 serious adverse events (31 percent versus 9 percent)
● and also had no difference in lung function test changes.
What Is Idiopathic Pulmonary Fibrosis?
Pulmonary fibrosis (PULL-mun-ary fi-BRO-sis) is a disease in which tissue deep in
your lungs becomes thick and stiff, or scarred, over time. The formation of scar tissue is called fibrosis.
As the lung tissue thickens, your lungs can't properly move oxygen into your
bloodstream. As a result, your brain and other organs don't get the oxygen they need. (For more information, go to the
"How the Lungs Work" section of this article.)
Sometimes doctors can find out what's causing fibrosis. But in most cases, they can't
find a cause. They call these cases idiopathic (id-ee-o-PATH-ick) pulmonary fibrosis (IPF).
IPF is a serious disease that usually affects middle-aged and older adults. IPF
varies from person to person. In some people, fibrosis happens quickly. In others, the process is much slower. In some people, the
disease stays the same for years.
Genetics may play a role in causing IPF. If more than one member of your family has
IPF, the disease is called familial IPF.
Research has helped doctors learn more about IPF. As a result, they can more quickly
diagnose the disease now than in the past. Also, researchers are studying several medicines that may slow the progress of IPF. These
efforts may improve the lifespan and quality of life for people who have the disease.
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 health care
provider 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 lung diseases or conditions."
Two arms of study to continue
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, Azathioprine, and N-acetylcysteine: A Study that Evaluates Response in
Idiopathic Pulmonary Fibrosis) was designed and conducted by the Idiopathic Pulmonary Fibrosis 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.
In addition to NIH funding, the Cowlin Family Fund at Chicago Community Trust provided financial support for this study.
Zambon donated the NAC and matching placebo; the prednisone, azathioprine, and their matching placebos were purchased using study funds.
Part of the National Institutes of Health, the National Heart, Lung, and Blood Institute (NHLBI) plans, conducts, and
supports research related to the causes, prevention, diagnosis, and treatment of heart, blood vessel, lung, and blood diseases; and sleep
disorders. The Institute also administers national health education campaigns on women and heart disease, healthy weight for children, and
other topics. NHLBI press releases and other materials are available online at
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