A researcher from the University of Nebraska Medical Center has determined
that a widely used drug for heart attacks is effective in restoring function
in catheters blocked by blood clots, a common medical problem that occurs
in about a million patients every year.
William Haire, M.D., and colleagues from 25 other centers nationwide
found that recombinant tissue plasminogen activator (rt-PA), also known
under the trade name Activase (Alteplase, recombinant), successfully dissolves
blood clots that block central venous access devices called catheters.
A catheter is a thin, silicon rubber tube that is surgically inserted into
large veins such as the jugular (in the neck), femoral (in the leg) or
subclavian vein (in the chest).
Dr. Haire will present his findings from the Cardiovascular Thrombolytic
to Open Occluded Lines (COOL) study Jan. 25 at the International Symposium
for Endovascular Therapy in Miami, Fla. Genentech, Inc., maker of the Activase,
funded the study.
The findings about the drugs effectiveness are important because surgery
currently is one of the few options for restoring flow to a clot-blocked
catheter. Urokinase, the only other drug used for this purpose, was withdrawn
from the market in 1999, creating a major problem for patients and practitioners.
About 5 million patients a year receive intravenous drug medication
through catheters for conditions including cancer, intestinal disease and
those who need long-term, high dose antibiotics. Catheter blockages prevent
patients from getting lifesaving medications and also prevent the drawing
of blood for diagnostic tests. Depending on medical needs, catheters can
be worn for short periods of time or up to several years.
It is estimated about 25 percent of patients will experience blocked
catheters. About 60 percent of those patients have blockages that involve
clots, Dr. Haire said. The other 40 percent are due to mechanical problems
such as kinks in the catheter.
Clots typically develop over time when fibrin, a naturally-occurring
substance that promotes blood coagulation, builds up within the body, near
the tip or along the catheter.
Blockages prevent aggressive, livesaving treatment from being given.
Without, in essence a spigot or faucet, aggressive life-saving treatments
simply couldnt be given, said Dr. Haire, UNMC professor of internal medicine
who specializes in hematology. Furthermore, surgery to remove a catheter
and install a new one is not a favorable option, especially for very sick
patients undergoing bone marrow transplants. Any surgical procedure poses
a significant health risk.
It isnt practical to use the patients own veins and puncture a vein
every time you need to give medication or withdraw blood for diagnostic
purposes. This damages the veins to the point where there may be no usable
veins in most people after a few weeks of therapy, he said.
Dr. Haire, who specializes in blot clots as well as catheter complications,
has published 30 articles on the subjects over the last 15 years, including
two in the New England Journal of Medicine and the Journal of the American
Medical Association.
The six-month COOL study was completed in May 2000. A total of 150 patients
with blocked catheters were enrolled in the randomized, double-blind study
to find out if Alteplase was effective in restoring function to catheters
blocked by clots.
Patients were separated into two groups. For ethical reasons, the study
was designed so all patients ultimately would receive Alteplase for their
blocked catheter.
In the control group, patients were given one dose of placebo a saline
solution — in their catheter. If catheter function was not restored, patients
then received one, 2 milligram dose of Alteplase. If catheter function
was not restored, patients then received a second dose. In this group,
researchers found 17.1 percent of the patients had their catheters working
after the placebo. But after one or two doses of drug, catheter function
was restored in 90 percent of patients.
We think the placebo worked in 17 percent of patients because the catheter
tip may have become kinked inside the vessel and it just straightened out
on its own. Or perhaps it was because we were injecting something, Dr.
Haire said.
In the other control group, patients first received a 2 milligram dose
of Alteplase, followed by another dose if the catheter remained blocked.
In this group, researchers found after just one dose of the drug, 73.9
percent of the patients catheters worked. Those who still had blockage
were given a second dose, restoring catheter function to 90 percent.
No serious drug-related adverse events were observed as a result of
treatment and there were no cases of intracranial hemorrhage, embolism
or serious drug-related reactions.
While a few patients who first received the placebo in this study did
have their catheters cleared, many more patients achieved full catheter
function with Alteplase, demonstrating the drug is vastly superior to placebo,
Dr. Haire said.
The importance of finding ways to dissolve clots caused by catheter
placement became evident when catheters came into widespread medical use
in the late 1970s and early 1980s. A variety of therapies were beginning
to be used for treatment of various types of cancers that all required
medications, transfusions and frequent blood draws, for treatments lasting
several weeks or months.
Dr. Haire has been working with Genentech since 1993 to conduct research
on Alteplases effectiveness in clearing clot-obstructed catheters. Based
on the COOL effectiveness study, another study has been conducted in 1,000
patients to determine the safety of the drug. Those results are expected
soon, Dr. Haire said.