New approach to DVT delivers impressive results
A novel way to treat deep vein thrombosis (DVT) that involves injecting the clot-busting agent alteplase (rTPA) directly into the clots shows promise mid-way through a second study of the approach that is using much lower doses of rTPA than the initial pilot.
The first study, reported in the February 2008 issue of Radiology, involved 20 patients with DVT who were given daily 50-mg injections of rTPA for up to four days, as well as blood-thinning therapy. During a three-year follow-up period, none of the patients developed complications from the treatment or experienced a recurrence of DVT.1
Testing new protocol
Even though the results from the pilot were excellent, investigators are testing the approach using a new treatment protocol that uses a dose of rTPA that is five times lower than what was used initially, according to Richard Chang, MD, the developer of the approach. Chang is the chief of the Interventional Radiology Section of the Department of Radiology, Clinical Center, at the National Institutes of Health (NIH).
"When we did the procedure with the higher dose, we did pharmokinetic studies where we followed the amount of rTPA that reaches the circulation," explains Chang. He notes that investigators measured what happens to the natural inhibitor of rTPA in the circulation and watched how much thrombolysis was achieved. "It all showed that probably we were getting most of our effect from a very small dose of rTPA and that we didn't need to use so much," Chang says.
Hurdles remain
Thus far, results from the second study are similar to what investigators observed in the first group of participants, indicating that safer dosages of rTPA can successfully be used to the same effect — at least at this stage of the study.
"The primary reason for safety here is that you must develop a technique that minimizes the total exposure of the systemic circulation to the strong thrombolytic enzymes," Chang emphasizes. He notes that he is able to minimize this exposure by reducing the dosage of rTPA and by minimizing the duration of the drug's circulation in the system.
While the approach shows considerable promise in clearing clots from the smaller veins in the lower leg, larger studies are needed to confirm the early results. Additionally, there are drawbacks that could inhibit adoption of the technique on a large scale. The biggest issue is that finding and accessing these smaller veins with a catheter can take 3-4 hours for the initial treatment.
Chang places the catheter into each of the small calf veins that has a clot and tries to individually address each one of them, which is something that almost no clinicians are doing now, says Suresh Vedantham, MD, an interventional radiologist and an assistant professor of radiology and surgery at Washington University School of Medicine in St. Louis, MO. "Unless you can show a big benefit from it, it will be a hard sell in the long run," Vedantham says. "But I think that the general approach of doing this with once-daily injections — if [Chang] could modify that to make it a little bit more physician friendly — I think it is definitely worth investigating."
Results are impressive
Chang agrees that many interventional radiologists have yet to be convinced that going beyond anti-coagulation therapy to treat DVT in the lower leg is necessary. But he believes it is essential to preventing recurrence and other long-term problems.
"To prevent clotting, you have to have good blood flow throughout all your veins, and if you don't restore your calf veins well, then the flow into the veins above the knee is also reduced and your risk of re-clotting goes up," says Chang.
Furthermore, Chang emphasizes that he and his colleagues have gone a long way toward demonstrating that if you can get thrombolytic agent into all the clots, you can almost restore the system to normal. "We have also been able to figure out what is a reasonable dose, at least for rTPA, but we do need to improve the technique for accessing all the different veins."
Vedantham is impressed that with three-years of follow-up, none of the 20 patients in the initial pilot study has developed post-thrombolytic syndrome, which is the long-term damage that can result from blood clots in the legs. It generally occurs in about half of all DVT patients. Furthermore, he emphasizes that one of the most appealing aspects of Chang's approach is that it could potentially turn what is traditionally an inpatient procedure into an outpatient procedure.
"The idea is that this might convert the treatment into a much more patient-friendly, resource-efficient method, compared to what we have now," Vedantham says.
A novel way to treat deep vein thrombosis (DVT) that involves injecting the clot-busting agent alteplase (rTPA) directly into the clots shows promise mid-way through a second study of the approach that is using much lower doses of rTPA than the initial pilot.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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