Unprecedented PRESERVE IVC Filter Study Unites Surgeons, Interventionalists, Manufacturers, And The FDA

An unprecedented clinical trial called PRESERVE is bringing together the Society of Interventional Radiology, the Society for Vascular Surgery, major manufacturers of inferior vena cava filters, and the FDA to answer questions about how the filter might best fit into modern medicine.

Many fundamental questions surround the use of inferior vena cava filters for the prevention of pulmonary embolism. What is the true incidence of pulmonary emboli? How well do filters prevent pulmonary embolisms? Which patients should get them? How many filters are retrieved and how many are left behind in the body? What are the complications with retrieving them and what are the complications with leaving them in the body permanently? Such fundamental gaps in understanding seem surprising for a 30-year-old product category (the Greenfield filter from Boston Scientific Corp. was introduced in 1973) with sales of approximately $310 million in 2012, but it has grown up without accumulating the randomized, controlled clinical trial data that could answer these and other questions about the use of IVC filters.

Clinicians, manufacturers, and the FDA hope to remedy that lack of clinical data with the upcoming PRESERVE study, which stands for “Predicting the Safety and Effectiveness of Inferior Vena Cava Filters.” Details of the five-year study, which will be a postmarket investigational-device exemption (IDE) study including FDA-cleared devices, are being finalized, but the massive undertaking will enroll approximately 2,100 people at some 60 centers across the country. The study is “groundbreaking,” says interventional radiologist Matthew S. Johnson, MD, professor of radiology and surgery at Indiana University’s School of Medicine and principal investigator, because it unites the two different physicians groups that place the bulk of IVC filters – interventional radiologists and vascular surgeons – seven manufacturers representing 95% of the current IVC filter market, and the FDA. These groups share the goal of answering questions about the safety and efficacy of filters to determine their appropriate use in the treatment of patients. David Gillespie, MD, chief of the division of vascular surgery at Southcoast Health Systems in New Bedford, MA, and the study’s co-principal investigator says, “We hope to provide a real-world snapshot of what is going on.”

The IVC Filter Study Group Foundation that joins together the Society of Interventional Radiology (SIR) and the Society for Vascular Surgery (SVS) was formed as a response to the FDA’s concern about the increasing volume of IVC filter placements in light of complications that were starting to become apparent. The agency outlined its concerns in a medical alert issued in August 2010 to the physicians who treat patients who get IVC filters.

Between 2005 and 2010 the FDA had received reports of more than 900 adverse events related to device migration, embolizations of components of the devices, perforations of the inferior vena cava, and filter fracture, calling into question the risk/benefit profile of filter placement with respect to various types of patients.

Off-Label Use Concerning

Although the FDA’s labeling for IVC filters covers patients with recurrent pulmonary embolism in certain situations, in practice filters are used for prophylaxis during particular types of surgeries and in many other cases. Notes Gillespie, “Right now the placement of IVC filters exceeds the disease rate, and that’s never good. By that I mean that most of them are being placed for prophylactic reasons, but we don’t have a good handle on the exact reasons people are placing them.” Doctors are trying to protect patients, he says, “but that comes with the assumption that all filters placed are benign. That may be true for 95% of them, but even with a good safety profile, when we’re exponentially increasing the number of filters we’re putting in, if 5% of patients have problems, that’s a large number.”

Johnson notes that it is difficult to evaluate the effectiveness of strategies to prevent pulmonary emboli, because “we don’t know the true incidence of pulmonary emboli, and we don’t know the impact from them. I think it is underestimated how many people are injured or die from pulmonary emboli, and when you don’t know the denominator, it is very difficult to assess the numerator.”

Significant Upside for Manufacturers

Now, with PRESERVE, the hope is to get a clear picture of the risks and benefits of IVC filters in the patients in whom they are being used. Johnson notes that randomized, controlled clinical data are

sorely lacking in the field. There is only one such study, PREPIC, begun in France in 1998, which randomized 400 patients with proximal deep vein thrombosis to receive a filter or not, and which found, at the end of eight years, that permanent vena cava filters reduced the incidence of pulmonary embolism, but increased rates of deep vein thrombosis. Johnson doesn’t believe the PREPIC study is relevant. “It contained numerous filters in a population that American doctors don’t tend to put filters in, and all of the patients were anticoagulated. In the US, we don’t put filters in people who can be anticoagulated.”

Discussions of IVC filters tend to lump them together as a class, but Johnson notes that there are more than eight different manufacturers and many different types of devices, with different amounts of data on each one. “It has been difficult to compare complications, since data have not been collected the same way.” In the PRESERVE study, he says, everyone will be subject to the same definitions. “It will assess the performance of IVC filters as a class, but allow comparisons of different devices.” Gillespie says, “We want to know how well filters prevent symptomatic or fatal PE’s, if one filter does it better than another, and which filters, if any, have significant complications.”

PRESERVE is an expensive undertaking, funded by the participating device manufacturers, but the study designers aim to make it as affordable as possible. “It is almost standard of care. The extra costs the companies will have to pay will include demographic data accrual and the non-standard-of-care imaging, which is an abdominal X-ray at three months, and a CT scan of the abdomen at the level of the filter at one and two years,” Johnson explains.

Johnson estimates that the study will begin by spring of 2014 if not sooner.

Is there a risk for manufacturers that the study could ultimately undercut the use of IVC filters? Johnson doesn’t think so. “I truly believe IVC filters are of value. They are clinically effective; otherwise, I wouldn’t be putting them in my patients.” There is significant upside for manufacturers, not only in creating clear guidelines for IVC filter usage, but in potentially opening up new world markets. “There are 200,000 filters sold in the world, most of them in the US. The rest of the world is still operating on the PREPIC data, which doesn’t say that filters are good.” Johnson asks us to look forward six years. “I think PRESERVE will demonstrate safety and efficacy in people who have a clot. Imagine that we have a massive, multi-society study, supported by the corporations and the FDA working together, that says IVC filters are safe and effective. Now look at China. There are patients there who aren’t getting filters right now.” The US clearly thinks these devices are of value. “It’s the rest of the world that needs to be convinced, and there is a tremendous number of patients who would benefit from appropriate treatment.”