An unplanned interim analysis published in the New England Journal of Medicine of an open-label, registry-based clinical trial has found no link between paclitaxel-coated devices and increased mortality.
Researchers conducted the unplanned review in response to a 2018 meta-analysis that found mortality at two years was significantly higher in patients treated with devices coated in paclitaxel. The finding has since been called into question by other studies, but led to increased FDA oversight over the devices.
The registry study adds to the evidence in support of the continued use of paclitaxel-coated devices. Across one to four years of follow-up, mortality was almost identical in patients who received uncoated or coated devices for symptomatic peripheral artery disease.
The data add to evidence accumulating since the 2018 meta-analysis led the FDA to take a closer look at the devices, hold an advisory meeting examining the mortality signal and ultimately add new warning labels, putting pressure on medtechs like Boston Scientific and Medtronic.
The latest comes from the Swedish Drug-elution Trial in Peripheral Arterial Disease, after recruitment in the clinical trial stopped in response to the 2018 meta-analysis. In light of the potential mortality risk, the data and safety monitoring committee recommended an unplanned interim assessment of the data.
Researchers published the findings of that assessment in the New England Journal of Medicine on Wednesday. After a mean follow-up of 2.5 years, the all-cause mortality rate in the paclitaxel cohort was 25.5%, versus 24.6% in the uncoated arm.
Similarly close results were seen at specific time points and in particular populations of patients. One-year mortality was 10.2% in the paclitaxel group and 9.9% in the uncoated cohort. In patients with chronic limb-threatening ischemia, the all-cause mortality rates across the whole study were 33.4% in the paclitaxel arm and 33.1% in the uncoated group.
The mortality rates in patients with intermittent leg cramping were similar, too, although the authors of the NEJM paper note the small number of deaths in that population makes it hard to draw firm conclusions. It is theoretically possible there may be a difference in mortality in that subgroup but the available data suggests paclitaxel-coated devices are as safe as their uncoated counterparts.
Despite that caveat, the interim analysis gave the researchers the confidence to resume recruitment in the clinical trial. The resumption of the study, designed to show if coating devices in the drug prevents amputations and improves quality of life, is part of a broader return to the use of the products in response to studies into mortality.
Boston Scientific sees the recovery of demand for paclitaxel devices as a tailwind after the franchise was put under pressure by the mortality concerns. The recovery is built on data published by Boston Scientific and rivals such as Cook Medical, Medtronic and Philips, as well as by analyses of Optum Medicare Advantage patients and other recipients of paclitaxel-coated devices. Yet, companies are still contending with the impact of labels revised in light of the 2018 meta-analysis.