Press Release

FDA: Paclitaxel Device Clinical Trials “May Continue”; Agency is Working to Change Informed Consent Documents and Product Labelling

News Source: Vascular News

Clinical studies of paclitaxel-coated balloons and paclitaxel-eluting stents “may continue and should collected long-term safety (including mortality) and effectiveness data”, says the US Food and Drug Administration (FDA) in a letter to healthcare providers on 7 August. This is due to “the demonstrated short-term benefits of the devices, the limitations of the available data, and uncertainty regarding the long-term benefit-risk profile of paclitaxel-coated devices”.

The letter provides an update on the agency’s stance on the use of paclitaxel devices to treat peripheral arterial disease (PAD) in the femoropopliteal arteries. The FDA say clinical studies investigating these devices in the lower leg “require appropriate informed consent and close safety monitoring to protect enrolled patients”, and confirm they are working with study investigators to modify informed consent documents to include information about the late mortality signal.

The FDA state: “Based on the conclusions of our analysis and recommendations of the advisory panel, the FDA is taking additional steps to address this signal, including working with manufacturers on updates to device labelling and clinical trial informed consent documents to incorporate information about the late mortality signal. The FDA is also continuing to actively work with the manufacturers and investigators on additional clinical evidence development for assessment of the long-term safety of paclitaxel-coated devices.”

Summary of Earlier FDA Statements

In June this year, the agency convened a Circulatory Systems Devices Panel meeting (19–20 June, Washington, DC, USA) on the late mortality safety signal associated with paclitaxel-coated balloons and paclitaxel-eluting stents used to treated PAD in the femoropopliteal arteries.

Following the two-day discussion, which included the presentation of the agency’s own analysis of long-term follow-up data from pivotal premarket randomised trials, an FDA Circulatory System Devices Panel Advisory Committee concluded that there is a “late mortality signal”, as first described in the Journal of the American Heart Association (JAHA) paper authored by Konstantinos Katsanos et al (Patras, Greece) in December 2018.

However, they also concluded that better data collection was necessary going forward, as some data were missing, a small sample size meant there were wide confidence intervals, and there was pooling of studies of different paclitaxel devices that were not intended to be combined. The panel determined that there were not enough data to confirm a class effect, and no consensus was reached on the cause(s) of death.

In their most recent letter to healthcare providers, dated 7 August 2019, the FDA summarise the deductions of the advisory committee back in June: “In the three randomised trials which enrolled a total of 1,090 patients, the crude mortality rate at five years was 19.8% (range 15.9–23.4%) in patients treated with paclitaxel-coated devices compared to 12.7% (range 11.2–14%) in subjects treated with uncoated devices. The relative risk for increased mortality at five years was 1.57 (95% confidence interval 1.16–2.13), which corresponds to a 57% relative increase in mortality in patients treated with paclitaxel-coated devices. A meta-analysis performed by VIVA (Vascular InterVentional Advances) physicians of patient-level data provided by manufacturers reported similar findings with a hazard ratio of 1.38 (95% confidence interval 1.06–1.80). […] The Panel determined, and the FDA concurs, that additional clinical study data are needed to fully evaluate the late mortality signal.”

© FreeLIMS.org. Powered by CloudLIMS.com