Both Medtronic and Cook Medical have issued corrections to published data regarding the safety of their paclitaxel-coated devices. While Medtronic have revised IN-PACT post-market study data due to a “programming error,” Cook Medical have noted a mistake made during data publication, and that two mortality figures were “inadvertently reversed”. Both companies had recently emphasised the gravity of published data on the safety of their devices, following the December 2018 meta-analysis of Katsanos et al, which associated paclitaxel-coated devices with a higher risk of death.
In a statement, Medtronic said that the company “recently became aware of a programming error in the clinical data reporting isolated to the two- and three-year follow-up periods in our IN.PACT Global post-market study, part of the IN.PACT Admiral clinical programme for the treatment of femoropopliteal artery disease. Preliminary results of this study were first released at the Leipzig Interventional Course (LINC) and Medtronic issued a press release summarising the results on January 22, 2019.”
According to Medtronic, due to a programming error, mortality data were inadvertently omitted from the summary tables included in the statistical analysis. These deaths were, however, previously included and reported in Medtronic’s database, captured in the appropriate study exit forms and adjudicated by an independent clinical events committee. In addition, the company stated, the deaths were previously recorded in Medtronic’s complaint system, and MDR/Vigilance reporting has been completed in compliance with the company’s Quality Systems, which are governed by external regulatory requirements.
Immediately upon learning of this error, Medtronic notified the FDA and the study authors. The company stated that while a component of the recent patient-level meta-analysis will need to be updated, it has found the revised analysis still supports earlier conclusions that: there was no statistically significant difference in all-cause mortality between the IN.PACT Admiral drug-coated balloon (DCB) and plain balloon angioplasty at five years; there is no correlation between paclitaxel dosing and long-term survival in the studied population; and, there was no difference in mean nominal dose of paclitaxel between overall survival in patients treated with DCB and those who died.
The data update impacts the publication of the IN.PACT Global two-year data in the Journal of the American College of Cardiology: Cardiovascular Interventions (JACC CI), and the IN.PACT paclitaxel safety analysis, which is in print with the Journal of the American College of Cardiology (JACC). Medtronic has confirmed no other IN.PACT studies are affected by this error, and it is important to note this discrepancy is limited to deaths after the one-year time-point.
Respecting the scientific process, the revised analysis is currently moving through the appropriate peer-review with the study authors and JACC so the manuscripts can be appropriately corrected.
Medtronic also notes a related study published on February 12, 2019 in JAMA Cardiology, “Association of Survival With Femoropopliteal Artery Revascularisation With Drug-Coated Devices.” The study authors concluded: “In this large nationwide analysis of Centers for Medicare and Medicaid Services beneficiaries, there was no evidence of increased all-cause mortality following femoropopliteal artery revascularization with drug-coated devices compared with non-drug-coated devices.”
Zilver PTX mortality data
The authors of the paper by Dake et al, “Durable clinical effectiveness with paclitaxel-eluting stents in the femoropopliteal artery 5-year results of the Zilver PTX randomised trial,” have issued corrections to the text published in 2016 in Circulation.
According to Circulation, “when high-resolution files were requested during production, an incorrect version of Figure 1 was mistakenly provided. Subsequently, the published version of the flow chart in Figure 1 contained incorrect numbers. The authors now provide the corrected version of Figure 1.”
Additionally, the journal informed, the following sentence from the ‘Safety’ section was incorrect: “The five-year all-cause mortality rate was 13.6% (10.2% for the primary DES group and 16.9% for the PTA group, p=0.03), and no deaths were adjudicated as procedure or device related.” The authors regret that the numbers for the two groups were inadvertently reversed. The sentence should be read: “The five-year all-cause mortality rate was 13.6% (16.9% for the primary DES group and 10.2% for the PTA group, p=0.03), and no deaths were adjudicated as procedure or device related.”
These corrections have been made to the current online version of the article.