Six-month outcomes of a multicentre randomised controlled trial using the Lutonix 014 drug-coated balloon (BD; DCB) has demonstrated the DCB is safe to use in peripheral lower limbs, below the knee. The primary safety endpoint of freedom from major adverse limb events and all-cause perioperative death at 30 days was met, and a Kaplan-Meier analysis indicated “no significant difference” in safety between the DCB and the plain percutaneous transluminal angioplasty (PTA) arms of the study.
The data were presented at the Vascular Interventional Advances annual conference (VIVA; 5–8 November, Las Vegas, USA) by Jihad Mustapha of Advanced Cardiac and Vascular Amputation Centers, Grand Rapids, USA. Mustapha said the study provide the “largest randomised controlled dataset on DCB versus PTA that is available to us as of today”, adding, “This is the first level 1 endovascular therapy treatment involving a multicentre, blinded randomised BTK trial.”
The clinical study is a prospective, global, multicentre, randomised, controlled trial comparing the Lutonix 014 DCB to standard angioplasty for the treatment of narrowed or obstructed arteries below the knee. The study used both proportional/binary and Kaplan Meier analyses to assess safety and efficacy. The primary safety endpoint—freedom from composite all-cause death, above ankle amputation or major reintervention of the treated limb through 30 days—was met showing statistically significant safety equivalence between the Lutonix 014 DCB and standard PTA catheter, in both the proportional/binary and Kaplan Meier analyses.
Mustapha expressed his hopes for the impact of these data, and excitement about the outcomes, stating: “The six-month clinical data from the Lutonix BTK trial represent the beginning of a paradigm shift in the treatment of patients with critical limb ischaemia (CLI). The initial results are extremely encouraging and give new hope to patients with CLI.”
“Previously published DCB BTK trials have generated concern,” Mustapha said, “regarding amputation rates with DCB use—this is why we looked beyond 30 days, and saw no difference in primary safety at six months between DCB and PTA. The numbers were very close: 97% versus 95%.”
The primary efficacy endpoint was assessed using a composite measurement of freedom from target limb occlusion, above ankle amputation, and clinically driven target lesion revascularisation, to define primary patency. Proportional/binary analysis revealed an improvement in primary efficacy of 10.2% (DCB: 73.7% and PTA: 63.5%, p=0.0273, not-significant) at six months. The more commonly used Kaplan Meier analysis of the primary efficacy endpoint demonstrated a significant difference of 14.6% (DCB: 85.3%, PTA: 70.7%, p<0.001). Additional analyses are planned for 12-, 24- and 36-month follow-ups.
The trial included 442 participants of which 91% had CLI. “Patients with BTK CLI are the most complex subset of peripheral arterial disease in general,” Mustapha said, highlighting the high rates of amputation estimated at around 25–33%, and an approximate US$95 billion cost in the USA per year to treat this patient population.
The amputation rate specific to each arm of the study was not available at the time of presenting, however Mustapha emphasised the notably low overall rate of amputation, comparing the 3.8% figure at six months to double-digit rates in previous trials. “We did not see any increased rate of amputation in the DCB arm,” Mustapha clarified, “but in general actually the number of amputations was less than 4% in the entire cohort—PTA and DCB.”
At baseline, 71% of all patients enrolled had diabetes, 92% had hypertension and close to 60% of patients were smokers. Within the 91% with CLI, the majority were Rutherford category four and five. Addressing baseline demographic risk factors, Mustapha noted that Rutherford categories were balanced across both arms, however the DCB arm had 40% more TASC C and D lesions than the PTA group, and mean lesion length was longer. “The DCB group had more severe lesions concerning calcification and chronic total occlusions with 40.4% more than in PTA.”
Mustapha suggested it is important to note that this is the first global randomised trial to demonstrate safety of a DCB in BTK use, as “generally, in this very sick patient population, with an extremely challenging vascular bed, it is important to put this safety issue to rest: to know that you can use DCB in these severely diseased patients.”
The device has been submitted to the US Food and Drug Administration (FDA) for this indication.