Initial findings of an early feasibility trial have demonstrated that the LimFlow System does represent a safe and reproducible method of treating patients with no-option critical limb ischaemia (CLI). The results of PROMISE I, which were described by chief investigator Daniel Clair (University of South Carolina, Columbia, USA) as “very promising”, show the potential of the system for improving wound healing rates and reducing the number of amputations performed.
Presented at the 2019 Vascular Interventional Advances conference (VIVA; 4–7 November, Las Vegas, USA), Clair asserted the possible benefits of LimFlow in “a patient population for whom amputation would otherwise be considered inevitable”. He added: “It is very encouraging to be able to offer hope to patients that cannot be treated with any current technology today.”
Previously, as Clair explained in his presentation, these no-option patients would have received a “dead-end angioplasty” in an effort to revascularise the peroneal artery and promote healing, but the chances of success in this situation are very low. The percutaneous deep vein arterialisation system LimFlow has emerged as an option for said patients, and was investigated in PROMISE 1, a prospective, single-arm study launched in 2017 that was conducted at seven centres in the USA.
“The device itself requires antegrade arterial access on the ipsilateral side and antegrade venous access from below the point of entry into the artery,” said Clair, who described how the system itself operates. “An ultrasound guidance catheter directs a needle to advance into the vein, while a wire advances through the venous system of the foot. Then, an antegrade valvulotome passes over a wire to lyse the valves, before stent grafts are placed to take branches out of the circulatory aspect, allowing for the direction of blood flow into the foot”.
PROMISE 1 aimed to establish the clinical safety of LimFlow—before progression to a pivotal study—and address any operator challenges with the system. Furthermore, the trial sought to determine any patient characteristics and therapeutic parameters which might impact the performance of LimFlow. Findings of the trial, as Clair outlined, will support the optimisation of operator technique, as well as the development of subsequent protocols such as patient screening, wound analysis and patient follow-up.
Key endpoints listed for the study included the primary safety endpoint of amputation free survival at 30 days, in addition to secondary endpoints such as amputation free survival at six months, procedural and technical success, wound healing, and patency. Only patients of Rutherford 5 or Rutherford 6 classification—with no-option critical limb-threatening ischaemia (CLTI)—were included in the study, whereas those with of a life expectancy of less than a year, or on dialysis, were excluded. A critical review of the patients by an independent committee was also conducted to ensure that patients enrolled had no other option.
Of the patients who were included, they had an average age of 71 years and 66% were male. Moreover, a significant proportion also suffered from comorbidities such as diabetes (68%), hypertension (88%) and renal insufficiency (34%), “although end-stage renal disease was an exclusion characteristic,” emphasised Clair.
In terms of the primary endpoint, it was found that the amputation-free survival rate among these patients after six months was 74%. Commenting on these results, Clair said: “These are all patients who were heading, in my view, to amputation. With the morality rate among this population, the real issue here is keeping these patients alive with their limbs and that is what this device is designed to do.”
The area of the patients’ wounds was also reviewed by a core lab to ensure accurate presentation, and it was found that while the average size of the wounds may increase initially, which “may be related to the fact that either a toe amputation or trans metatarsal amputation was done in order to remove necrotic tissue”, it was noticeable over time that the wounds actually do go on to heal.
Clair continued: “I think it is critical to understand that even in this setting, wounds do not heal within a month; they take a lot of time and attention, which means follow-up is critical for these patients.” At nine months, 62% of the patients’ wounds had healed, while 100% had either healed or were healing.
Reflecting on lessons learned from PROMISE I, the speaker concluded: “Obviously for patients who are too far gone for arterial reconstruction, this is not a magic wand that we can use for everyone, and multidisciplinary wound care is critical. Minor amputations need to be managed, allowing for some swelling that is more than what you might see in a typical arterial revascularisation, and you need to closely monitor the fistula to ensure you have good flow through here during the early period of time, which may necessitate interval interventions.”