A percutaneous procedure to avert amputation in patients with chronic limb-threatening ischemia.

Patients who are facing foot or below-the-knee amputation due to chronic limb-threatening ischemia (CLTI) may soon be offered a minimally invasive way to retain their limb and assure continued ambulation. This percutaneous procedure, developed by LimFlow, with the clinical guidance of vascular surgeon Daniel G. Clair, M.D., is currently in phase II (PROMISE II) trials. 

Clair, who is chair of the Department of Vascular Surgery at Vanderbilt University Medical Center, is the global primary investigator on the trials, and one of the first three surgeons in the country to use the technology. Vanderbilt has been the site of six of the 105 procedures to date in Phase II of the PROMISE trials, and Clair hopes to continue to perform the procedures via an FDA continued access extension.

“Among the 32 phase I patients, technical success was achieved in 31 procedures,” Clair said. “Twenty-one patients remained alive and amputation-free at six months, and this remained unchanged at 12 months. These same patients, in about 90 percent of the cases, would have ended up with a foot or below-the-knee amputation without this option.”

From Hopeless to Healing

Factors leading to CLTI commonly include some combination of factors, including age, lifestyle or chronic diabetes that have led to degeneration of the cardiovascular structure in one or both lower limbs. These conditions go unexamined by angiogram in the majority of patients facing a major amputation, and more than half have received no other interventions attempting to restore blood flow.

“When these patients’ conditions are not addressed early enough, a normal arterial bypass procedure is no longer an option, because the foot lacks an arterial structure to connect with,” Clair said. “It becomes what we refer to as a ‘desert foot,’ lacking the fluids it needs. For these patients, the percutaneous option is critical to avoid the high risks associated with open surgery.”

Eligibility for the arterialization procedure extends to the 20 percent of patients with critical limb ischemia who are no longer candidates for open revascularization surgery (bypass) or angioplasty. However, Clair says, this technique may lead to further enhancements in standard therapies.

How to Arterialize a Vein

This arterialization technology comprises a catheter-based system of wires, stents and a valvulotome to arterialize one of the lower leg’s six to nine veins. To perform the procedure, the interventionalist enters the leg through both the patient’s groin and foot, creating a connection between the two in the calf. Here, a crossover occurs from an artery to a vein.

“We’re reversing the flow through one of the veins, allowing restoration of oxygen delivery to the foot,” Clair explained.

Meanwhile, the lower leg’s additional veins carry on with the job of reoxygenating the blood by returning it to the pumping heart.

“Based on these studies, if the patient makes it beyond the first three months with their limb, they won’t lose it.”

Crossings in Phase I were predominantly performed from the tibioperoneal trunk or posterior tibial artery to the posterior tibial vein. A small number were performed from the anterior tibial artery to the anterior tibial vein, or from the popliteal artery to the popliteal vein.

The procedure typically takes between five and seven hours, and recovery time is one or two nights in the hospital. Patients may walk as soon as a day or two later, but the puncture wound on the bottom of the foot can delay this in some.

“Of the 17 patients who had reinterventions for occlusion in the first trial, 16 were performed because of unhealed wounds “They need to heal from the inside out, which can seem counterintuitive. When handled properly, though, we see dramatic healing in these patients by six to 12 months, which is very difficult to achieve.”

PROMISE Phase I Outcomes

The phase I procedural success rate was 75 percent, as measured by the outcome of reperfusion and retention of the “desert foot.”

“This procedure takes about six to 10 weeks to work, but once it works, it’s unbelievable,” Clair said.  

“Based on these studies, if the patient makes it beyond the first three months with their limb, they won’t lose it.”

Phase II of the PROMISE trials includes 105 more patients whose angiograms demonstrate no option for standard revascularization. Trial results will be reported as soon as six months from now, and the procedure may be FDA-approved as soon as mid- to late-2023.

Mysterious Mechanics

“This procedure creates a pathway to some of the arterioles in the foot and increases pressures in the venous system. The mechanism is not entirely clear and likely varies among individuals,” Clair explained, “but we suspect a host of circulatory changes take place to enable the perfusion.”

Perfusing the toes, however, remains a largely unmet challenge. While this procedure prevents amputation of the foot, about a third of the patients still may require a transmetatarsal amputation of some or all toes.

“Currently, we don’t have a valvulotome that would fit into veins as small as those in the toes,” Clair said. “But we have plans to tackle arterializing toes as well. That would be another huge advance.”

About the Expert

Daniel G. Clair, M.D.

Daniel G. Clair, M.D., is a professor and chair of the Department of Vascular Surgery at Vanderbilt University Medical Center and a world-renowned leader, innovator, and pioneer in minimally invasive vascular techniques. His research interests focus on clinical trials of new, innovative vascular therapies and devices. His clinical and research goals include reducing the impact of vascular procedures on a fragile set of patients.