This article is more than 5 years old. Information may no longer be current.
STOP-PAD: Biologic therapy fails to improve outcomes in CLI
ORLANDO, Fla. — An experimental biologic treatment did not improve wound healing or major adverse limb event rates in patients with critical limb ischemia at 3 months, new data indicate.
Revascularization, which is currently the mainstay of treatment for CLI, only addresses macrovascular perfusion and seldom fails to normalize microvascular perfusion, according to Mehdi Shishehbor, DO, PhD, MPH, director of the cardiovascular interventional center and co-director of the vascular center at University Hospitals Harrington Heart and Vascular, and a Cardiology Today’s Intervention Editorial Board Member.
“The question is: Can we combine macrovascular revascularization with microvascular therapy to improve wound healing in patients with CLI?” he said during a presentation at the American College of Cardiology Scientific Session.
Shishehbor and colleagues conducted the phase 2, double-blind, randomized, placebo-controlled STOP-PAD trial to evaluate the safety and efficacy of JVS-100 (Juventas)— a biologic therapy that delivers DNA that encodes proteins involved in the production of blood vessels — as an adjunct to revascularization in patients with Rutherford class 5 or 6 CLI.
One hundred nine patients who underwent lower-extremity revascularization at 21 centers were randomly assigned to placebo (n = 34), an 8-mg injection of JVS-100 (n = 34) or a 16-mg injection of JVS-100 (n = 36).
Shishehbor said JVS-100 did not meet the primary endpoint of wound healing in this patient population, with complete wound healing occurring in only 26.5% of the placebo group, 26.5% of the JVS-100 8-mg group and 25% of the JVS-100 16-mg group at 3 months (P = .93).
He said wounds progressed more than 25% in 20.6% of patients in the placebo group, 38.2% in the 8-mg group and 22.2% in the 16-mg group.
Furthermore, 14.7% of the placebo group, 20.6% of the 8-mg group and 19.4% of the 16-mg group underwent amputation. Rates of major adverse limb events — a composite of major amputations plus clinically driven target lesion revascularization — were 8.8%, 20% and 8.3%, respectively. All-cause mortality rates were 2.9%, 5.9% and 0%, respectively.
These findings were not statistically significant, but the study was not powered to detect differences in these endpoints, Shishehbor said.
Many of the study patients had multiple comorbidities, with more than 80% having diabetes and 10% having end-stage renal disease. Ten percent also had ulcers on the heel, which are the most difficult to treat, according to Shishehbor. Despite aggressive revascularization, all patients had low hemodynamics at baseline.
The study had several limitations, Shishehbor noted, including its short duration. Additionally, an angiosome-based approach was not mandated and wound care was not standardized. The optimal route and location to deliver JVS-100 also may not be ideal, he said, and toe-brachial index may not be sensitive enough to assess microcirculation.
“Adjunctive injection of JVS-100 failed to impact wound healing or rates of major adverse limb events in patients with Rutherford class 5 or 6 CLI,” Shishehbor said. “We will anxiously await 6-month results, but future biologic therapies may require addressing multiple sites and pathways.” – by Melissa Foster
Reference:
Shishehbor M, et al. Late-Breaking Clinical Trials: Interventional. Presented at: American College of Cardiology Scientific Session; March 10-12, 2018; Orlando, Fla.
Disclosure: The study was sponsored by Juventas. Shishehbor reports he has received consultant fees or honoraria from Abbott.