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STOP-PAD: Biologic therapy for CLI remains ineffective at 6 months
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LAS VEGAS — An experimental biologic treatment did not improve wound healing or clinical outcomes in patients with critical limb ischemia, according to 6-month data from the STOP-PAD trial presented at VIVA 18.
The phase 2, double-blind, randomized, placebo-controlled STOP-PAD trial evaluated the safety and efficacy of JVS-100 (Juventas Therapeutics), 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.
As Cardiology Today’s Intervention previously reported, the therapy did not improve wound healing or major adverse limb events at 3 months in 109 patients who underwent lower-extremity revascularization. Cardiology Today’s Intervention Editorial Board Member Mehdi H. Shishehbor, DO, PhD, MPH, director of the cardiovascular interventional center and co-director of the vascular center at University Hospitals Harrington Heart and Vascular, reported the 6-month results here.
“After 20 years of research, we are left with bypass and angioplasty alone to treat CLI,” Shishehbor said during a presentation. “However, only 20% to 30% of wounds heal within 3 months, and wounds are associated with depression, poor quality of life, increased health care costs, amputations and death. Revascularization improves macrovascular perfusion, but there is seldom, if ever, a normalization of microvascular perfusion. How can we improve both?”
The therapy encodes stromal cell-derived factor-1, which “activates endogenous regenerative repair pathways, promotes new blood vessel growth, prevents cell death and causes remodeling of scar tissue,” he said.
Among the study population, 34 were assigned placebo (mean age, 71 years; 68% men), 34 were assigned an 8-mg injection of JVS-100 (mean age, 68 years; 59% men) and 36 were assigned a 16-mg injection of JVS-100 (mean age, 72 years; 69% men).
At 6 months, the wound healing score did not differ between the groups (P = .95), Shishehbor said, noting that in all three groups, more than 30% of patients had their wounds worsen in size by 25% or more (placebo group, 42%; both JVS-100 groups, 37%).
Any amputation occurred in 24% of the placebo and 8-mg JVS-100 groups and 22% of the 16-mg JVS-100 group; major amputations occurred in 3% of the placebo and 8-mg JVS-100 groups and 6% of the 16-mg JVS-100 group; and major adverse limb events occurred in 24% of the placebo group, 29% of the 8-mg JVS-100 group and 11% of the 16-mg JVS-100 group, according to the researchers.
Six-month mortality rates were 9% in the placebo group, 6% in the 8-mg JVS-100 group and 3% in the 16-mg JVS-100 group.
“Only 35% of wounds healed within 6 months despite advanced revascularization and vigorous follow-up,” Shishehbor said during the presentation. “More than one-third of the wounds actually got bigger over 6 months. Future biologic therapies may require addressing multiple pathways.” – by Erik Swain
Reference:
Shishehbor MH, et al. Late-Breaking Clinical Trials. Presented at: VIVA 18; Nov. 5-8, 2018; Las Vegas.
Disclosure: The study was funded by Juventas Therapeutics. Shishehbor reports he received honoraria from Abbott Vascular and Medtronic and consulted for Abbott Vascular, Boston Scientific, Medtronic, Philips and Terumo.