Biologic Therapy Failed to Improve Wound Healing in Critical Limb Ischemia in STOP-PAD Trial

The experimental biologic therapy JVS-100 did not improve wound healing when used with revascularization in patients with critical limb ischemia (CLI), according to the STOP-PAD trial. The results were presented by Mehdi H. Shishehbor, DO, MPH, FACC, on Monday, March 12 in a Late-Breaking Clinical Trial session at ACC.18 in Orlando, FL.

The STOP-PAD trial randomly assigned 109 patients with CLI and at least one nonhealing foot wound to low- or high-dose JVS-100 or placebo following successful or attempted revascularization with open bypass grafting or endovascular treatment of below-knee arteries. JVS-100 is a non-viral DNA plasmid encoding human stromal cell-derived factor-1 (SDF-1), which promotes tissue repair by inducing cell survival, endogenous stem cell recruitment and vasculogenesis. JVS-100 was given in two doses – one within 12 days after revascularization and the second three months later.

The primary efficacy endpoint was wound healing, measured by a core lab adjudicated composite score at three and six months after the initial dose. The secondary endpoints were death, amputation, major adverse limb events (MALE) and major adverse cardiovascular events (MACE).

The post-intervention total brachial index (TBI) was 0.26. A total of 10 deaths and six major amputations were reported during the study. Three months after the initial injection, 20 percent of patients in the JVS-100 group and 15 percent of those in the placebo group had undergone amputation. The MALE rate was 14 percent in the JVS-100 group and 9 percent in the placebo group. The wounds grew by ≥25 percent in 30 percent of patients in the JVS-100 group and in 21 percent of those in the placebo group. These differences were not statistically significant. Assessment of blood flow in the smaller arteries during follow-up showed that none of the patients achieved a normal TBI (>0.71) after revascularization or at three months. No significant difference in TBI between the JVS-100 and placebo groups was observed.

Patient outcomes will be assessed for at least 12 months. “We are very much looking forward to the six-month data,” Shishehbor said. “Based on those results, we will determine whether we will investigate this biologic therapy in a longer study, or perhaps consider studying a combination therapy that involves more than one biologic therapy.”

Clinical Topics: Vascular Medicine, Atherosclerotic Disease (CAD/PAD)

Keywords: ACC18, ACC Annual Scientific Session, Aneurysm, Peripheral Arterial Disease, Chemokine CXCL12, Cell Survival, Quality of Life, Ankle Brachial Index, Amputation, Wound Healing, Plasmids, Stem Cells, Biological Therapy, Arteries, DNA

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