Arenas Ivan, Ujueta Francisco, Diaz Denisse, Yates Timothy, Olivieri Brandon, Beasley Robert, Lamas Gervasio
Cardiology, Mount Sinai Medical Center, Miami Beach, USA.
Internal Medicine, Mount Sinai Medical Center, Miami Beach, USA.
Cureus. 2019 Dec 27;11(12):e6477. doi: 10.7759/cureus.6477.
Background In 2015, there were 30.3 million patients with diabetes in the US, including 25.2% of people ages 65 or older and 108,000 hospitalizations for non-traumatic amputations. Severe diabetic limb disease includes critical limb ischemia (CLI ) due to an infrapopliteal disease with foot pain and ischemic ulcerations including gangrene. Environmentally acquired toxic metals, such as lead and cadmium, have been associated with cardiovascular disease. Thus, we designed the present unblinded pilot study to determine whether there was a signal of benefit for edetate disodium-based infusions in patients with critical limb ischemia. Methods This was an open-label pilot study in 10 patients with diabetes and critical limb ischemia. Each patient received up to 50 edetate disodium-based infusions and was assessed for safety, clinical efficacy, metal excretion, and quality of life. The primary endpoint was to assess the effect of edetate disodium-based therapy plus vitamins in patients with diabetes and infra-popliteal peripheral artery disease presenting with severe CLI and determine if there were improvements in vascular flow parameters. Results We enrolled 10 (60% male) predominantly Caucasian (90%) subjects. The mean age was 75.3 (8.0) years. Smoking was reported by 30%. There were 70% with coronary artery disease (30% had prior coronary artery bypass grafting) and 50% had a prior lower-extremity amputation, three having previous minor amputations and two major amputations. There were no major adverse cardiovascular events during the infusion phase through the one-year follow-up. Patients completing 40 infusions demonstrated complete wound healing and improvement in the quality of life. Conclusion Patients with diabetes and CLI treated with a regimen of edetate disodium-based infusions demonstrated a potential signal of benefit and preliminary evidence of safety. The Trial to Assess Chelation Therapy in Critical Limb Ischemia (TACT3a), a randomized double-blind, placebo-controlled clinical trial now in progress, will further test these findings.
背景 2015 年，美国有 3030 万糖尿病患者，其中 65 岁及以上人群占 25.2%，因非创伤性截肢住院的有 108000 人。严重糖尿病肢体疾病包括因腘动脉以下疾病导致的严重肢体缺血（CLI），伴有足部疼痛和缺血性溃疡，包括坏疽。环境中获取的有毒金属，如铅和镉，与心血管疾病有关。因此，我们设计了这项非盲法先导研究，以确定基于依地酸钠的输注对严重肢体缺血患者是否有益。方法 这是一项针对 10 例糖尿病合并严重肢体缺血患者的开放标签先导研究。每位患者接受多达 50 次基于依地酸钠的输注，并评估安全性、临床疗效、金属排泄和生活质量。主要终点是评估基于依地酸钠的治疗加维生素对患有严重 CLI 的糖尿病和腘动脉以下外周动脉疾病患者的效果，并确定血管血流参数是否有改善。结果 我们招募了 10 名（60%为男性）主要为白种人（90%）的受试者。平均年龄为 75.3（8.0）岁。30%的人有吸烟史。70%的人患有冠状动脉疾病（30%曾接受冠状动脉搭桥术），50%的人曾有下肢截肢史，其中 3 人曾接受小截肢，2 人曾接受大截肢。在输注阶段至一年随访期间未发生重大不良心血管事件。完成 40 次输注的患者伤口完全愈合，生活质量得到改善。结论 接受基于依地酸钠输注方案治疗的糖尿病合并 CLI 患者显示出潜在的益处信号和初步的安全性证据。正在进行的一项随机双盲、安慰剂对照临床试验——严重肢体缺血螯合疗法评估试验（TACT3a）将进一步验证这些发现。
