Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study.
Rationale and design of the granulocyte-macrophage colony stimulating factor in peripheral arterial disease (GPAD-3) study.
复制标题
外周动脉疾病中粒细胞-巨噬细胞集落刺激因子 (GPAD-3) 研究的基本原理和设计。
DOI：
10.1016/j.cct.2020.105975
复制
发表时间：
2020
影响因子：
2.2
通讯作者：
Wells,Brya
中科院分区：
文献类型：
--
作者：
Mehta,Anurag;Mavromatis,Kreton;Ko,Yi-An;Rogers,StevenC;Dhindsa,DevinderS;Goodwin,Cydney;Patel,Risha;Martini,MohammadA;Prasad,Mahadev;Mokhtari,Ali;Hesaroieh,IrajG;Frohwein,StephenC;Kutner,MichaelH;Harzand,Arash;Wells,Brya
背景：下肢外周动脉疾病(PAD)是一个公共卫生问题，尽管进行了适当的内科和/或外科治疗，但许多PAD患者仍会出现跛行。使用粒细胞巨噬细胞集落刺激因子(GM-CSF)动员内源性祖细胞是一种新的治疗方案，在实验模型和I/IIA期临床试验中显示出良好的效果。GPAD-3试验将研究每隔3个月连续两次给予GM-CSF改善下肢PAD患者跛行的效果。方法我们计划在这项正在进行的随机、双盲、安慰剂对照的IIB期试验中招募176名患者。在筛选纳入和排除标准后，符合条件的受试者将经历为期4周的筛选阶段，在此阶段，他们每周进行三次皮下安慰剂注射，每天至少步行三次，直到出现跛行。筛查阶段结束后，符合条件的受试者接受基线测试，并以2：1的随机比例接受500g/天的GM-μ皮下注射，每周三次，连续三周或安慰剂注射。3个月后，进行后续终点测试，GM-CSF组的受试者接受为期三周的第二次药物注射，而安慰剂组的受试者接受匹配的安慰剂注射。所有参与者在6个月和9个月的随访中接受终点测试。主要终点是基线和6个月随访期间6分钟步行距离的变化。结论GPAD-3探索了一种新的方法，以满足对可缓解下肢垫患者症状的替代疗法的需求。如果成功，这项研究将为关键的第三阶段试验铺平道路。
BackgroundLower extremity peripheral arterial disease (PAD) is a public health problem and many patients with PAD experience claudication despite adequate medical and/or surgical management. Mobilization of endogenous progenitor cells using Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) is a novel therapeutic option that has shown promising results in experimental models and phase I/IIA clinical trials. The GPAD-3 trial will study the effect of two successive administrations of GM-CSF at 3-month interval for improving claudication among patients with lower extremity PAD.MethodsWe plan to recruit 176 patients in this ongoing randomized, double-blind, placebo-controlled Phase IIB trial. After screening for inclusion and exclusion criteria, eligible subjects undergo a 4-week screening phase where they perform subcutaneous placebo injections thrice weekly and walk at least three times a day until they develop claudication. After the screening phase, eligible subjects undergo baseline testing and are randomized 2:1 to receive 500 μg/day of GM-CSF subcutaneously thrice weekly for three weeks or placebo injections. After 3 months, follow-up endpoint testing is performed and subjects in the GM-CSF group receive the second administration of the drug for three weeks while subjects in placebo group receive matching placebo injections. All participants undergo endpoint testing at six-month and nine-month follow-up. The primary endpoint is change in 6-min walk distance between baseline and 6-month follow-up.ConclusionGPAD-3 explores a novel approach to address the need for alternative therapies that can alleviate symptoms among patients with lower extremity PAD. If successful, this study will pave the way for a pivotal Phase III trial.