Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.
Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) trial: A phase 1 trial.
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DOI：
10.1016/j.eclinm.2021.101167
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发表时间：
2021-11
影响因子：
15.1
通讯作者：
O'Kane CM
中科院分区：
文献类型：
--
作者：
Gorman E;Shankar-Hari M;Hopkins P;Tunnicliffe WS;Perkins GD;Silversides J;McGuigan P;Krasnodembskaya A;Jackson C;Boyle R;McFerran J;McDowell C;Campbell C;McFarland M;Smythe J;Thompson J;Williams B;Curley G;Laffey JG;Clarke M;McAuley DF;O'Kane CM
间充质基质细胞(MSCs)在急性呼吸窘迫综合征(ARDS)中可能具有免疫调节、修复和抗菌作用。ORBCEL-C是一组CD362丰富的脐带源MSCs。Realist阶段1试验调查了ORBCEL-C在中到重度ARDS患者中的安全性和可行性。Realist阶段1是一项开放标签的剂量递增试验，在这项试验中，患有中到重度ARDS的机械通气患者按3+3设计接受单次静脉输注ORBCEL-C的增加剂量(100、200或400×106个细胞)。主要的安全结果是严重不良事件的发生率。剂量限制毒性定义为7天内的严重不良反应。临床试验注册.gov NCT03042143。患者入选时间为2019年1月7日至2020年1月14日。研究中，药物给药耐受性良好，三个队列中的任何一个都没有剂量限制性毒性的报道。报告了四名患者的八种不良事件。两名患者在研究用药后24小时内发热被报告为预先指定的不良事件。另有两个不良事件(非持续性室性心动过速和肝酶紊乱)被报告为不良反应。报告了四个严重的不良事件(结肠穿孔、胃穿孔、心动过缓和心肌炎)，但没有一个被认为与ORBCEL-C的使用有关。第28天，队列1(100×106)无死亡，队列2(200×106)死亡3例，队列3(400×106)死亡1例。总的第28天死亡率为44%(n=149)。单次静脉输注ORBCEL-C对中到重度ARDS患者耐受性良好。没有报告高达400×10~6个细胞的剂量限制性毒性。
Mesenchymal stromal cells (MSCs) may be of benefit in acute respiratory distress syndrome (ARDS) due to immunomodulatory, reparative, and antimicrobial actions. ORBCEL-C is a population of CD362 enriched umbilical cord-derived MSCs. The REALIST phase 1 trial investigated the safety and feasibility of ORBCEL-C in patients with moderate to severe ARDS. REALIST phase 1 was an open label, dose escalation trial in which cohorts of mechanically ventilated patients with moderate to severe ARDS received increasing doses (100, 200 or 400 × 106 cells) of a single intravenous infusion of ORBCEL-C in a 3 + 3 design. The primary safety outcome was the incidence of serious adverse events. Dose limiting toxicity was defined as a serious adverse reaction within seven days. Trial registration clinicaltrials.gov NCT03042143. Nine patients were recruited between the 7th January 2019 and 14th January 2020. Study drug administration was well tolerated and no dose limiting toxicity was reported in any of the three cohorts. Eight adverse events were reported for four patients. Pyrexia within 24 h of study drug administration was reported in two patients as pre-specified adverse events. A further two adverse events (non-sustained ventricular tachycardia and deranged liver enzymes), were reported as adverse reactions. Four serious adverse events were reported (colonic perforation, gastric perforation, bradycardia and myocarditis) but none were deemed related to administration of ORBCEL-C. At day 28 no patients had died in cohort one (100 × 106), three patients had died in cohort two (200 × 106) and one patient had died in cohort three (400 × 106). Overall day 28 mortality was 44% (n = 4/9). A single intravenous infusion of ORBCEL-C was well tolerated in patients with moderate to severe ARDS. No dose limiting toxicity was reported up to 400 × 106 cells.
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影响因子：
12.8
作者：
Chen, Jiajia;Hu, Chenxia;Li, Lanjuan
通讯作者：
Li, Lanjuan
影响因子：
4.1
作者：
Griffiths, Mark J. D.;McAuley, Danny Francis;Baudouin, Simon V.
通讯作者：
Baudouin, Simon V.
影响因子：
6.6
作者：
Cook N;Hansen AR;Siu LL;Abdul Razak AR
通讯作者：
Abdul Razak AR
DOI：
10.1001/jama.2012.25321
发表时间：
2012-12-12
期刊：
JAMA
影响因子：
--
作者：
Hare JM;Fishman JE;Gerstenblith G;DiFede Velazquez DL;Zambrano JP;Suncion VY;Tracy M;Ghersin E;Johnston PV;Brinker JA;Breton E;Davis-Sproul J;Schulman IH;Byrnes J;Mendizabal AM;Lowery MH;Rouy D;Altman P;Wong Po Foo C;Ruiz P;Amador A;Da Silva J;McNiece IK;Heldman AW;George R;Lardo A
通讯作者：
Lardo A
影响因子：
158.5
作者：
Herridge, Margaret S.;Tansey, Catherine M.;Cheung, Angela M.
通讯作者：
Cheung, Angela M.