Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.
Repair of acute respiratory distress syndrome by stromal cell administration (REALIST): a structured study protocol for an open-label dose-escalation phase 1 trial followed by a randomised, triple-blind, allocation concealed, placebo-controlled phase 2 trial.
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作者：
由于免疫调节和修复特性，间充质基质细胞 (MSC) 可能对 ARDS 有益。该试验研究了一种新型富含 CD362 的脐带衍生 MSC 产品（REALIST ORBCEL-C），该产品按照良好生产规范标准生产，用于治疗因 COVID-19 导致的中度至重度 ARDS 和其他原因引起的 ARDS 患者。第一阶段是多中心开放标签剂量递增试点试验。患者将以 3 + 3 设计接受单次 REALIST ORBCEL-C（100 × 106 细胞、200 × 106 细胞或 400 × 106 细胞）输注。第二阶段是一项多中心随机、三盲、分配隐藏安慰剂对照试验。将招募两组因 COVID-19 导致 ARDS 或因其他原因导致 ARDS 的患者，并按 1:1 随机分配接受单次输注 REALIST ORBCEL-C（400 × 106 个细胞或第一阶段的最大耐受剂量）或安慰剂。每个队列计划招募 60 名患者。主要安全性结果是严重不良事件的发生率。主要疗效结果是第 7 天的氧合指数。试验将根据报告试验综合标准 (CONSORT 2010) 声明进行报告。讨论了 NHS 基础设施内符合良好生产规范标准的先进治疗药品的开发和制造，包括试验建立早期阶段遇到的挑战。概述了在试验第 2 阶段纳入一组单独的因 COVID-19 导致的 ARDS 患者的理由。 ClinicalTrials.gov NCT03042143。注册于 2017 年 2 月 3 日。EudraCT 编号 2017-000584-33 在线版本包含可在 10.1186/s13063-022-06220-0 获取的补充材料。
Mesenchymal stromal cells (MSCs) may be of benefit in ARDS due to immunomodulatory and reparative properties. This trial investigates a novel CD362 enriched umbilical cord derived MSC product (REALIST ORBCEL-C), produced to Good Manufacturing Practice standards, in patients with moderate to severe ARDS due to COVID-19 and ARDS due to other causes. Phase 1 is a multicentre open-label dose-escalation pilot trial. Patients will receive a single infusion of REALIST ORBCEL-C (100 × 106 cells, 200 × 106 cells or 400 × 106 cells) in a 3 + 3 design. Phase 2 is a multicentre randomised, triple blind, allocation concealed placebo-controlled trial. Two cohorts of patients, with ARDS due to COVID-19 or ARDS due to other causes, will be recruited and randomised 1:1 to receive either a single infusion of REALIST ORBCEL-C (400 × 106 cells or maximal tolerated dose in phase 1) or placebo. Planned recruitment to each cohort is 60 patients. The primary safety outcome is the incidence of serious adverse events. The primary efficacy outcome is oxygenation index at day 7. The trial will be reported according to the Consolidated Standards for Reporting Trials (CONSORT 2010) statement. The development and manufacture of an advanced therapy medicinal product to Good Manufacturing Practice standards within NHS infrastructure are discussed, including challenges encountered during the early stages of trial set up. The rationale to include a separate cohort of patients with ARDS due to COVID-19 in phase 2 of the trial is outlined. ClinicalTrials.gov NCT03042143. Registered on 3 February 2017. EudraCT Number 2017-000584-33 The online version contains supplementary material available at 10.1186/s13063-022-06220-0.
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DOI：
10.1186/s13054-017-1695-0
发表时间：
2017-05-17
期刊：
Critical care (London, England)
影响因子：
--
作者：
Agus A;Hulme C;Verghis RM;McDowell C;Jackson C;O'Kane CM;Laffey JG;McAuley DF
通讯作者：
McAuley DF
影响因子：
15.1
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
通讯作者：
O'Kane CM
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
影响因子：
6
作者：
Dilogo IH;Aditianingsih D;Sugiarto A;Burhan E;Damayanti T;Sitompul PA;Mariana N;Antarianto RD;Liem IK;Kispa T;Mujadid F;Novialdi N;Luviah E;Kurniawati T;Lubis AMT;Rahmatika D
通讯作者：
Rahmatika D