背景:仅在美国,SARSCoV-2大流行就导致超过110万人死亡。COVID-19危重患者的治疗选择有限。先前的研究表明,感染后的治疗甲型流感病毒感染小鼠的脂核苷酸CDP-胆碱,它是从头合成磷脂酰胆碱的重要前体,改善气体交换和减少肺部炎症而不改变病毒复制。在未发表的研究中,我们发现,用CDP-胆碱治疗感染SARSCoV-2的K18-hACE2转基因小鼠可预防低氧血症的发生.我们假设胞磷胆碱(CDP-胆碱的药物形式)对住院的SARSCoV-2感染的低氧性急性呼吸衰竭(HARF)患者是安全的,并且我们将获得临床益处的初步证据,以支持更大的3期试验使用一种或多种胞磷胆碱剂量。
方法:我们将进行单站点,双盲,安慰剂对照,和随机的1/2期剂量范围和安全研究Somazina®胞磷胆碱溶液注射在任何性别的同意的成年人,性别,年龄,或因SARSCoV-2相关的HARF住院的种族。该试验命名为“SCARLET”(补充胞二磷胆碱给药减少肺损伤功效试验)。我们假设SCARLET将显示静脉注射胞磷胆碱在三种剂量(0.5、2.5或5mg/kg,每12小时一次,共5天)在住院的SARSCoV-2感染HARF患者中(每剂量20例),并提供初步证据表明静脉内。胞磷胆碱可改善该人群的肺部结局。主要疗效结果将是研究第3天的SpO2:FiO2比率。探索性结果包括序贯器官衰竭评估(SOFA)评分,死腔通风指数,和肺顺应性。胞二磷胆碱对一组COVID相关的肺和血液生物标志物的影响也将被确定。
结论:胞二磷胆碱具有许多特性,对任何候选COVID-19治疗剂都是有利的,包括安全,低成本,良好的化学特性,和潜在的病原体不可知的功效。成功证明胞磷胆碱对SARSCoV-2引起的HARF重症患者有益,可以改变重症COVID患者的管理。
背景:该试验已在www注册。
结果:2023年5月31日政府(NCT05881135)。
方法:目前正在注册。
BACKGROUND: The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.
METHODS: We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety
study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The
trial is named \"SCARLET\" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy
Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the SpO2:FiO2 ratio on
study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.
CONCLUSIONS: Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.
BACKGROUND: The
trial was registered at www.
RESULTS: gov on 5/31/2023 (NCT05881135).
METHODS: Currently enrolling.