The Effects of Cyproheptadine on Severe COVID-19 From the I-SPY COVID Adaptive Platform Trial

IF 2.7

CHEST critical care Pub Date : 2025-12-01 Epub Date: 2025-08-06 DOI:10.1016/j.chstcc.2025.100201

Sara C. Auld MD , Fady A. Youssef MD , Timothy E. Albertson MD , Jeremy R. Beitler MD , Paul A. Berger MD , Ellen L. Burnham MD , Nathan Cobb MD , Eliot Friedman MD , Sheetal Gandotra MD , Kevin W. Gibbs MD , Jeremiah Hayanga MD , Robert Hyzy MD , Malik M.H.S. Khan MD , Jonathan L. Koff MD , Richard A. Lee MD , Nuala J. Meyer MD , Timothy Obermiller MD , Caroline Quill MD , Philip Robinson MD , Sandhya Samavedam MD , Neil Aggarwal MD

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Abstract

Background

Severe COVID-19 has been associated with hypercoagulability and platelet activation, which is known to result in excessive accumulation of serotonin. However, few studies have evaluated whether serotonergic blockade may improve clinical outcomes among those with COVID-19.

Research Question

Does cyproheptadine, an antiserotonergic drug most commonly used to treat serotonin syndrome, improve time to clinical recovery in patients with severe COVID-19?

Study Design and Methods

The Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis in COVID (I-SPY COVID) study is a phase 2, multicenter, adaptive, open-label randomized controlled trial designed to screen potential therapeutic agents rapidly to identify those with a high probability of improving outcomes for hospitalized critically ill patients with COVID-19. For this report, participants randomized to receive cyproheptadine 8 mg enterally every 8 hours for 10 days or until hospital discharge were compared with concurrently enrolled control patients who were treated with the standard of care regimen of dexamethasone and remdesivir and did not receive an investigational agent. Bayesian survival regression models were used to model the hazard functions for the 2 events of interest: (1) recovery (treating death as a competing event) and (2) overall death as a function of randomization arm and baseline COVID-19 level.

Results

From September through December 2021, 35 participants were randomized and consented to receive cyproheptadine and 61 concurrent control patients were eligible for analysis. At that point, futility criteria were met and the data monitoring committee halted further enrollment into the cyproheptadine arm. The posterior probability that cyproheptadine would increase the rate of recovery was 0.1% and the posterior probability that cyproheptadine would improve survival was 16.3%.

Interpretation

In an open-label phase 2 trial of adults critically ill with severe COVID-19, cyproheptadine did not improve recovery or survival compared with the standard of care.

Clinical Trial Registration

ClinicalTrials.gov; No.: NCT04488081; URL: www.clinicaltrials.gov

查看原文本刊更多论文

赛庚乙胺对重症COVID-19的影响——来自I-SPY COVID适应平台试验

严重的COVID-19与高凝性和血小板活化有关，已知这会导致血清素过度积累。然而，很少有研究评估血清素阻断是否可以改善COVID-19患者的临床结果。赛庚胺是一种最常用于治疗血清素综合征的抗血清素能药物，它是否能缩短重症COVID-19患者的临床康复时间？研究设计和方法通过影像学和分子分析预测患者治疗反应的系列研究（I-SPY COVID）研究是一项2期、多中心、自适应、开放标签的随机对照试验，旨在快速筛选潜在的治疗药物，以确定那些有可能改善COVID-19住院危重患者预后的药物。在本报告中，参与者随机接受每8小时8毫克的赛庚啶肠内治疗，持续10天或直到出院，并与同时入组的对照组患者进行比较，对照组患者接受地塞米松和瑞德西韦的标准护理方案治疗，未接受研究药物治疗。使用贝叶斯生存回归模型对两个相关事件的风险函数进行建模：(1)恢复（将死亡视为竞争事件）和(2)总死亡率作为随机分组组和基线COVID-19水平的函数。从2021年9月到12月，35名参与者被随机分配并同意接受赛庚乙胺治疗，61名同期对照患者符合分析条件。在这一点上，符合无效标准，数据监测委员会停止了进一步入组赛庚啶组。赛庚啶提高恢复率的后验概率为0.1%，赛庚啶提高生存率的后验概率为16.3%。在一项针对重症COVID-19成人危重患者的开放标签2期试验中，与标准治疗相比，赛庚乙胺没有改善康复或生存率。临床试验注册网站clinicaltrials .gov；否。: NCT04488081;URL: www.clinicaltrials.gov

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CHEST critical care Critical Care and Intensive Care Medicine, Pulmonary and Respiratory Medicine

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