Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial

IF 27.1 1区医学 Q1 CRITICAL CARE MEDICINE

Intensive Care Medicine Pub Date : 2025-01-07 DOI:10.1007/s00134-024-07733-9

J. Rynne, M. Mosavie, Marie-Hélène Masse, Julie Ménard, Marie-Claude Battista, David M. Maslove, Lorenzo del Sorbo, Charles St-Arnaud, Frederick DAragon, Alison Fox-Robichaud, Emmanuel Charbonney, Neill K. J. Adhikari, François Lamontagne, M. Shankar-Hari

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引用次数: 0

Abstract

Purpose

We hypothesised that the biological heterogeneity of sepsis may highlight sepsis subtypes with differences in response to intravenous vitamin C treatment in the Lessening Organ Dysfunction with VITamin C (LOVIT) trial. Our aims were to identify sepsis subtypes and to test whether sepsis subtypes have differences in treatment effect to vitamin C and describe putative biological effects of vitamin C treatment.

Methods

We measured biomarkers of inflammation, at baseline and at 7 days post-randomisation, in 457/863 (53.0%) of participants with plasma samples in the LOVIT trial. We used agglomerative hierarchical clustering on log₁₀-transformed baseline data of 26 biomarkers to identify sepsis subtypes. We analysed differences in vitamin C treatment effect with regression models incorporating robust standard errors to report odds ratio and 95% confidence intervals (OR(95% CI)). All analyses were completed blinded to treatment allocation.

Results

Our cohort included 233/429 (54.3%) allocated to vitamin C and 224/434 (51.6%) allocated to placebo. A three-subtype model best explained the variance in our data. Subtype-2 had the highest, and subtype-3 had the lowest levels of inflammatory response. In paired longitudinal samples, vitamin C did not have discernible anti-inflammatory effects, with anti-inflammatory effects related to time since randomisation and concomitant hydrocortisone treatment. The treatment effect estimates (OR (95% CI)) for subtype-1, subtype-2 and subtype-3 were 1.04 (0.63–1.73), 1.33 (0.53–3.36) and 1.95 (0.85–4.49), respectively (test of heterogeneity p = 0.002).

Conclusion

We report three sepsis subtypes based on inflammatory response profile. No subtype benefitted from vitamin C treatment in the LOVIT trial, with heterogeneity of treatment effect in the magnitude of harm.

Trial registration

Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.

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败血症亚型和维生素C的不同治疗反应：LOVIT试验的生物学亚研究

目的：在维生素C减轻器官功能障碍（LOVIT）试验中，我们假设脓毒症的生物学异质性可能突出了脓毒症亚型对静脉注射维生素C治疗的反应差异。我们的目的是确定脓毒症亚型，并测试脓毒症亚型对维生素C的治疗效果是否有差异，并描述维生素C治疗的假定生物学效应。方法：我们在基线和随机化后7天测量了457/863 (53.0%)LOVIT试验血浆样本参与者的炎症生物标志物。我们对26个生物标志物的log10转换基线数据使用聚集分层聚类来识别脓毒症亚型。我们用回归模型分析了维生素C治疗效果的差异，回归模型纳入了稳健性标准误差来报告优势比和95%置信区间（OR(95% CI)）。所有的分析都是盲法完成的。结果我们的队列包括233/429（54.3%）分配给维生素C， 224/434（51.6%）分配给安慰剂。三亚型模型最好地解释了我们数据中的差异。亚型2炎症反应最高，亚型3炎症反应最低。在成对的纵向样本中，维生素C没有明显的抗炎作用，抗炎作用与随机化和伴随氢化可的松治疗的时间有关。亚型1、亚型2和亚型3的治疗效果估计OR （95% CI）分别为1.04（0.63-1.73）、1.33（0.53-3.36）和1.95(0.85-4.49)（异质性检验p = 0.002）。结论基于炎症反应谱，我们报告了三种脓毒症亚型。在LOVIT试验中，没有任何亚型从维生素C治疗中获益，治疗效果在伤害程度上存在异质性。试验注册由乐天和约翰·赫克特纪念基金会资助；LOVIT ClinicalTrials.gov号码：NCT03680274。

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

Intensive Care Medicine 医学-危重病医学

CiteScore

51.50

自引率

2.80%

发文量

326

审稿时长

1 months

期刊介绍： Intensive Care Medicine is the premier publication platform fostering the communication and exchange of cutting-edge research and ideas within the field of intensive care medicine on a comprehensive scale. Catering to professionals involved in intensive medical care, including intensivists, medical specialists, nurses, and other healthcare professionals, ICM stands as the official journal of The European Society of Intensive Care Medicine. ICM is dedicated to advancing the understanding and practice of intensive care medicine among professionals in Europe and beyond. The journal provides a robust platform for disseminating current research findings and innovative ideas in intensive care medicine. Content published in Intensive Care Medicine encompasses a wide range, including review articles, original research papers, letters, reviews, debates, and more.