Kalamar Žiga, Gorenjak Mario, Landoni Giovanni, Markota Andrej
Medical Intensive Care Unit, University Medical Centre Maribor, Maribor, Slovenia.
Centre for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Maribor, Slovenia.
PLoS One. 2025 Aug 29;20(8):e0331304. doi: 10.1371/journal.pone.0331304. eCollection 2025.
The main mechanism of hypotension in septic shock is persistent vasodilation secondary to vascular hyporeactivity despite high endogenous catecholamine levels and despite endogenous activation of the renin-angiotensin-aldosterone system. The classic stepwise approach involves initiation of norepinephrine, up-titration of the dosage to achieve a specified mean arterial pressure and moving to a second-line vasopressor if the patient remains refractory to norepinephrine. This approach often leads to prolonged states of hypoperfusion and high dose catecholamine exposure and is associated with poor clinical outcomes. Given the multifactorial basis of vasodilation in septic shock there is a strong physiological rationale for the early introduction of a multimodal vasopressor strategy that would provide a more physiologically guided approach. This study will compare the effects of a classic stepwise vs. an early balanced multimodal vasopressor strategy in septic shock.
This is a single blind randomized Phase II study. Patients with septic shock will be randomly assigned to control (classic stepwise vasopressor administration, n = 40) versus interventional (balanced multimodal vasopressor administration, n = 40) groups. The study employs a superiority trial design. Patients in the control group will be started on norepinephrine followed by vasopressin. Additional vasoactive drugs will be added as per the clinical team's decision. In the interventional group, patients will simultaneously receive norepinephrine, angiotensin II and vasopressin at equipotent starting doses. We hypothesize that balanced multimodal vasopressor administration will result in a significant decrease in renin levels compared to the conventional stepwise strategy. Several secondary and exploratory outcome measures will be investigated. Univariate statistical tests with generalized linear modeling will be used to test for significant differences between the groups.
The goal of this randomized controlled trial is to test the clinical efficacy of an early multimodal vasopressor strategy in septic shock. It aims to provide new insights and contribute to improved management of vasodilatory states.
ClinicalTrials.gov NCT06155812.
脓毒性休克中低血压的主要机制是尽管内源性儿茶酚胺水平较高且肾素 - 血管紧张素 - 醛固酮系统发生内源性激活，但仍因血管反应性降低而持续血管舒张。经典的逐步治疗方法包括开始使用去甲肾上腺素，滴定剂量以达到特定的平均动脉压，如果患者对去甲肾上腺素仍无反应则改用二线血管升压药。这种方法常常导致长时间的低灌注状态和高剂量儿茶酚胺暴露，并与不良临床结局相关。鉴于脓毒性休克中血管舒张的多因素基础，早期引入多模式血管升压药策略具有很强的生理学依据，该策略将提供更符合生理的指导方法。本研究将比较经典逐步与早期平衡多模式血管升压药策略在脓毒性休克中的效果。
这是一项单盲随机II期研究。脓毒性休克患者将被随机分配至对照组（经典逐步血管升压药给药，n = 40）和干预组（平衡多模式血管升压药给药，n = 40）。本研究采用优效性试验设计。对照组患者将开始使用去甲肾上腺素，随后使用血管加压素。根据临床团队的决定添加其他血管活性药物。在干预组中，患者将同时接受等效力起始剂量的去甲肾上腺素、血管紧张素II和血管加压素。我们假设与传统逐步策略相比，平衡多模式血管升压药给药将导致肾素水平显著降低。将研究若干次要和探索性结局指标。将使用广义线性模型的单变量统计检验来检验组间的显著差异。
这项随机对照试验的目标是测试早期多模式血管升压药策略在脓毒性休克中的临床疗效。其旨在提供新的见解并有助于改善血管舒张状态的管理。
ClinicalTrials.gov NCT06155812。
