ArticlePloS one2025
Early multimodal vasopressor strategy in septic shock (TRICYCLE)-Study protocol for a randomized controlled clinical trial.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06155812 (Simultaneous Administration of Norepinephrine, Angiotensin II, and Vasopressin in Septic Shock Patients), which is not on this map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Simultaneous Administration of Norepinephrine, Angiotensin II, and Vasopressin in Septic Shock Patients
Who cites it
2 citing papers in PubMed.
- Clinical trials testing early multimodal vasopressor therapy require a dose ceiling, not a dose floor.Critical care (London, England) · 2026Article
- Renin and 1-year mortality in critically ill patients with ARDS: trajectories, discrimination, and survival analysis.Frontiers in medicine · 2026Article
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe 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.
methodsThis 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. DISCUSSION: 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.
trial registrationClinicalTrials.gov NCT06155812.
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