#Epi 132 - TRICYCLE Trial: Early Triple Vasopressor Therapy in Septic Shock with Prof Giovanni Landoni & Dr Žiga Kalamar

Norepinephrine first, titrate up, add vasopressin when the dose gets high, reach for a third agent when things get desperate. That stepwise approach is how most of us treat septic shock. What if all three went in together, early?

In this episode of the eCritCare Podcast, Dr Swapnil Pawar is joined by Professor Giovanni Landoni (San Raffaele Hospital, Milan) and Dr Žiga Kalamar (Medical ICU, University Medical Centre Maribor, Slovenia) to discuss the TRICYCLE trial, published in Critical Care in 2026. TRICYCLE randomised 79 patients with septic shock to early simultaneous norepinephrine, vasopressin and angiotensin II at balanced starting doses, or to conventional stepwise vasopressor escalation.

In this conversation:

• Why septic shock involves several broken vasoconstrictor pathways at once, and why one drug titrated to high doses may not be the answer
• Why a phase II mechanistic trial chose renin, not blood pressure or mortality, as its primary outcome
• The results: faster falls in renin and lactate, a 3-point SOFA improvement at 72 hours, and numerically lower mortality
• The striking drop in tachyarrhythmias, and the beta-adrenergic explanation behind it
• What went hard: strict inclusion criteria and running three infusion pumps to protocol
• A post hoc hint that high-renin patients may benefit most, and why phenotyping is still a long way off
• Angiotensin II cost and access, and what that means for resource-limited settings
• Next steps: a bigger trial powered on AKI or arrhythmias, and the idea of a meta-trial run across many small sites

Read this episode on Substack: https://critcareedu.substack.com/p/tricycle-trial-multimodal-vasopressors-septic-shock

Paper: Kalamar Ž, Landoni G, Gorenjak M, et al. Early multimodal vasopressor strategy in septic shock: results of the TRICYCLE randomized controlled trial. Crit Care. 2026. doi:10.1186/s13054-026-06323-z