Multimodal Vasopressor Strategy in Septic Shock

NCT ID: NCT06155812

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-23
• Study Completion Date: 2026-11-30

Brief Summary

The goal of this prospective randomized controlled trial is to compare the effects of classic stepwise vs. early balanced multimodal vasopressor strategies in septic shock.

Detailed Description

CONTROL GROUP(Classic stepwise vasopressor administration):

Patients will be started on norepinephrine with increases of 0.05-0.1 mcg/kg/min up to 0.5 mcg/kg/min, followed by vasopressin (administered at a fixed dose of 0.03 IE/min). If MAP remains < 65 mmHg, norepinephrine will be titrated above dose of 0.5 mcg/kg/min until MAP ≥ 65 mmHg. Initiation of additional vasoactive drugs (epinephrine, Ang II, methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamine, milrinone, levosimendan) as per clinical team decision.

EXPERIMENTAL GROUP(Balanced multimodal vasopressor administration):

Early, simultaneous start of norepinephrine, angiotensin II and vasopressin at equivalent starting doses (equivalent to approximately 0.05 mcg/kg/min of norepinephrine). Increments of 0.05 mcg/kg/min of equivalent doses of all three vasopressors every 3-5 min until MAP ≥ 65 mmHg is reached (vasopressin will be administered at a maximum dose of 0.03 IE/min, Ang II will be administered at maximum dose of 100ng/kg/min). Initiation of additional vasoactive drugs (epinephrine, methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamine, milrinone, levosimendan) as per clinical team decision.

Conditions

Shock, Septic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

STEPWISE VASOPRESSOR SEPTIC SHOCK MANAGEMENT

Regimen: Norepinephrine increases of 0.05-0.1 mcg/kg/min up to 0.5 mcg/kg/min, followed by vasopressin (administered at a fixed dose of 0.03 IE/min). If MAP remains \< 65 mmHg, norepinephrine will be titrated above dose of 0.5 mcg/kg/min until MAP ≥ 65 mmHg. Maximum norepinephrine dose as per clinical team decision. Initiation of additional vasoactive drugs (epinephrine, Ang II methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamin, levosimendan, milrinone) as per clinical team decision.

Group Type: ACTIVE_COMPARATOR

Successive administration of vasopressors

Intervention Type: OTHER

Administration and titration of norepinephrine and vasopressin. Administration of additional vasoactive drugs (epinephrine, methylene blue, angiotensin II or dopamine) as per clinical team. Initiation of inotropes (dobutamin, levosimendan, milrinone) as per clinical team decision.

BALANCED MULTIMODAL VASOPRESSOR SEPTIC SHOCK MANAGEMENT

Regimen: Simultaneous administration of norepinephrine, angiotensin II and vasopressin at equivalent starting doses (equivalent to approximately 0.05 mcg/kg/min of norepinephrine). Increments of 0.05 mcg/kg/min of equivalent doses of all three vasopressors every 3-5 min until MAP ≥ 65 mmHg is reached (vasopressin will be administered at a maximum dose of 0.03 IE/min, AT II will be administered at a maximum dose of 100 ng/kg/min). Initiation of additional vasoactive drugs (epinephrine, methylene blue or dopamine) as per clinical team decision. Initiation of inotropes (dobutamin, levosimendan, milrinone) as per clinical team decision.

Group Type: EXPERIMENTAL

Simultaneous administration of vasopressors

Intervention Type: OTHER

Early, simultaneous administration of norepinephrine, angiotensin II, and vasopressin.

Interventions

Simultaneous administration of vasopressors

Early, simultaneous administration of norepinephrine, angiotensin II, and vasopressin.

Intervention Type: OTHER

Successive administration of vasopressors

Administration and titration of norepinephrine and vasopressin. Administration of additional vasoactive drugs (epinephrine, methylene blue, angiotensin II or dopamine) as per clinical team. Initiation of inotropes (dobutamin, levosimendan, milrinone) as per clinical team decision.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Adult patients (≥18 years).
• Sepsis (an acute change in total Sequential Organ Failure Assessment (SOFA) score ≥2 points consequent to infection) with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L despite adequate volume resuscitation (20-30ml/kg in 3 hours).
• Vasopressor requirement of ≥0,15 μg/kg/min equivalent of norepinephrine base.
• Patients are required to have central venous access and an arterial line present, and these are expected to remain present for at least the initial 72 hours of study.
• Patients are required to have an urinary catheter present, and it is expected to remain present for at least the initial 72 hours of study.
• Patients must have cardiac index (CI) >2.3 L/min/m2 (measured by bedside echocardiography, pulse contour cardiac output (PiCCO) or Swan-Ganz catheter).

Exclusion Criteria

• Death expected <24 hours.
• Pregnancy (suspected or confirmed).
• Surgery expected for source of infection.
• Inter-hospital transfer expected during first 72 hours of hospitalization.
• Liver failure with a Model for End-Stage Liver Disease (MELD) score of ≥30.
• Patients with acute mesenteric ischemia or a history of mesenteric ischemic.
• Patients with Raynaud's phenomenon, systemic sclerosis or vasospastic disease.
• Patients with active bleeding and an anticipated need (within 48 hours of initiation of the study) for transfusion of >4 units of packed red blood cells.
• Patients with a known allergy to mannitol.
• Patients on veno-arterial (VA) ECMO.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Maribor

OTHER

Sponsor Role: lead

Responsible Party

Ziga Kalamar

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Žiga Kalamar, MD

Role: PRINCIPAL_INVESTIGATOR

University Medical Centre Maribor

Locations

University Hospital Centre Zagreb

Zagreb, , Croatia

Site Status: RECRUITING

Medical intensive care unit UMC Maribor

Maribor, , Slovenia

Site Status: RECRUITING

Countries

Croatia; Slovenia

Central Contacts

Žiga Kalamar, MD

Role: CONTACT

ziga.kalamar94@gmail.com

+386 2 321 2471

Andrej Markota, MD, PhD

Role: CONTACT

Andrej.MARKOTA@ukc-mb.si

+386 2 321 2008

Facility Contacts

Ana Vujaklija, MD

Role: primary

Franci Svenšek, MD, MMed

Role: primary

Franc.SVENSEK@ukc-mb.si

+386 2 321 2850

References

Kalamar Z, Gorenjak M, Landoni G, Markota A. Early multimodal vasopressor strategy in septic shock (TRICYCLE)-Study protocol for a randomized controlled clinical trial. PLoS One. 2025 Aug 29;20(8):e0331304. doi: 10.1371/journal.pone.0331304. eCollection 2025.

Reference Type: DERIVED

PMID: 40880376 (View on PubMed)

Other Identifiers

IRP-2023/01-03

Identifier Type: -

Identifier Source: org_study_id