Clinical trial NCT06155812: Multimodal Vasopressor Strategy in Septic Shock
Official title: Simultaneous Administration of Norepinephrine, Angiotensin II, and Vasopressin in Septic Shock Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Shock, Septic
Keywords: Vasopressor agents
Angiotensin II
Vasopressin
Norepinephrine
Renin
Lactate
Lead sponsor: University Medical Centre Maribor
Sponsor class: OTHER
First posted: 2023-12-04
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Vasopressors will be administered successively in the control group. In the experimental group norepinephrine, angiotensin II, and vasopressin will be administered simultaneously.
Primary purpose: TREATMENT

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, methylene blue, dobutamine, or dopamine) 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, AT II will be administered at maximum dose of 100ng/kg/min).

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.

Primary outcomes:
measure: Rate of change in renin levels
timeFrame: 72 hours
measure: Compare lactate levels
timeFrame: 72h
Secondary outcomes:
measure: Compare Δ Sequential Organ Failure Assessment (SOFA) score
timeFrame: 72 hours
measure: Compare acute kidney injury rate
timeFrame: 72 hours
Other outcomes:
measure: Survival to ICU discharge
timeFrame: From date of ICU admission until date of ICU discharge or death during ICU stay whichever came first, assessed up to 8 weeks
measure: 28-day mortality
timeFrame: 28 days after first admission to the ICU
measure: Renal replacement therapy requirement during ICU stay.
timeFrame: From date of ICU admission until date of ICU discharge or death during ICU stay whichever came first, assessed up to 8 weeks
measure: Vasopressor cumulative dose requirement.
timeFrame: 72 hours
measure: Quality of life assessment 90 days after ICU admission (using EQ-5D standardized questionnaire).
timeFrame: 90 days after ICU admission if alive
Locations:
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Maribor
country: Slovenia
facility: Medical intensive care unit UMC Maribor
Study officials:
affiliation: University Medical Centre Maribor
name: Žiga Kalamar, MD
role: PRINCIPAL_INVESTIGATOR
References: