Multimodal Vasopressor Strategy in Septic Shock

Shock, Septic Clinical Trial

Official title:

Simultaneous Administration of Norepinephrine, Angiotensin II, and Vasopressin in Septic Shock Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06155812
• Other study ID #: IRP-2023/01-03
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 3, 2023
• Est. completion date: November 2026

Study information

• Verified date: December 2023
• Source: University Medical Centre Maribor
• Contact: Žiga Kalamar, MD
• Phone: +386 2 321 2471
• Email: ziga.kalamar94[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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, angiotensin II, 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: November 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (= 18 years)
• Sepsis (an acute change in total 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
• Patients must have a Cardiac Index (CI) >2.3 L/min/m2 (measured by bedside echocardiography, PiCCO catheter, or Swan-Ganz catheter)

Exclusion Criteria:

• Death expected < 24 hours
• Pregnancy (suspected or confirmed)
• Surgery is expected for the source of the infection
• Inter-hospital transfer is expected during the first 72 hours of hospitalization
• Liver failure with a Model for End-Stage Liver Disease (MELD) score of = 30 (3 months observed mortality at 52.6 %)
• Patients on VA-ECMO
• Known allergy to mannitol
• Patients with systemic sclerosis or Raynaud syndrome

Related Conditions & MeSH terms

• Shock
• Shock, Septic

Intervention

Other:
• Simultaneous administration of vasopressors
Early, simultaneous administration of norepinephrine, angiotensin II, and vasopressin.
• Successive administration of vasopressors
Administration and titration of norepinephrine and administration of additional vasoactive drugs (epinephrine, methylene blue, angiotensin II, dobutamine, or dopamine) as per clinical team.

Locations

Country	Name	City	State
Slovenia	Medical intensive care unit UMC Maribor	Maribor

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Centre Maribor

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Survival to ICU discharge		From date of ICU admission until date of ICU discharge or death during ICU stay whichever came first, assessed up to 8 weeks
Other	28-day mortality		28 days after first admission to the ICU
Primary	Rate of change in renin levels	There is an increasing amount of data that renin is the best marker of tissue hypoperfusion and predictor of ICU mortality in patients with sepsis and septic shock, even outperforming lactate. Renin increased between the first and third day in non-survivors, but dropped in survivors. The rate of change in renin concentration but not lactate concentration in ICU patients over first 72 hours is associated with in hospital mortality.	72 hours
Secondary	Compare lactate levels	In critically ill patients, plasma lactate is commonly used to guide hemodynamic resuscitation. Hyperlactatemia has been widely recognized as a marker of tissue hypoxia/hypoperfusion but it can also result from increased or accelerated aerobic glycolysis during the stress response and may represent an important energy source in critically ill patients. Resuscitation to normalize lactate levels could worsen physiological status.	72 hours
Secondary	Compare ? Sequential Organ Failure Assessment (SOFA) score	The purpose is to monitor the rate of organ dysfunction. Score ranges from 0 (best) to 24 (worst) points.	72 hours
Secondary	Compare acute kidney injury rate	The purpose is to monitor acute kidney injury based on Improving Global Outcomes (KDIGO) definition and staging system.	72 hours