Background: The recommended monitoring and target levels in septic shock (SSC Guidelines 2012) including mean arterial pressure (MAP) target are not based on robust clinical data. Objective: To test, if in patients with septic shock, tissue perfusion guided (TPG) treatment strategy leads to a faster resolution of hypoperfusion than the macrocirculatory target guided standard care. Design: A prospective phase II two-parallel-group open-label randomized controlled trial Interventions: 1. Intervention group- Targeted tissue perfusion guided (TTP) - care. 2. Control group - Macrocirculatory - guided (MCG) care. Randomization: 1:1 stratified according to the site and presence or absence of known hypertension. Trial size: 200 randomised patients in 4 ICUs.
Study hypothesis: Targeting at clinical tissue perfusion (in the TTP arm) will decrease the use and untoward effects of vasopressors, and result in more days alive in 30-days without vasopressor or inotropic support and without lactatemia, in comparison with standard clinical care with preference of macrocirculatory targets (MCG arm). Intervention group - Targeted tissue perfusion (TTP) care: Primary targets /registration period 1. capillary refill time (CRT) / \<3 sec/ every hour 2. skin mottling / absent / every hour 3. arterial lactate / \<2.0 mmol/l/ per 2hr 4. peripheral temperature/ warm /every hour 5. urine output/ ≥0.5 mL/kg per hour/ every hour 6. mean arterial pressure (MAP) 50-65 mmHg (minimum as a safety limit)/ continuous * if previous hypertension 65- 70 mmHg * if oliguria 2-hour trial 75-80 mmHg (If diuresis better, continue 2hr and re-evaluate) Secondary target 7. Continuous mixed venous saturation (SvO2) \>65%, if available Control group - Macrocirculatory targets guided (MCG) standard care Primary targets 1. Mean arterial pressure (MAP) 65-75 mmHg /continuous \*\* if previous hypertension 75-80 mmHg \*\*\* if oliguria \< 0.3 ml/kg, 2-hour trial 85-90 mmHg (If diuresis better, continue 2hr and re-evaluate) 2. Central venous pressure (CVP)/hourly, Adequate fluid therapy is indicated to restore clinical hypovolemia up to the recommended CVP-level of 8-12 mmHg, if needed 3. Urine output ≥ 0.5 mL/kg/h/ hourly Secondary target 4. Continuous SvO2 \>65%, if available
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
200
Based on capillary refilling time, peripheral temperature, mottling, diuresis, MAP safety limit monitoring
Based on MAP, CVP, urine output monitoring
Helsinki University Hospital
Helsinki, Finland
Inselspital, Bern University Hospital
Bern, Switzerland
Days alive in 30 days- without vasopressors/ inotropes or hyperlactatemia
• Days alive in 30 days with normal arterial blood lactate ( first confirmed value of \< 2 mmol/L) AND without any inotropic or vasopressor agent
Time frame: 30 days
Time to normalization of arterial blood lactate
Time frame: 30 days
Days alive with normal arterial blood lactate in 30 days
Time frame: 30 days
Days alive without any inotropic or vasopressor agent in 30 days
Time frame: 30 days
Days alive without renal replacement therapy (RRT) in 30 days
Time frame: 30 days
Days alive without mechanical ventilation in 30 days
Time frame: 30 days
Days alive without any organ support (mechanical ventilation, renal-replacement therapy, vasopressor/ inotropic agents) in 30 days
Time frame: 30 days
New acute kidney injury (AKI) (Kdigo stages I-III)
Time frame: 30 days
Days alive outside hospital in 90 days
Time frame: 90 days
Total amount of norepinephrine given up to day 5
Time frame: 5 days
Number/ total number of the following adverse reactions
ventricular tachycardia/ fibrillation , atrial fibrillation , myocardial infarction , skin necrosis , stroke , secondary bowel ischemia, limb ischemia, numbers of serious adverse events
Time frame: 30 days
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