Targeted Tissue Perfusion Versus Macrocirculatory-guided Standard Care in Patients With Septic Shock [TARTARE-2S]- A Multicentre Randomized Controlled Trial
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Shock; Septic
- Sponsor
- Helsinki University Central Hospital
- Enrollment
- 200
- Locations
- 2
- Primary Endpoint
- Days alive in 30 days- without vasopressors/ inotropes or hyperlactatemia
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
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:
- Intervention group- Targeted tissue perfusion guided (TTP) - care.
- 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.
Detailed Description
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
Investigators
Ville Pettilä
Professor of Intensive Care Medicine
Helsinki University Central Hospital
Eligibility Criteria
Inclusion Criteria
- •Septic shock defined as
- •Septic infection AND
- •systemic mean blood pressure \> 65 mmHg requiring any dose of vasopressors (norepinephrine, vasopressin) despite adequate fluid resuscitation (minimum of 20 ml/kg crystalloids) AND
- •Elevated lactate ≥ 3.0 mmol/L with suspected hypoperfusion
Exclusion Criteria
- •aged less than 18 or over 80 years
- •any other probable condition than sepsis affecting or expected to affect the central nervous system including post cardiac arrest
- •present or suspected myocardial ischemia
- •acute pulmonary embolism
- •terminal illness and not considered for full intensive care support
- •use of extra-corporeal membrane oxygenation (ECMO)
- •known liver disease - Child-Pugh -Class B or C
- •confirmed chronic kidney disease known on admission
- •known to be pregnant or lactating
- •more than 4 hours from fulfilled inclusion criteria to randomization
Outcomes
Primary Outcomes
Days alive in 30 days- without vasopressors/ inotropes or hyperlactatemia
Time Frame: 30 days
• Days alive in 30 days with normal arterial blood lactate ( first confirmed value of \< 2 mmol/L) AND without any inotropic or vasopressor agent
Secondary Outcomes
- Days alive outside hospital in 90 days(90 days)
- Time to normalization of arterial blood lactate(30 days)
- Days alive with normal arterial blood lactate in 30 days(30 days)
- Days alive without mechanical ventilation in 30 days(30 days)
- Days alive without any inotropic or vasopressor agent in 30 days(30 days)
- Days alive without any organ support (mechanical ventilation, renal-replacement therapy, vasopressor/ inotropic agents) in 30 days(30 days)
- Days alive without renal replacement therapy (RRT) in 30 days(30 days)
- Number/ total number of the following adverse reactions(30 days)
- New acute kidney injury (AKI) (Kdigo stages I-III)(30 days)
- Total amount of norepinephrine given up to day 5(5 days)