Targeted Tissue Perfusion Versus Macrocirculatory-guided Standard Care in Patients With Septic Shock

Critical Illness Clinical Trial

— TARTARE-2S  

Official title:

Targeted Tissue Perfusion Versus Macrocirculatory-guided Standard Care in Patients With Septic Shock [TARTARE-2S]- A Multicentre Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02579525
• Other study ID #: TARTARE-2S-01
• Status: Completed
• Phase: N/A
• Start date: May 2016
• Est. completion date: December 31, 2022

Study information

• Verified date: February 2023
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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: 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: December 31, 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Septic shock defined as

1. Septic infection AND

2. systemic mean blood pressure > 65 mmHg requiring any dose of vasopressors (norepinephrine, vasopressin) despite adequate fluid resuscitation (minimum of 20 ml/kg crystalloids) AND

3. 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
• another probable cause of hyperlactatemia
• patients transferred from another ICU
• patients with active haematological malignancy

Related Conditions & MeSH terms

• Critical Illness
• Shock
• Shock, Septic
• Shock; Septic

Intervention

Other:
• Hemodynamical treatment TTP
Based on capillary refilling time, peripheral temperature, mottling, diuresis, MAP safety limit monitoring
• Hemodynamical treatment MCG
Based on MAP, CVP, urine output monitoring

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki
Switzerland	Inselspital, Bern University Hospital	Bern

Sponsors (2)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	University Hospital Inselspital, Berne

Countries where clinical trial is conducted

Finland,  Switzerland, 

References & Publications (2)

Pettila V, Merz T, Wilkman E, Perner A, Karlsson S, Lange T, Hastbacka J, Hjortrup PB, Kuitunen A, Jakob SM, Takala J. Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S): study protocol and statistical analysis plan for a randomized controlled trial. Trials. 2016 Aug 2;17:384. doi: 10.1186/s13063-016-1515-x. — View Citation

Varis E, Pettila V, Poukkanen M, Jakob SM, Karlsson S, Perner A, Takala J, Wilkman E; FINNAKI Study Group. Evolution of Blood Lactate and 90-Day Mortality in Septic Shock. A Post Hoc Analysis of the FINNAKI Study. Shock. 2017 May;47(5):574-581. doi: 10.1097/SHK.0000000000000772. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	30 days
Secondary	Time to normalization of arterial blood lactate		30 days
Secondary	Days alive with normal arterial blood lactate in 30 days		30 days
Secondary	Days alive without any inotropic or vasopressor agent in 30 days		30 days
Secondary	Days alive without renal replacement therapy (RRT) in 30 days		30 days
Secondary	Days alive without mechanical ventilation in 30 days		30 days
Secondary	Days alive without any organ support (mechanical ventilation, renal-replacement therapy, vasopressor/ inotropic agents) in 30 days		30 days
Secondary	New acute kidney injury (AKI) (Kdigo stages I-III)		30 days
Secondary	Days alive outside hospital in 90 days		90 days
Secondary	Total amount of norepinephrine given up to day 5		5 days
Secondary	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	30 days