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

NCT ID: NCT02579525

Last Updated: 2023-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2022-12-31

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:

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.

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

Conditions

Shock; Septic; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Targeted tissue perfusion guidance (TTP)

TTP-guidance based on clinical signs of peripheral perfusion.

Group Type: EXPERIMENTAL

Hemodynamical treatment TTP

Intervention Type: OTHER

Based on capillary refilling time, peripheral temperature, mottling, diuresis, MAP safety limit monitoring

Macrocirculatory - guidance (MCG)

MCG-guidance based on recommended macrocirculatory parameters.

Group Type: ACTIVE_COMPARATOR

Hemodynamical treatment MCG

Intervention Type: OTHER

Based on MAP, CVP, urine output monitoring

Interventions

Hemodynamical treatment TTP

Based on capillary refilling time, peripheral temperature, mottling, diuresis, MAP safety limit monitoring

Intervention Type: OTHER

Hemodynamical treatment MCG

Based on MAP, CVP, urine output monitoring

Intervention Type: OTHER

Eligibility Criteria

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role: collaborator

Helsinki University Central Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ville Pettilä

Professor of Intensive Care Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ville Pettilä, Prof

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Hospital/ Bern University Hospital

Stephan Jakob, Prof, Dr

Role: PRINCIPAL_INVESTIGATOR

Bern University Hospital

Locations

Helsinki University Hospital

Helsinki, , Finland

Inselspital, Bern University Hospital

Bern, , Switzerland

Countries

Finland; Switzerland

References

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.

Reference Type: BACKGROUND

PMID: 27755509 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27484695 (View on PubMed)

Other Identifiers

TARTARE-2S-01

Identifier Type: -

Identifier Source: org_study_id