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

Not Applicable

Completed

• Conditions: Shock; Septic; Critical Illness
• Interventions: Other: Hemodynamical treatment TTP; Other: Hemodynamical treatment MCG

• Registration Number: NCT02579525
• Lead Sponsor: Helsinki University Central Hospital

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

Study Timeline

• Study First Submitted: 2015-10-15
• Study First Submitted QC: 2015-10-16
• Study First Posted: 2015-10-19
• Study Start: 2016-05
• Primary Completion: 2022-12
• Study Completion: 2022-12-31
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-28
• Last Update Posted: 2023-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Targeted tissue perfusion guidance (TTP)	Hemodynamical treatment TTP	TTP-guidance based on clinical signs of peripheral perfusion.
Macrocirculatory - guidance (MCG)	Hemodynamical treatment MCG	MCG-guidance based on recommended macrocirculatory parameters.

Primary Outcome Measures

Name	Time	Method
Days alive in 30 days- without vasopressors/ inotropes or hyperlactatemia	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 Outcome Measures

Name	Time	Method
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	ventricular tachycardia/ fibrillation , atrial fibrillation , myocardial infarction , skin necrosis , stroke , secondary bowel ischemia, limb ischemia, numbers of serious adverse events
New acute kidney injury (AKI) (Kdigo stages I-III)	30 days
Total amount of norepinephrine given up to day 5	5 days

Trial Locations

Locations (2)

Helsinki University Hospital; 🇫🇮 Helsinki, Finland

Inselspital, Bern University Hospital; 🇨🇭 Bern, Switzerland