Lactate Clearance Goal-directed Therapy in Sepsis

Not Applicable

• Conditions: Sepsis
• Interventions: Behavioral: Lactate clearance 20% target group; Behavioral: Lactate clearance 10% target group; Behavioral: Standard EGDT group

• Registration Number: NCT03256461
• Lead Sponsor: Nanfang Hospital, Southern Medical University

Brief Summary

Serum lactate level is depended on the balance between lactate production and clearance. It is seen as a sensitive indicator reflecting not only the low systemic perfusion but microcirculatory dysfunction which cause global or regional tissue hypoxia (as a result of impaired mitochondrial oxidation). 2016 Surviving Sepsis Campaign guideline stated "We suggest guiding resuscitation to normalize lactate in patients with elevated lactate levels as a marker of tissue hypoperfusion", with weak recommendation and low quality of evidence. Several trials which evaluated the resuscitation strategy included lactate clearance as a target while based on 2.0 diagnostic criteria for sepsis, finally showed conflicting results. The aim of this study is to explore the feasibility of lactate clearance guide resuscitation in sepsis that defined by The Third International Consensus Definitions for Sepsis and Septic shock through multi-center, central-randomization clinical trial.

Detailed Description

Sepsis remains a great challenge for clinicians, early goal-directed therapy(EGDT), referring to a number of target-achieving indicators including systemic central venous oxygen saturation(ScvO2) after initial fluid resuscitation within 6 hours, has been one of the main treatment for sepsis. ScvO2 is the only indicator that reflects tissue oxygen metabolism. However, there're studies confirmed that ScvO2 oriented EGDT cannot reduce the mortality of sepsis. So it is important to find out a more effective indicator. Lactic acid is a product of anaerobic metabolism of the body, lactate clearance has been found to effectively predict the prognosis of sepsis. Few studies have shown that lactate clearance oriented fluid resuscitation can be of benefit in patients with sepsis. Nevertheless, whether lactate clearance could be combined with sepsis Bundle as a new marker to improve the prognosis remains a problem. The objective of this study is to discuss the feasibility of lactate clearance oriented sepsis treatment through multi-center clinical trial.

Study Timeline

• Status Verified: 2017-08
• Study First Submitted: 2017-08-07
• Study Start: 2017-08-21
• Study First Submitted QC: 2017-08-21
• Last Update Submitted: 2017-08-21
• Study First Posted: 2017-08-22
• Last Update Posted: 2017-08-22
• Primary Completion: 2020-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 1128

Inclusion Criteria

• Older than 17 years old.
• Primary diagnosis is sepsis, means being confirmed or suspected infection while have at least 2 points of quickSOFA(qSOFA).
• Be transferred to intensive care unit (ICU) for the first time during this hospitalization.
• Elevated lactate ≥3.0mmol/L.

Exclusion Criteria

• Acute hemorrhage uncontrolled.

• Pregnancy.

• Known liver disease - Child-Pugh classes C, acute hepatic failure, severe hepatopathy accompany with prominent portal hypertension.

• Known being in an immunosuppressive state:

  1. Suffering from any disease that is unrelated with sepsis that severely inhibits the immune to infection, such as: active hematological or lymphoma malignancy, or during immunosuppressive therapy, such as chemotherapy or radiotherapy.
  2. Known human immunodeficiency virus (HIV) serology positive.

• Known chronic kidney disease.

• Suffering from any disease that affects lactate kinetics, such as mitochondrial encephalopathy, congenital hyperlipidemia, Wernicke encephalopathy, etc. Or other probable cause of hyperlactatemia.

• Took any drugs that affect lactate kinetics within the effective time window, such as taking metformin or phenylephrine within 1 week.

• Suffering from any disease that restricts resuscitation, such as heart failure, cardiac surgery, severe heart disease etc, or suffered from a cardio-pulmonary resuscitation,.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lactate clearance 20% target group	Lactate clearance 20% target group	Lactate clearance falls by 20-percent every two hours.
Lactate clearance 10% target group	Lactate clearance 10% target group	Lactate clearance falls by 10-percent every two hours.
Standard EGDT group	Standard EGDT group	Refer to the Surviving Sepsis Campaign(SSC) 2012 sepsis guidelines within 6 h liquid resuscitation.

Primary Outcome Measures

Name	Time	Method
28-d mortality	Four years	All-cause mortality at 28 days

Secondary Outcome Measures

Name	Time	Method
ICU Length of stay	Four years	Length of stay in the intensive care unit (ICU)
Hospital Length of stay	Four years	Length of stay in hospital
90-d mortality	Four years	All-cause mortality at 90 days
Adverse events	Four years	Proportion of patients reporting treatment-emergent adverse events
In-ICU mortality	Four years	All-cause mortality during ICU stay
Administered treatments	Four years	Administered treatments included: crystalloid volume, vasopressor administered, dobutamine, red blood cell(RBC) transfusion, mechanical ventilation, renal-replacement therapy
SOFA at 24h	Four years	Sequential Organ Failure Assessment(SOFA) at 24 hours
In-hospital mortality	Four years	All-cause mortality during hospitalization

Trial Locations

Locations (1)

NanFang hospital; 🇨🇳 Guangzhou, Guangdong, China