Lactate Clearance Goal-directed Therapy in Sepsis

Multi-center Clinical Trial of Lactate Clearance Goal-directed Fluid Resuscitation in Patients With Sepsis

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.

Study Overview

• Status: Unknown
• Conditions: Sepsis
• Intervention / Treatment: Behavioral: Lactate clearance 10% target group; Behavioral: Lactate clearance 20% target group; Behavioral: Standard EGDT group

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 Type: Interventional
• Enrollment (Anticipated): 1128
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Nanfang Hospital
      • Contact: Zhongqing Chen, Ph.D; Phone Number: +86 20 6164 1886; Email: 13503049103@163.com
      • Contact: Yaoyuan Zhang, Master; Email: m18620660446@163.com
      • Principal Investigator: Weijun Fu, Master
      • Sub-Investigator: Xingui Dai, Master
      • Sub-Investigator: Yaoyuan Zhang, Master

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Lactate clearance 10% target group; Lactate clearance falls by 10-percent every two hours.	Behavioral: Lactate clearance 10% target group; Participants receive the protocolized resuscitation to achieve the goal of 10-percent lactate clearance every two hours within the initial six hours of treatment.; Other Names: Lac% 10% group
EXPERIMENTAL: Lactate clearance 20% target group; Lactate clearance falls by 20-percent every two hours.	Behavioral: Lactate clearance 20% target group; Participants receive the protocolized resuscitation to achieve the goal of 20-percent lactate clearance every two hours within the initial six hours of treatment.; Other Names: Lac% 20% group
PLACEBO_COMPARATOR: Standard EGDT group; Refer to the Surviving Sepsis Campaign(SSC) 2012 sepsis guidelines within 6 h liquid resuscitation.	Behavioral: Standard EGDT group; Participants receive the strategy of early goal-directed treatment of sepsis fluid resuscitation.; Other Names: EGDT group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-d mortality	All-cause mortality at 28 days	Four years

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Investigators: Study Chair: Chen Zhongqing, Ph.D, Southern Medical University

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): August 21, 2017
• Primary Completion (ANTICIPATED): December 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: August 7, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (ACTUAL): August 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 22, 2017
• Last Update Submitted That Met QC Criteria: August 21, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: sepsis; lactate clearance; protocolized resuscitation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: LCGRIS-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No