Clinical trial NCT03256461: Lactate Clearance Goal-directed Therapy in Sepsis
Official title: Multi-center Clinical Trial of Lactate Clearance Goal-directed Fluid Resuscitation in Patients With Sepsis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Sepsis
Keywords: sepsis
lactate clearance
protocolized resuscitation
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2017-08-22
Enrollment: 1128
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This trial is a prospective, multicenter, single-blind, parallel-group, central-randomized, controlled trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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,.

Primary outcomes:
measure: 28-d mortality
timeFrame: Four years
Secondary outcomes:
measure: ICU Length of stay
timeFrame: Four years
measure: Hospital Length of stay
timeFrame: Four years
measure: 90-d mortality
timeFrame: Four years
measure: In-hospital mortality
timeFrame: Four years
measure: In-ICU mortality
timeFrame: Four years
measure: Administered treatments
timeFrame: Four years
measure: SOFA at 24h
timeFrame: Four years
measure: Adverse events
timeFrame: Four years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: NanFang hospital
state: Guangdong
Study officials:
affiliation: Southern Medical University
name: Chen Zhongqing, Ph.D
role: STUDY_CHAIR
References: