Temporal Changes of Lactate in CLASSIC Patients

Study Overview
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Brief Summary
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This study aim to examine if randomization to different treatment strategies had any effect on the time to normalization of lactate in intensive care patients treated for septic shock.

Detailed Description
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This is a retrospective analysis of a subset of patients included in the Conservative versus Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial. In the CLASSIC trial patients with septic shock were randomized to either traditional (liberal) strategy for fluid treatment or a more conservative regimen. The study was an international multicenter clinical trial (clinicaltrials.gov NCT03668236), and results were published in New England Journal of Medicine in June 2022 (DOI: 10.1056/NEJMoa2202707). In this substudy the investigator extract all lactate values for the study period from all patients included from Karolinska University Hospital, Sundsvall and Södersjukhuset (Sweden), participating centers on Zealand (Denmark), and Plzen University Hospital (Czech Republic). Baseline data, treatment allocation and amount of fluids administered are collected as well as outcome from CLASSIC study. Primary outcome is time to lactate normalization (< 2mmol/L). Secondary outcome is lactate concentration over the first 72 hours (as peak lactate for the time intervals 0-3, 3-6, 6-12, 12-24 and then each 12h-period between 24 and 72 hours). The subgroup with blood lactate > 4mmol/L will be analyzed separately for the same end points. Time to resolution of hyperlactatemia will be modelled with a competing risks regression. Death and discharge will be competing outcomes, and administrative censoring imposed 72 hours after randomisation. Factors associated with time to lactate normalization will be examined through regression analysis. Factors that show a relationship on univariate analysis will be included in a multivariate analysis.

Official Title
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Temporal Changes in Plasma Lactate Concentration in Critically Ill Patients With Septic Shock Treated With Restrictive Compared to Standard Fluid Therapy

Conditions
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Septic Shock

Intervention / Treatment
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* Drug: Resuscitation fluid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participation in CLASSIC trial in any of the participating centres Exclusion Criteria: Lack of sufficient data for analysis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a retrospective analysis of patients recruited to an interventional multicenter trial.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conservative<br>Resuscitation fluids were only given under certain pre-defined criteria | Drug: Resuscitation fluid<br>* Cristalloid fluids given as a resuscitational intervention<br>|
| No Intervention: Traditional (liberal)<br>Patients were treated with standard of care for each site with regards to recuscitation fluids. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to resolution of hyperlactemia | Blood lactate < 2.0 mmol/L | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Temporal changes in lactate concentrations over time | Difference in blood lactate at during the first 72h from enrollment | 72 hours |