Temporal Changes of Lactate in CLASSIC Patients

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

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: Resuscitation fluid

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 777
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 14186
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participation in CLASSIC trial in any of the participating centres

Exclusion Criteria:

• Lack of sufficient data for analysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: European Society of Intensive Care Medicine; Region Stockholm; Collabortation for Research in Intensive Care (CRIC); The Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI)

Publications and helpful links

General Publications

• Meyhoff TS, Hjortrup PB, Wetterslev J, Sivapalan P, Laake JH, Cronhjort M, Jakob SM, Cecconi M, Nalos M, Ostermann M, Malbrain M, Pettila V, Moller MH, Kjaer MN, Lange T, Overgaard-Steensen C, Brand BA, Winther-Olesen M, White JO, Quist L, Westergaard B, Jonsson AB, Hjortso CJS, Meier N, Jensen TS, Engstrom J, Nebrich L, Andersen-Ranberg NC, Jensen JV, Joseph NA, Poulsen LM, Herlov LS, Solling CG, Pedersen SK, Knudsen KK, Straarup TS, Vang ML, Bundgaard H, Rasmussen BS, Aagaard SR, Hildebrandt T, Russell L, Bestle MH, Schonemann-Lund M, Brochner AC, Elvander CF, Hoffmann SKL, Rasmussen ML, Martin YK, Friberg FF, Seter H, Aslam TN, Adnoy S, Seidel P, Strand K, Johnstad B, Joelsson-Alm E, Christensen J, Ahlstedt C, Pfortmueller CA, Siegemund M, Greco M, Radej J, Kriz M, Gould DW, Rowan KM, Mouncey PR, Perner A; CLASSIC Trial Group. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med. 2022 Jun 30;386(26):2459-2470. doi: 10.1056/NEJMoa2202707. Epub 2022 Jun 17.

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2022
• Primary Completion (Actual): December 28, 2022
• Study Completion (Actual): June 14, 2023

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 14, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: Dnr 2021-06283-02

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