The Effect of Restrictive Fluid Management on Cardiac Function and Glycocalyx Degradation

NCT04282252 | Completed Phase 4

• 1 other identifier: FRESH
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to compare the effects of restrictive fluid management on cardiac dysfunction and vascular integrity in septic shock patients. To achieve this, patients with septic shock according to Sepsis-3 criteria admitted to several Intensive Care Units in Sweden and Denmark will be randomized to receive restrictive respectively standard fluid therapy. Blood test from these patients will be analyzed for several biomarkers of cardiac function and glycocalyx degradation. Echocardiography will also be performed to further investigate cardiac function.

Conditions

Septic Shock

Keywords

fluid therapy

Outcome Measures

Primary Outcomes (2)

• Myocardial injury

  To investigate if IV fluid restriction decreases myocardial injury measured as plasma highly sensitive Troponin T (hsTnT) concentrations.

  Compare result within 24 hours of enrolment with day 2-3 and day 7-10 or at discharge

• Hyaluronan levels

  To study the effect of conservative fluid management versus standard care on the glycocalyx by measuring the levels of hyaluronan.

  First morning after enrolment (within 24 hours from enrollment)

Secondary Outcomes (2)

• Left ventricular systolic function, MAPSE

  Compare result within 24 hours of enrolment with day 2-3 and day 7-10 or at discharge

• Difference in Syndecan-1 levels

  First morning after enrolment (within 24 hours from enrollment)

Other Outcomes (19)

• Left ventricular systolic function, global longitudinal strain

  Compare result within 24 hours of enrolment with day 2-3 and day 7-10 or at discharge

• Effect of a conservative fluid management strategy on C-terminal pro-endothelin-1 (CT-proET-1) concentrations.

  Compare result within 24 hours of enrolment with day 2-3 and day 7-10 or at discharge

• Effect of a conservative fluid management strategy on neuregulin-1 (NRG-1) concentrations.

  Compare result within 24 hours of enrolment with day 2-3 and day 7-10 or at discharge

Study Arms (2)

IV fluid restriction group

EXPERIMENTAL

No IV fluids should be given unless one of the below occurs; in these cases, IV fluid may be given: 1. In case of severe hypoperfusion or severe circulatory impairment defined by: Lactate 4 mmol/L or above or mean arterial blood pressure below 50 mm Hg or mottling beyond the kneecap or urinary output less than 0.1 mL/kg bodyweight/h, but only in the first 2 hours after randomisation. A bolus of 250-500 mL of IV crystalloid solution may be given. 2. In case of overt fluid losses (eg, vomiting, large aspirates, diarrhoea, drain losses, bleeding or ascites tap) IV fluid may be given to correct for the loss. 3. In case the oral/enteral route for water or electrolyte solutions is contraindicated or has failed, IV fluids may be given to correct dehydration or electrolyte imbalances and/or to ensure a total fluid input of 1 L per 24 hours.

Drug: I.V. SOLUTIONS

Standard care group

ACTIVE COMPARATOR

There will be no upper limit for the use of IV or oral/enteral fluids. In particular: IV fluids should be given in the case of hypoperfusion or circulatory impairment and should be continued as long as hemodynamic variables improve including static or dynamic variable(s) as chosen by the clinicians. These criteria are based on the Surviving Sepsis Campaign guideline. IV fluids should be given as maintenance if the ICU has a protocol recommending maintenance fluid. IV fluids should be given to substitute expected or observed loss, dehydration or electrolyte imbalances.

Drug: I.V. SOLUTIONS

Interventions

I.V. SOLUTIONS DRUG

All i.v. fluids used in an Intensive Care Unit.

IV fluid restriction group; Standard care group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- Patients with septic shock according to the Sepsis-3 criteria who have received at least 1 L of IV fluid in the 24 hours before screening

You may not qualify if:

• Patients who have had septic shock for more than 12 hours at the time of screening
• Patients who have life-threatening bleeding
• Patients with acute burn injury \>10% of the body surface area
• Pregnant patients
• Patients in whom consent cannot be obtained

Sponsors & Collaborators

• Karolinska Institutet: lead

Study Sites (1)

Södersjukhuset

Stockholm, 11883, Sweden

Location

Related Publications (1)

• Christensen J, Sivapalan P, Meyhoff TS, Jarnbert-Pettersson H, Perner A, Moller MH, Lange T, Hjortrup PB, Joelsson-Alm E, Jonmarker S, Sjoberg F, Martensson J, Gladh AH, Cronhjort M. Restrictive Versus Standard Intravenous Fluid Therapy and Endothelial Glycocalyx Shedding in ICU Patients With Septic Shock-A Preplanned Sub-Study of the Randomized CLASSIC Trial. Acta Anaesthesiol Scand. 2026 Jan;70(1):e70156. doi: 10.1111/aas.70156.

  PMID: 41321198 DERIVED

MeSH Terms

Conditions

Shock, Septic

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Maria Cronhjort, MD, PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 24, 2020
• Study Start: February 2, 2020
• Primary Completion: October 22, 2021
• Study Completion: April 22, 2022
• Last Updated: April 3, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)