The Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care Trial

Septic Shock Clinical Trial

— CLASSIC  

Official title:

The Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03668236
• Other study ID #: RH-ITA-007
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 27, 2018
• Est. completion date: November 2022

Study information

• Verified date: April 2022
• Source: Scandinavian Critical Care Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to assess patient important benefits and harms of IV fluid restriction vs. standard care fluid therapy in patients with septic shock.

Description:

BACKGROUND:

Septic shock is common, often lethal, costly, and associated with prolonged suffering among survivors and relatives. Traditionally, intravenous (IV) fluids are used to optimise the circulation, and the use of higher volumes is recommended by international guidelines. There is, however, no high-quality evidence to support this. In contrast, data from cohort studies, small trials and systematic reviews in sepsis and large trials in other settings and patient groups suggest potential benefits from restriction of IV fluids in patients with septic shock.

OBJECTIVES:

The aim of the CLASSIC trial is to assess the benefits and harms of IV fluid restriction vs. standard care on patient-important outcome measures in adult intensive care unit (ICU) patients with septic shock.

DESIGN:

CLASSIC is an international, multicentre, parallel-grouped, open-labelled, centrally randomised, stratified, outcome assessor- and analyst-blinded trial.

POPULATION:

Adult ICU patients who have septic shock and have received at least 1 L of IV fluid in the last 24-hours.

EXPERIMENTAL INTERVENTION:

In the IV fluid restriction group no IV fluids should be given in the ICU unless extenuating circumstances occur, including signs of severe hypoperfusion, overt fluid loss or a failing GI tract with a total fluid input of less than 1 L per day. In these circumstances, IV fluid may be given in measured amounts.

CONTROL INTERVENTION:

In the standard care group there will be no upper limit for the use of IV fluids.

OUTCOMES:

The primary outcome is 90-day mortality; secondary outcomes are serious adverse events in the ICU (ischemic events or severe acute kidney injury); serious adverse reactions in the ICU; days alive without life support at day 90; days alive and out of hospital at day 90 and mortality, health-related quality of life and cognitive function at 1-year.

TRIAL SIZE:

A total of 1554 participants will be randomised to allow the detection of a 15% relative risk reduction (7% absolute) in the restrictive vs. standard care group in 90-day mortality with a power of 80%.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1554
• Est. completion date: November 2022
• Est. primary completion date: February 14, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

All the following criteria must be fulfilled:

• Aged 18 years or above

• Admitted to the ICU or plan to be admitted to the ICU regardless of trial participation

• Septic shock defined according to the Sepsis-3 criteria:

• Suspected or confirmed site of infection or positive blood culture AND

• Ongoing infusion of vasopressor/inotrope agent to maintain a mean arterial blood pressure of 65 mmHg or above AND

• Lactate of 2 mmol/L or above in any plasma sample performed within the last 3-hours

• Have received at least 1 L of IV fluid (crystalloids, colloids or blood products) in the last 24-hours prior to screening.

Exclusion Criteria:

Patients who fulfil any of the following criteria will be excluded:

• Septic shock for more than 12 hours at the time of screening as these patients are no longer early in their course

• Life-threatening bleeding as these patients need specific fluid/blood product strategies

• Acute burn injury of more than 10% of the body surface area as these patients need a specific fluid strategy

• Known pregnancy

• Consent not obtainable as per the model approved for the specific site

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

Drug:
• Isotonic crystalloids
Types of fluid to be used in both intervention groups: IV fluids given for circulatory impairment: Only isotonic crystalloids are to be used as per the Scandinavian guideline for fluid resuscitation Fluids given to substitute overt loss: Isotonic crystalloids are to be used. If large amounts of ascites are tapped, then human albumin may be used Fluids used for dehydration: Water or isotonic glucose should be used Fluids used for electrolyte disturbances: Fluids should be chosen to substitute the specific deficiency, including water in the case of severe hypernatremia Blood products are only to be used on specific indications including severe bleeding, severe anaemia and prophylactic in case of severe coagulopathy

Locations

Country	Name	City	State
Belgium	University Hospital Brussels (UZB)	Brussel
Czechia	Medical Intensive Care Unit, Fakultni Nemocnice	Plzen
Denmark	Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.	Aalborg
Denmark	Dept of Intensive Care,Copenhagen University Hospital Rigshospitalet	Copenhagen
Denmark	Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital	Copenhagen
Denmark	Dept. of Anaesthesia and Intensive Care, Herning Hospital	Herning
Denmark	Dept. of Intensive Care, Hillerød Hospital	Hillerød
Denmark	Dept. of Anaesthesia and Intensive Care, Holbæk Hospital	Holbæk
Denmark	Dept. of Anaesthesia and Intensive Care, Zealand University Hospital Køge	Køge
Denmark	Dept. of Anaesthesia and Intensive Care, Lillebaelt Hospital	Kolding
Denmark	Dept. of Anaesthesia and Intensive Care, Randers Hospital	Randers
Denmark	Dept. of Anaesthesia and Intensive Care, Zealand University Hospital Roskilde	Roskilde
Denmark	Dept. of Anaesthesia and Intensive Care, Viborg Hospital	Viborg
Italy	Dept. of Intensive Care, Ancona Hospital	Ancona
Italy	Humanitas research hospital Bergamo	Bergamo	Milan
Italy	Dept. of Intensive Care, Humanitas Research Hospital Castelanza	Castellanza	Milan
Italy	Dept. of Intensive Care, Humanitas Research Hospital	Milan
Norway	Dept. of intensive care, Østfold, Kalnes	Grålum
Norway	Dept. of intensive Care, Innlandet Hamar	Hamar
Norway	Dept. of Intensive Care, Oslo University Hospital	Oslo
Norway	Dept. of Intensive Care Medicine, Stavanger	Stavanger
Sweden	Dept. of Intensive Care Medicine, St Göran	Gothenburg
Sweden	Dept. of intensive care, Huddinge	Huddinge
Sweden	MIMA Medicinsk intermediärvårdsavdelning	Huddinge
Sweden	Dept. of Intensive Care, Solna	Solna
Sweden	Medical ICU, Karolinska, Södersjukhuset	Stockholm
Sweden	Södersjukhuset	Stockholm
Sweden	Dept. of Intensive Care Medicine Sundsvall Hospital	Sundsvall
Switzerland	Dept. of intensive care, Basel	Basel
Switzerland	Dept. of Intensive Care, University Hospital Bern	Bern
United Kingdom	Dept. of Intensive Care Unit, Guy's and St. Thomas' Hospital	London

Sponsors (4)

Lead Sponsor	Collaborator
Anders Perner	Centre for Research in Intensive Care (CRIC), Rigshospitalet, Denmark, Scandinavian Critical Care Trials Group

Countries where clinical trial is conducted

Belgium,  Czechia,  Denmark,  Italy,  Norway,  Sweden,  Switzerland,  United Kingdom, 

References & Publications (1)

Hjortrup PB, Haase N, Bundgaard H, Thomsen SL, Winding R, Pettilä V, Aaen A, Lodahl D, Berthelsen RE, Christensen H, Madsen MB, Winkel P, Wetterslev J, Perner A; CLASSIC Trial Group; Scandinavian Critical Care Trials Group. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med. 2016 Nov;42(11):1695-1705. Epub 2016 Sep 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	90-day mortality		Day 90 after randomisation
Secondary	Number of participants with one or more serious adverse events (SAEs) in the ICU defined as ischaemic events (cerebral, cardiac, intestinal or limb ischaemia) or as a new episode of severe acute kidney injury (modified KDIGO-3)		Until ICU discharge, maximum 90 days
Secondary	Number of participants with one or more serious adverse reactions (SARs) to IV crystalloids in the ICU.		Until ICU discharge, maximum 90 days
Secondary	Days alive at day 90 without life support (vasopressor / inotropic support, invasive mechanical ventilation or renal replacement therapy)		Until ICU discharge, maximum 90 days
Secondary	Days alive and out of hospital at day 90		Day 90 after randomisation
Secondary	All-cause mortality at 1-year after randomisation		1-year after randomisation
Secondary	Health-related quality of life 1-year after randomisation	Will be measured using the EuroQoL EQ-5D-5L questionnaire (comprising 5 questions with a score from 1 to 5 each and a visual analogue scale from 0 to 100). Participants who have died will be assigned the lowest possible scores.	1-year after randomisation
Secondary	Cognitive function 1-year after randomisation	Will be assessed by the Montreal Cognitive Assessment (MoCa) MINI score which is soon to be released. Participants who have died will be assigned the lowest possible score.	1-year after randomisation

External Links

•   Official study website