Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03668236
Recruitment Status : Recruiting
First Posted : September 12, 2018
Last Update Posted : February 11, 2020
Sponsor:
Collaborators:
Rigshospitalet, Denmark
Centre for Research in Intensive Care (CRIC)
Scandinavian Critical Care Trials Group
Information provided by (Responsible Party):
Anders Perner, Scandinavian Critical Care Trials Group

Tracking Information
First Submitted Date  ICMJE September 6, 2018
First Posted Date  ICMJE September 12, 2018
Last Update Posted Date February 11, 2020
Actual Study Start Date  ICMJE November 27, 2018
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
90-day mortality [ Time Frame: Day 90 after randomisation ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2018)
  • 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) [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Number of participants with one or more serious adverse reactions (SARs) to IV crystalloids in the ICU. [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Days alive at day 90 without life support (vasopressor / inotropic support, invasive mechanical ventilation or renal replacement therapy) [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Days alive and out of hospital at day 90 [ Time Frame: Day 90 after randomisation ]
  • All-cause mortality at 1-year after randomisation [ Time Frame: 1-year after randomisation ]
  • Health-related quality of life 1-year after randomisation [ Time Frame: 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.
  • Cognitive function 1-year after randomisation [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
  • 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) [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Number of participants with one or more serious adverse reactions (SARs) to IV crystalloids in the ICU. [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Days alive at day 90 without life support (vasopressor / inotropic support, invasive mechanical ventilation or renal replacement therapy) [ Time Frame: Until ICU discharge, maximum 90 days ]
  • Days alive and out of hospital at day 90 [ Time Frame: Day 90 after randomisation ]
  • All-cause mortality at 1-year after randomisation [ Time Frame: 1-year after randomisation ]
  • Health-related quality of life 1-year after randomisation [ Time Frame: 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.
  • Cognitive function 1-year after randomisation [ Time Frame: 1-year after randomisation ]
    Will be assessed by the Montreal Cognitive Assessment (MoCa) score
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care Trial
Official Title  ICMJE The Conservative vs. Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care Trial
Brief 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.
Detailed 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); 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%.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
Outcome assessor- and analyst-blinded trial
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE 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
Study Arms  ICMJE
  • Experimental: Fluid restriction group

    No IV fluids unless one of the extenuating circumstances occur; then, IV fluid may be given in measured amounts:

    1. In case of severe hypoperfusion or severe circulatory impairment defined by either:

      • Lactate≥4 mmol/L
      • MAP<50 mmHg (with or without vasopressor/inotrope)
      • Mottling beyond the kneecap (mottling score >2) OR
      • Urinary output<0.1 mL/kg bodyweight/h, but only in the first 2hrs after randomisation

      A bolus of 250-500 ml of IV crystalloid solution may be given followed by re-evaluation

    2. In case of overt fluid losses (e.g. vomiting, large aspirates,…) IV fluid may be given to correct for the loss, but not above the volume lost.
    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 deficiencies
      • Ensure a total fluid input of 1L per 24hrs

    IV fluids may be given as carrier for medication, but the volume should be reduced to the lowest possible

    Intervention: Drug: Isotonic crystalloids
  • Active Comparator: Standard-care

    There will be no upper limit for the use of either IV or oral/enteral fluids. In particular:

    1. 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.
    2. IV fluids should be given as maintenance if the ICU has a protocol recommending maintenance fluid
    3. IV fluids should be given to substitute expected or observed loss, dehydration or electrolyte derangements
    Intervention: Drug: Isotonic crystalloids
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 10, 2018)
1554
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anders Perner, MD PhD +4535458333 anders.perner@regionh.dk
Contact: Tine Sylvest Meyhoff, MD +4535450606 classic@cric.nu
Listed Location Countries  ICMJE Belgium,   Czechia,   Denmark,   Finland,   France,   Italy,   Netherlands,   Norway,   Spain,   Sweden,   Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03668236
Other Study ID Numbers  ICMJE RH-ITA-007
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Anders Perner, Scandinavian Critical Care Trials Group
Study Sponsor  ICMJE Anders Perner
Collaborators  ICMJE
  • Rigshospitalet, Denmark
  • Centre for Research in Intensive Care (CRIC)
  • Scandinavian Critical Care Trials Group
Investigators  ICMJE
Principal Investigator: Tine Sylvest Meyhoff, MD Rigshospitalet, Denmark
PRS Account Scandinavian Critical Care Trials Group
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP