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

NCT02079402 | Completed Phase 4

• 2 other identifiers: RH-ITA-0052014-000902-37
• Study Type: interventional
• Target: 153
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this trial is to o assess feasibility of a protocol comparing conservative (trigger guided) vs. liberal (target guided) approach to fluid resuscitation in patients with septic shock after initial fluid resuscitation.

Conditions

Septic Shock; Sepsis

Keywords

sepsis; septic; shock; ICU; intensive; critical; resuscitation; fluid; IV; crystalloid; balance

Outcome Measures

Primary Outcomes (2)

• Resuscitation volume

  5 days after randomisation

• Resuscitation volume

  Followed up until ICU discharge; an expected average of one week

Secondary Outcomes (6)

• Fluid balance

  5 days after randomisation

• Fluid balance

  Followed up until ICU discharge; an expected average of one week

• Total fluid input

  5 days after randomisation

• Total fluid input

  Followed up until ICU discharge; an expected average of one week

• Number of patients with protocol violations

  Followed up until ICU discharge; an expected average of one week

Other Outcomes (7)

• All cause mortality

  90 days after randomisation

• All-cause mortality

  Total observation time (90 days from randomisation of last patient)

• Days alive without use of mechanical ventilation

  in the 90 days from randomisation

Study Arms (2)

Liberal (target-guided) fluid resuscitation

ACTIVE COMPARATOR

Noradrenaline to MAP \>= 65 mmHg. Fluid boluses may be given as long as hemodynamic variables improve (dynamic or static variable(s) of choice). A fluid bolus is to be followed by evaluation of effect 30 minutes after the intervention at the latest. 'Variable(s) of choice' refers to the variable(s) used to assess hemodynamic improvement. Only isotonic crystalloids are to be given as resuscitation fluid; the type of isotonic crystalloid is free of choice.

Drug: Isotonic crystalloids

Conservative (trigger-guided) fluid resuscitation

EXPERIMENTAL

Noradrenaline to MAP \>= 65 mmHg. A fluid bolus of 250-500 ml may be given followed by evaluation of effect 30 minutes after the intervention at the latest if one of the following occurs: * Plasma lactate concentration ≥ 4 mmol/l at point-of-care testing. * Severe hypotension (MAP \< 50mmHg). * Mottling beyond edge of kneecap. * Severe oliguria (only in the first 2 hours after randomisation). Severe oliguria defined as urine output ≤ 0.1 ml/kg/hour IBW last hour. Only isotonic crystalloids are to be given as resuscitation fluid; the type of isotonic crystalloid is free of choice.

Drug: Isotonic crystalloids

Interventions

Isotonic crystalloids DRUG

Conservative (trigger-guided) fluid resuscitation; Liberal (target-guided) fluid resuscitation

Eligibility Criteria

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

You may qualify if:

• Adult intensive care patients (age ≥ 18 years) with sepsis defined as 2 of 4 SIRS criteria fulfilled within 24 hours and suspected or confirmed site of infection or positive blood culture.
• Suspected or confirmed circulatory impairment (hypotension/hypoperfusion/hypovolemia) for no more than 12 hours including the hours preceding ICU admission.
• At least 30 ml/kg ideal body weight (IBW) fluid (colloids, crystalloids or blood products) given in the last 6 hours.
• Shock defined as ongoing infusion of norepinephrine (any dose) to maintain blood pressure.

You may not qualify if:

• Use of any form of renal replacement therapy (RRT).
• RRT deemed imminent by the ICU doctor, i.e. RRT will be initiated within 6 hours.
• Severe hyperkalemia (p-K \> 6 mM).
• Plasma creatinine \> 350 µmol/l.
• Invasively ventilated with FiO2 \> 0.80 and PEEP \> 10 cmH2O
• Life-threatening bleeding.
• Kidney or liver transplant during current admission.
• Burns \> 10% body surface area (BSA).
• Previously enrolled in the CLASSIC trial and has finished the 90 day observation period.
• Patients for whom it has been decided not to give full life support including mechanical ventilation and RRT.
• Consent not obtainable.

Sponsors & Collaborators

• Anders Perner: lead

Study Sites (9)

Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital, Denmark.

Aalborg, Denmark

Location

Copenhagen University Hospital, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept. of Intensive Care, Herlev Hospital, Herlev, Denmark

Herlev, Denmark

Location

Dept. of Intensive Care, Herning Hospital, Herning, Denmark

Herning, Denmark

Location

Dept. of Intensive Care, Nordsjællands Hospital - Hillerød, Denmark.

Hillerød, Denmark

Location

Dept. of Intensive Care, Holbæk Hospital, Holbæk, Denmark

Holbæk, Denmark

Location

Dept. og Intensive Care, Holstebro Hospital, Denmark

Holstebro, Denmark

Location

Dept. of Intensive Care, Randers Hospital, Denmark.

Randers, Denmark

Location

Dept. of Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland.

Helsinki, Finland

Location

Related Publications (1)

• Hjortrup PB, Haase N, Bundgaard H, Thomsen SL, Winding R, Pettila 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. doi: 10.1007/s00134-016-4500-7. Epub 2016 Sep 30.

  PMID: 27686349 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis; Shock

Condition Hierarchy (Ancestors)

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

Study Officials

• Anders Perner, MD PhD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair

Study Record Dates

• First Submitted: February 28, 2014
• First Posted: March 5, 2014
• Study Start: September 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: December 9, 2015

Record last verified: 2015-12

Locations

DK (8); FI (1)