Fluid Balance Neutralization During CRRT (Continuous Renal Replacement Therapy) (GO-NEUTRAL)

• ClinicalTrials.gov Identifier: NCT04801784
• Recruitment Status: Recruiting
• First Posted: March 17, 2021
• Last Update Posted: September 5, 2021
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

Brief Summary:

Fluid overload is associated with increased mortality in critically ill patients with acute kidney injury. Fluid balance controlled is associated with improved outcome in observational studies, and is deemed safe in interventional trials.

The objective of the study is to keep fluid balance neutral by matching the net ultrafiltration rate to fluid inputs in patients with vasoplegia, and treated with continuous renal replacement therapy (CRRT), while insuring its security using advanced hemodynamic monitoring with continuous cardiac output monitoring.

Condition or disease	Intervention/treatment	Phase
Fluid Overload	Procedure: Increased net ultrafiltration with advanced hemodynamic monitoring; Procedure: Zero or near-zero net ultrafiltration	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Group allocation masking to staff performing result analyses
• Primary Purpose: Other
• Official Title: Hemodynamic-guided Fluid Balance Neutralization During Continuous Renal Replacement Therapy in Critically Ill Patients: the GO NEUTRAL Randomized Controlled Multi-center Study
• Actual Study Start Date: June 30, 2021
• Estimated Primary Completion Date: June 2023
• Estimated Study Completion Date: September 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Fluid balance neutralization; Fluid balance neutralization using increased net ultrafiltration, aiming to neutralize the cumulative fluid input received over the first 72 hours of study participation.	Procedure: Increased net ultrafiltration with advanced hemodynamic monitoring; A net ultrafiltration rate of 100 ml/h or more will be applied during the first 72 hours of study participation. To insure the hemodynamic security of the intervention, it is associated with an advanced hemodynamic monitoring protocol which encompasses cardiac index, preload dependence assessment (using postural maneuvers), lactate levels and central venous pressure evaluation. The hemodynamic monitoring protocol allows the decrease or suspension of the neutral ultrafiltration rate in case of hemodynamic instability or of hemodynamic status considered at risk of worsening if net ultrafiltration rate is maintained.
Active Comparator: Standard care; Active control group of positive fluid balance during the first 72 hours of study participation with zero or near-zero net ultrafiltration.	Procedure: Zero or near-zero net ultrafiltration; The active control group aims to represent the present standard of care of net ultrafiltration management in the first 72 hours of study participation in patients with critical illness. This will be performed by setting the net ultrafiltration rate to 0 up to 25 ml/h.

Outcome Measures

Primary Outcome Measures :

1. Cumulative fluid balance [ Time Frame: 72 hours from study inclusion (H72) ]
   The cumulative fluid balance (in ml) will be calculated as the total amount of input received by the patients (including IV fluids and medications, blood products, hydration and nutrition), minus the total output over the same period of time (including urine output, net ultrafiltration, and drains). The cumulative fluid balance at H72 will be compared between study groups in alive patients at H72.

Secondary Outcome Measures :

1. Number of hemodynamic episodes [ Time Frame: 72 hours from study inclusion ]
   Hemodynamic instability is defined as the appearance of mottles, a mean arterial pressure < 65 mm Hg and requiring urgent intervention, a decrease in cardiac index > 15%, or tachycardia > 120 beats per minute (bpm).
2. Number of hemodynamic episodes with preload dependence status [ Time Frame: 72 hours from study inclusion ]
   Hemodynamic episodes defined as stated above, that were associated with preload dependence, defined as a significant increase in cardiac index when performing a postural maneuver. This test will be performed every 4 hours as part of the hemodynamic protocol
3. Number of Major Adverse Kidney Events (MAKE) [ Time Frame: 90 days from study inclusion ]
   MAKE is a composite criterion applied to participants, composed of either the persistence of renal impairment at Day90 (defined as a serum creatinine > 2 x baseline value), renal replacement therapy dependence at Day90, or death at Day90. A separate analysis of each components of the MAKE 90 outcome will be performed.
4. Mean arterial pressure [ Time Frame: Every 4 hours from inclusion to 72 hours after inclusion ]
   Repeated measurement or assessment of mean arterial pressure, cardiac index, lactatemia, and vasopressor dose will make it possible to assess the hemodynamic effect of study intervention
5. Cardiac index [ Time Frame: Every 4 hours from inclusion to 72 hours after inclusion ]
   Repeated measurement or assessment of mean arterial pressure, cardiac index, lactatemia, and vasopressor dose will make it possible to assess the hemodynamic effect of study intervention
6. Lactatemia [ Time Frame: Every 4 hours from inclusion to 72 hours after inclusion ]
   Repeated measurement or assessment of mean arterial pressure, cardiac index, lactatemia, and vasopressor dose will make it possible to assess the hemodynamic effect of study intervention
7. Vasopressor dose administered [ Time Frame: Every 4 hours from inclusion to 72 hours after inclusion ]
   Repeated measurement or assessment of mean arterial pressure, cardiac index, lactatemia, and vasopressor dose will make it possible to assess the hemodynamic effect of study intervention
8. Cumulative fluid balance [ Time Frame: 24 hours and day 7 from study inclusion ]
   The cumulative fluid balance will be calculated as stated for the primary outcome at Hours24. It will be estimated using body weight variation between inclusion and day 7.
9. Cumulative net ultrafiltration [ Time Frame: 24 hours, 72 hours and day 7 from study inclusion ]
   The cumulative net ultrafiltration is reported by CRRT (continuous renal replacement therapy) generators ad collected every 4 hours from inclusion to 72 hours after inclusion.
10. Number of respiratory and circulatory failure free days [ Time Frame: Day 28 of study inclusion ]
    Organ failure free days are defined as the number of days without organ support, and censored at 28 days of inclusion. Weaning of mechanical ventilation is defined as being free of IMV for 48 hours or more. Weaning of vasopressor is defined as being free of any vasopressor administration for 48 hours or more. Participant who die are over the 28-day period are assigned a value of 0 organ failure free days.
11. Severity of organ failures using the SOFA score [ Time Frame: from inclusion to 72 hours of study inclusion ]
    Organ failure severity is quantified using the SOFA score (Sepsis-related organ failure assessment), and is collected at inclusion, and daily until Hours 72. The SOFA score assesses 6 physiological systems: respiratory, circulatory, coagulation, liver, renal and neurological.
12. PaO2/FiO2 ratio [ Time Frame: 24 hours, 48 hours, and 72 hours from study inclusion ]
    Intensity of pulmonary hydrostatic edema will be quantified using the PaO2/FiO2 ratio variation from inclusion to Hours24, Hours48 and Hours72 of study inclusion
13. Extravascular lung water index [ Time Frame: 24 hours, 48 hours, and 72 hours from study inclusion ]
    Intensity of pulmonary hydrostatic edema will be quantified using the extravascular lung water index reported by the continuous cardiac monitoring device, from inclusion to Hours24, Hours48 and Hours72 of study inclusion
14. Hospitalisation duration [ Time Frame: Day 90 of study inclusion ]
    Hospitalisation duration will be quantified as the delay between participant admission and discharge from hospital, censored at day 90 from inclusion.
15. Duration of stay in Intensive Care Unit (ICU) [ Time Frame: Day 90 of study inclusion ]
    Duration of stay in ICU will be quantified as the delay between participant admission and discharge from ICU, censored at day 90 from inclusion
16. Survival [ Time Frame: Day 28 and 90 of study inclusion ]
    Vital status (death/alive) will be reported at D28 and D90 of study inclusion.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Patient 18 yo or more, affiliated to a social security system
• Treated with vasopressors for acute circulatory failure
• With KDIGO stage 3 acute kidney injury
• Treated with continuous renal replacement therapy for less than 24 jours
• Monitored with a calibrated continuous cardiac output device

Exclusion Criteria:

• Treatment by ECMO (extracorporeal membrane oxygenation)
• Active hemorrhage necessitating transfusion
• Maintenance dialysis or renal graft recipient
• Switch to intermittent hemodialysis is scheduled in the next 72 hours
• Acute cerebral stroke complicated by coma and under mechanical ventilation
• Acute fulminant hepatitis
• Postural maneuver (passive leg raising or Trendelenburg) cannot be performed (amputation, inferior vena cava obstruction)
• Pregnancy or lactating
• Withdrawal or limitation of care
• Moribund patient
• Patient under protective measures/wardship
• Inclusion in another trial whose main outcome is cumulative fluid balance, or whose intervention targets hemodynamic physiology, fluid balance or net ultrafiltration.
• Patient previously enrolled in the same study

Contacts and Locations

Contacts

Contact: Laurent BITKER; + 33 4 26 10 94 93; laurent.bitker@chu-lyon.fr

Contact: Jean-Christophe RICHARD; + 33 4 26 10 94 93; j-christophe.richard@chu-lyon.fr

Locations

France

Hospices Civils de Lyon - Hôpital de la Croix Rousse; Recruiting

Lyon, France, 69004

Contact: Laurent BITKER + 33 4 26 10 94 93 laurent.bitker@chu-lyon.fr

Contact: Jean-Christophe RICHARD + 33 4 26 10 94 93 j-christophe.richard@chu-lyon.fr

Principal Investigator: Laurent BITKER, MD MSc

Sub-Investigator: Jean-Christophe RICHARD, MD PhD

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

• Principal Investigator: Laurent BITKER; Hospices Civils de Lyon

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT04801784
• Other Study ID Numbers: 69HCL20_1243; 2021-A00692-39 ( Other Identifier: ANSM )
• First Posted: March 17, 2021
• Last Update Posted: September 5, 2021
• Last Verified: August 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hospices Civils de Lyon:

Fluid Overload; fluid balance; continuous renal replacement therapy; net ultrafiltration; acute kidney injury; hemodynamic monitoring; preload dependence; hemodynamic instability; acute circulatory failure; shock; deresuscitation