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Forced Fluid Removal in High Risk Acute Kidney Injury (FFAKI)

Primary Purpose

Acute Kidney Injury, Fluid Overload, Critical Illness

Status
Terminated
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Furosemide (Furix)
Continuous renal replacement therapy (CRRT)
Resuscitation
Usual Care
Sponsored by
Nordsjaellands Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Kidney Injury focused on measuring ICU, Intensive, CRRT, Fluid Removal, AKI, Critical Care

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age ≥ 18 years of age
  • Acute Kidney Injury defined according to the KDIGO criteria
  • Renal Recovery Score ≤ 60%. (Calculated using www.renal-recovery-score.com)
  • Fluid overload defined as a positive fluid balance ≥ 10% of ideal body weight.
  • Able to undergo randomization within 12 hours of fulfilling other inclusion criteria

Exclusion Criteria:

  • Known pre-hospitalization advanced chronic kidney disease. (eGFR < 30 mL/minute/1.73 m2 or chronic RRT.)
  • Severe hypoxic respiratory failure (use of invasive ventilation and FiO2 > 80% and PEEP > 10 cm H2O)
  • Severe burn injury (≥ 10% TBSA)
  • Severe hypo- or hyper- natremia (< 120 or > 155 mmol/l)
  • Hepatic coma
  • Mentally disabled undergoing forced treatment
  • Pregnancy/breast feeding
  • Lack of commitment for on-going life support including RRT
  • Lack of informed consent

Sites / Locations

  • Aalborg Universitetshospital, Anæstesi og intensiv afdeling
  • Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
  • Rigshospitale. ITA 4131 / Dept. of intensive care

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Forced Fluid Removal

Usual Care

Arm Description

The experimental intervention is guided by a therapeutic goal of average negative fluid balance ≥ 1 ml/kg/h and safety variables indicating inadequate circulation (lactate ≥ 4, MAP < 50 or mottling beyond the edge of kneecaps). The effect of fluid removal is evaluated three times daily (06:00. 14:00 and 22:00), while the safety variables are evaluated continuously. Resuscitation is started if one or more signs of inadequate circulation is present. The first choice for fluid removal is diuretic therapy with furosemide, which is continued for a minimum of 8 hours. If the therapeutic goal (negative fluid balance ≥ 1 ml/kg/h) is not achieved and/or maintained by furosemide alone, then fluid removal with continuous renal replacement therapy (CRRT) is initiated.

Usual Care at the discretion of the treating clinicians, except for the initiation of renal replacement therapy (RRT).

Outcomes

Primary Outcome Measures

Cumulative fluid balance
Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts.

Secondary Outcome Measures

Cumulative fluid balance
participants will be followed for the duration of ICU stay, an expected average of 10 days
Mean daily fluid balance
participants will be followed for the duration of ICU stay, an expected average of 10 days
Major protocol violations
participants will be followed for the duration of ICU stay, an expected average of 10 days
Time to neutral cumulative fluid balance
No. of days until neutral cumulative fluid balance is achieved. Participants will be followed until neutral fluid balance is achieved or they reach the end of the observation period (90 days)
Accumulated serious adverse reactions
Serious adverse reactions related to fluid removal(atrial fibrillation, ischemic events and organ failure), furosemide (severe electrolyte disturbance, severe thrombocytopenia, hearing loss agranulocytosis and allergic reactions) and the infusion of noradrenaline (cerebral hemorrhage, cardiac arrhythmia, psychiatric symptoms) will be examined

Full Information

First Posted
May 21, 2015
Last Updated
July 3, 2017
Sponsor
Nordsjaellands Hospital
Collaborators
Rigshospitalet, Denmark, Aalborg University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02458157
Brief Title
Forced Fluid Removal in High Risk Acute Kidney Injury
Acronym
FFAKI
Official Title
Forced Fluid Removal vs. Usual Intensive Care in High-risk Acute Kidney Injury With Severe Fluid Overload - A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2017
Overall Recruitment Status
Terminated
Why Stopped
Very low recruitment rates
Study Start Date
October 2015 (undefined)
Primary Completion Date
June 8, 2017 (Actual)
Study Completion Date
June 8, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nordsjaellands Hospital
Collaborators
Rigshospitalet, Denmark, Aalborg University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this pilot trial is to assess the feasibility of forced fluid removal in patients admitted to the intensive care unit (ICU) with high-risk AKI and severe fluid overload. The intervention will use furosemide infusion and/or continuous renal replacement therapy (CRRT) to achieve and maintain a neutral cumulative fluid balance. The intervention will be compared to standard of care as reflected in the kidney disease improving global outcome (KDIGO) guidelines.
Detailed Description
Acute kidney injury (AKI) is a common and serious complication in patients admitted to ICU. A core element of critical care is resuscitation with crystalloid solutions. In many cases fluid accumulates and patients become fluid overloaded (positive fluid balance > 10% of bodyweight). This is especially true in patients with AKI, since they often have impaired ability to excrete salt and water. Most observational suggests harm with increased positive fluid balance. Objectives: To assess feasibility of forced fluid removal with diuretics and/or CRRT in ICU patients with AKI and severe fluid overload, compared to current clinical practice. Design: Multicentre, parallel group, randomized, assessor blinded pilot-trial with adequate generation of allocation sequence, and allocation concealment. Trial Size: The pilot study is planned to include 50 patients. Inclusion is expected to start in August 2015.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury, Fluid Overload, Critical Illness
Keywords
ICU, Intensive, CRRT, Fluid Removal, AKI, Critical Care

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Forced Fluid Removal
Arm Type
Experimental
Arm Description
The experimental intervention is guided by a therapeutic goal of average negative fluid balance ≥ 1 ml/kg/h and safety variables indicating inadequate circulation (lactate ≥ 4, MAP < 50 or mottling beyond the edge of kneecaps). The effect of fluid removal is evaluated three times daily (06:00. 14:00 and 22:00), while the safety variables are evaluated continuously. Resuscitation is started if one or more signs of inadequate circulation is present. The first choice for fluid removal is diuretic therapy with furosemide, which is continued for a minimum of 8 hours. If the therapeutic goal (negative fluid balance ≥ 1 ml/kg/h) is not achieved and/or maintained by furosemide alone, then fluid removal with continuous renal replacement therapy (CRRT) is initiated.
Arm Title
Usual Care
Arm Type
Active Comparator
Arm Description
Usual Care at the discretion of the treating clinicians, except for the initiation of renal replacement therapy (RRT).
Intervention Type
Drug
Intervention Name(s)
Furosemide (Furix)
Other Intervention Name(s)
Furix
Intervention Description
Loading dose: 40 mg I.V. Infusion rate 40 mg/h Continued until neutral cumulative fluid balance is achieved (the overall treatment goal) or average negative fluid balance is below 1 ml/kg/h for 8 hours.
Intervention Type
Other
Intervention Name(s)
Continuous renal replacement therapy (CRRT)
Other Intervention Name(s)
CRRT
Intervention Description
Initiated in case of contraindications or inadequate effect of furosemide. Fluid removal is started at 2 ml/kg/h The efficacy is evaluated 3 times daily and removal rate increased by 0.5 ml/kg/h if the therapeutic goal is not achieved
Intervention Type
Other
Intervention Name(s)
Resuscitation
Intervention Description
The physiologic response to fluid removal is monitored with three variables indicating inadequate circulation. These are: Mottling beyond the edge of kneecaps Hypotension (MAP < 50) resistant to inotropes and vasopressors Plasma lactate ≥ 4 mmol/l Mottling and MAP are monitored continuously and lactate is measured routinely 4-6 times each day and on clinical indication. If one or more variable is present: Fluid removal is paused A crystalloid fluid bolus of 250-500 ml is given Circulatory status is reevaluated within 30 minutes Step 1-3 is repeated until signs of inadequate circulation have been resolved for minimum 1 hour Fluid removal is restarted in 25% reduced dose for minimum 4 hours before evaluation of effect.
Intervention Type
Other
Intervention Name(s)
Usual Care
Intervention Description
All interventions are performed at the discretion of the treating physician apart from initiation of renal replacement therapy which is discouraged unless one or more of the following criteria are met: Hyperkalaemia (p-K+ > 6 mmol/l) Severe metabolic acidosis attributable to AKI (pH < 7.25 and standard base excess < -10 mmol/l) resistant to IV bicarbonate infusion Severe respiratory failure with PaO2/FiO2 < 13 kPa and bilateral infiltrates/oedema on the chest x-ray. Progressive azotaemia and a blood urea nitrogen (BUN) > 25 mmol/l.
Primary Outcome Measure Information:
Title
Cumulative fluid balance
Description
Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts.
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Cumulative fluid balance
Description
participants will be followed for the duration of ICU stay, an expected average of 10 days
Time Frame
ICU stay expected average of 10 days
Title
Mean daily fluid balance
Description
participants will be followed for the duration of ICU stay, an expected average of 10 days
Time Frame
ICU stay expected average of 10 days
Title
Major protocol violations
Description
participants will be followed for the duration of ICU stay, an expected average of 10 days
Time Frame
ICU stay expected average of 10 days
Title
Time to neutral cumulative fluid balance
Description
No. of days until neutral cumulative fluid balance is achieved. Participants will be followed until neutral fluid balance is achieved or they reach the end of the observation period (90 days)
Time Frame
90 days
Title
Accumulated serious adverse reactions
Description
Serious adverse reactions related to fluid removal(atrial fibrillation, ischemic events and organ failure), furosemide (severe electrolyte disturbance, severe thrombocytopenia, hearing loss agranulocytosis and allergic reactions) and the infusion of noradrenaline (cerebral hemorrhage, cardiac arrhythmia, psychiatric symptoms) will be examined
Time Frame
90 days
Other Pre-specified Outcome Measures:
Title
All cause mortality
Time Frame
90 days
Title
Days alive and out of hospital
Time Frame
90 days
Title
Days alive and out of mechanical ventilation
Time Frame
90 days
Title
Days alive and out of renal replacement therapy
Time Frame
90 days
Title
Renal recovery
Description
Defined as 5 consecutive days of: No renal replacement therapy serum creatinine ≤ 150 % baseline value
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years of age Acute Kidney Injury defined according to the KDIGO criteria Renal Recovery Score ≤ 60%. (Calculated using www.renal-recovery-score.com) Fluid overload defined as a positive fluid balance ≥ 10% of ideal body weight. Able to undergo randomization within 12 hours of fulfilling other inclusion criteria Exclusion Criteria: Known pre-hospitalization advanced chronic kidney disease. (eGFR < 30 mL/minute/1.73 m2 or chronic RRT.) Severe hypoxic respiratory failure (use of invasive ventilation and FiO2 > 80% and PEEP > 10 cm H2O) Severe burn injury (≥ 10% TBSA) Severe hypo- or hyper- natremia (< 120 or > 155 mmol/l) Hepatic coma Mentally disabled undergoing forced treatment Pregnancy/breast feeding Lack of commitment for on-going life support including RRT Lack of informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten H Bestle, MD, Ph D
Organizational Affiliation
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anders Perner, Md, Ph D
Organizational Affiliation
Rigshospitalet. ITA 4131 / Dept of Intensive Care
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jens-Ulrik Jensen, MD, Ph D
Organizational Affiliation
Rigshospitalet, University of Copenhagen CHIP, Department of Infectious Diseases and Rheumatology, Section 2100
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Michael Ibsen, MD, Ph D
Organizational Affiliation
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Rasmus E Berthelsen, MD
Organizational Affiliation
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
Official's Role
Study Chair
Facility Information:
Facility Name
Aalborg Universitetshospital, Anæstesi og intensiv afdeling
City
Aalborg
ZIP/Postal Code
9000
Country
Denmark
Facility Name
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
City
Hillerød
ZIP/Postal Code
3400
Country
Denmark
Facility Name
Rigshospitale. ITA 4131 / Dept. of intensive care
City
København Ø
ZIP/Postal Code
2100
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
29664109
Citation
Berthelsen RE, Perner A, Jensen AK, Rasmussen BS, Jensen JU, Wiis J, Behzadi MT, Bestle MH. Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial. Acta Anaesthesiol Scand. 2018 Aug;62(7):936-944. doi: 10.1111/aas.13124. Epub 2018 Apr 17.
Results Reference
derived
PubMed Identifier
28438182
Citation
Berthelsen RE, Itenov T, Perner A, Jensen JU, Ibsen M, Jensen AEK, Bestle M. Forced fluid removal versus usual care in intensive care patients with high-risk acute kidney injury and severe fluid overload (FFAKI): study protocol for a randomised controlled pilot trial. Trials. 2017 Apr 24;18(1):189. doi: 10.1186/s13063-017-1935-2.
Results Reference
derived

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Forced Fluid Removal in High Risk Acute Kidney Injury

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