NCT02458157

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.

Trial Health

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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Oct 2015

Geographic Reach
1 country

3 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 21, 2015

Completed
11 days until next milestone

First Posted

Study publicly available on registry

June 1, 2015

Completed
4 months until next milestone

Study Start

First participant enrolled

October 1, 2015

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 8, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 8, 2017

Completed
Last Updated

July 6, 2017

Status Verified

July 1, 2017

Enrollment Period

1.7 years

First QC Date

May 21, 2015

Last Update Submit

July 3, 2017

Conditions

Acute Kidney InjuryFluid OverloadCritical Illness

Keywords

ICUIntensiveCRRTFluid RemovalAKICritical Care

Outcome Measures

Primary Outcomes (1)

  • Cumulative fluid balance

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

    5 days

Secondary Outcomes (5)

  • Cumulative fluid balance

    ICU stay expected average of 10 days

  • Mean daily fluid balance

    ICU stay expected average of 10 days

  • Major protocol violations

    ICU stay expected average of 10 days

  • Time to neutral cumulative fluid balance

    90 days

  • Accumulated serious adverse reactions

    90 days

Other Outcomes (5)

  • All cause mortality

    90 days

  • Days alive and out of hospital

    90 days

  • Days alive and out of mechanical ventilation

    90 days

  • +2 more other outcomes

Study Arms (2)

Forced Fluid Removal

EXPERIMENTAL

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.

Drug: Furosemide (Furix)Other: Continuous renal replacement therapy (CRRT)Other: Resuscitation

Usual Care

ACTIVE COMPARATOR

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

Other: Usual Care

Interventions

Furosemide (Furix)DRUG

* 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.

Also known as: Furix
Forced Fluid Removal
Continuous renal replacement therapy (CRRT)OTHER

* 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

Also known as: CRRT
Forced Fluid Removal
ResuscitationOTHER

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: 1. Fluid removal is paused 2. A crystalloid fluid bolus of 250-500 ml is given 3. Circulatory status is reevaluated within 30 minutes 4. Step 1-3 is repeated until signs of inadequate circulation have been resolved for minimum 1 hour 5. Fluid removal is restarted in 25% reduced dose for minimum 4 hours before evaluation of effect.

Forced Fluid Removal
Usual CareOTHER

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.

Usual Care

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Aalborg Universitetshospital, Anæstesi og intensiv afdeling

Aalborg, 9000, Denmark

Location

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

Hillerød, 3400, Denmark

Location

Rigshospitale. ITA 4131 / Dept. of intensive care

København Ø, 2100, Denmark

Location

Related Publications (2)

  • 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.

    PMID: 29664109DERIVED

  • 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.

    PMID: 28438182DERIVED

MeSH Terms

Conditions

Acute Kidney InjuryEdemaCritical Illness

Interventions

FurosemideContinuous Renal Replacement TherapyResuscitation

Condition Hierarchy (Ancestors)

Renal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsDisease AttributesPathologic Processes

Intervention Hierarchy (Ancestors)

SulfanilamidesSulfonamidesAmidesOrganic ChemicalsAniline CompoundsAminesSulfonesSulfur CompoundsRenal Replacement TherapyTherapeuticsExtracorporeal CirculationSurgical Procedures, OperativeEmergency Treatment

Study Officials

  • Morten H Bestle, MD, Ph D

    Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

    PRINCIPAL INVESTIGATOR

  • Anders Perner, Md, Ph D

    Rigshospitalet. ITA 4131 / Dept of Intensive Care

    STUDY CHAIR

  • Jens-Ulrik Jensen, MD, Ph D

    Rigshospitalet, University of Copenhagen CHIP, Department of Infectious Diseases and Rheumatology, Section 2100

    STUDY CHAIR

  • Michael Ibsen, MD, Ph D

    Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

    STUDY CHAIR

  • Rasmus E Berthelsen, MD

    Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 21, 2015

First Posted

June 1, 2015

Study Start

October 1, 2015

Primary Completion

June 8, 2017

Study Completion

June 8, 2017

Last Updated

July 6, 2017

Record last verified: 2017-07

Locations

DK(3)