Forced Fluid Removal in High Risk Acute Kidney Injury

NCT ID: NCT02458157

Last Updated: 2017-07-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2017-06-08

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.

Conditions

Acute Kidney Injury; Fluid Overload; Critical Illness

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Forced Fluid Removal

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.

Group Type: EXPERIMENTAL

Furosemide (Furix)

Intervention Type: 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.

Continuous renal replacement therapy (CRRT)

Intervention Type: 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

Resuscitation

Intervention Type: OTHER

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.

Usual Care

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

Group Type: ACTIVE_COMPARATOR

Usual Care

Intervention Type: OTHER

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.

Interventions

Furosemide (Furix)

• 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: DRUG

Continuous renal replacement therapy (CRRT)

• 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

Resuscitation

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.

Intervention Type: OTHER

Usual Care

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.

Intervention Type: OTHER

Other Intervention Names

Furix; CRRT

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.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: collaborator

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Nordsjaellands Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morten H Bestle, MD, Ph D

Role: PRINCIPAL_INVESTIGATOR

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

Anders Perner, Md, Ph D

Role: STUDY_CHAIR

Rigshospitalet. ITA 4131 / Dept of Intensive Care

Jens-Ulrik Jensen, MD, Ph D

Role: STUDY_CHAIR

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

Michael Ibsen, MD, Ph D

Role: STUDY_CHAIR

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

Rasmus E Berthelsen, MD

Role: STUDY_CHAIR

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

Locations

Aalborg Universitetshospital, Anæstesi og intensiv afdeling

Aalborg, , Denmark

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

Hillerød, , Denmark

Rigshospitale. ITA 4131 / Dept. of intensive care

København Ø, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 29664109 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28438182 (View on PubMed)

Other Identifiers

2015-001701-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FFAKI

Identifier Type: -

Identifier Source: org_study_id