Forced Fluid Removal in High Risk Acute Kidney Injury

Critical Illness Clinical Trial

— FFAKI  

Official title:

Forced Fluid Removal vs. Usual Intensive Care in High-risk Acute Kidney Injury With Severe Fluid Overload - A Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02458157
• Other study ID #: FFAKI
• Secondary ID: 2015-001701-13
• Status: Terminated
• Phase: Phase 4
• First received: May 21, 2015
• Last updated: July 3, 2017
• Start date: October 2015
• Est. completion date: June 8, 2017

Study information

• Verified date: July 2017
• Source: Nordsjaellands Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: June 8, 2017
• Est. primary completion date: June 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Critical Illness
• Fluid Overload
• Wounds and Injuries

Intervention

Drug:
• 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.

Other:
• 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
• 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: 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.
• 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.

Locations

Country	Name	City	State
Denmark	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

Sponsors (3)

Lead Sponsor	Collaborator
Nordsjaellands Hospital	Aalborg Universitetshospital, Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All cause mortality		90 days
Other	Days alive and out of hospital		90 days
Other	Days alive and out of mechanical ventilation		90 days
Other	Days alive and out of renal replacement therapy		90 days
Other	Renal recovery	Defined as 5 consecutive days of: No renal replacement therapy; serum creatinine = 150 % baseline value	90 days
Primary	Cumulative fluid balance	Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts.	5 days
Secondary	Cumulative fluid balance	participants will be followed for the duration of ICU stay, an expected average of 10 days	ICU stay expected average of 10 days
Secondary	Mean daily fluid balance	participants will be followed for the duration of ICU stay, an expected average of 10 days	ICU stay expected average of 10 days
Secondary	Major protocol violations	participants will be followed for the duration of ICU stay, an expected average of 10 days	ICU stay expected average of 10 days
Secondary	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)	90 days
Secondary	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	90 days