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Forced Fluid Removal in High Risk Acute Kidney Injury

Phase 4
Terminated
Conditions
Acute Kidney Injury
Fluid Overload
Critical Illness
Interventions
Other: Usual Care
Other: Continuous renal replacement therapy (CRRT)
Other: Resuscitation
Registration Number
NCT02458157
Lead Sponsor
Nordsjaellands Hospital
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
21
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Forced Fluid RemovalContinuous renal replacement therapy (CRRT)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.
Forced Fluid RemovalResuscitationThe 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.
Forced Fluid RemovalFurosemide (Furix)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 CareUsual CareUsual Care at the discretion of the treating clinicians, except for the initiation of renal replacement therapy (RRT).
Primary Outcome Measures
NameTimeMethod
Cumulative fluid balance5 days

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

Secondary Outcome Measures
NameTimeMethod
Major protocol violationsICU stay expected average of 10 days

participants will be followed for the duration of ICU stay, an expected average of 10 days

Time to neutral cumulative fluid balance90 days

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 reactions90 days

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

Mean daily fluid balanceICU stay expected average of 10 days

participants will be followed for the duration of ICU stay, an expected average of 10 days

Cumulative fluid balanceICU stay expected average of 10 days

participants will be followed for the duration of ICU stay, an expected average of 10 days

Trial Locations

Locations (3)

Rigshospitale. ITA 4131 / Dept. of intensive care

🇩🇰

København Ø, Denmark

Aalborg Universitetshospital, Anæstesi og intensiv afdeling

🇩🇰

Aalborg, Denmark

Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.

🇩🇰

Hillerød, Denmark

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