Clinical trial NCT03251131: REVERSE-AKI Randomized Controlled Pilot Trial
Official title: REstricted Fluid Therapy VERsus Standard trEatment in Acute Kidney Injury - REVERSE-AKI Randomized Controlled Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Kidney Injury
Critical Illness
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Austin Hospital, Melbourne Australia
name: Guy's and St Thomas' NHS Foundation Trust
name: University Hospital, Ghent
name: Medical University Innsbruck
name: University of Lausanne Hospitals
First posted: 2017-08-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Observational studies among patients with acute kidney injury (AKI) have shown an association with fluid accumulation and increased mortality. Trials among other subgroups of critically ill patients have demonstrated that restricting fluid input after the initial resuscitation appears safe.

The objective if this study is to determine whether a fluid restrictive treatment regimen will lead to a lower cumulative fluid balance at 72 hours from randomization in critically ill patients with AKI and whether this approach is safe and feasible.

Detailed description: Acute kidney injury (AKI) is common in the critically ill and associates with adverse outcomes. Patients with AKI are frequently have low urine output and are at high risk of developing fluid overload. Fluid overload has been associated with an increased risk for mortality in such patients. Previous trials in critically ill patients found that a 'restrictive fluid therapy' after resuscitation was safe. Implementing a restrictive fluid therapy approach in patients with AKI may also be of benefit. To date, however, no randomized trial has been performed to evaluate the safety and feasibility of implementing a 'restrictive fluid therapy' approach compared to standard fluid therapy in patients with AKI.

In this pilot randomized controlled trial we will evaluate the implementation of a fluid restrictive approach, compared to standard therapy, in adult critically ill patients with acute kidney injury.

Eligibility criteria: Inclusion Criteria:

1. 18-years or older and admitted to critical care with an arterial line in place
2. The patient has been in critical care for at least 12 hours but no more than 72 hours
3. The patient has AKI but is not receiving acute RRT:

   For the purpose of the study AKI is defined the by the following criteria:
   1. Increase in serum creatinine over 1.5-times above baseline without a decline of 27umol/l or more from the last preceding measurement (at least 12 hours apart) AND/OR
   2. Overall urine output less than 0.5ml/kg/h (or 6ml/kg) for the previous 12h (with urine catheter in place for the period)
4. The patient is judged by the treating clinician not to be intravascularly hypovolemic
5. The patient is likely to remain in critical care for 48 hours after randomization

Exclusion Criteria:

1. Active bleeding necessitating transfusion
2. Maintenance fluid therapy is necessary due to diabetic ketoacidosis, non-ketotic coma, severe burns or other clinical reason determined by the medical staff
3. Need for RRT due to intoxication of a dialyzable toxin
4. Commencement of RRT is expected in the next 6 hours
5. On chronic renal replacement therapy (maintenance dialysis or renal transplant)
6. Presence or a strong clinical suspicion of parenchymal AKI (for example glomerulonephritis, vasculitis, acute interstitial nephritis), or post-renal obstruction
7. Severe hyponatremia (Na \<125mmol/L) or hypernatremia (Na \>155mmol/L)
8. Need for extracorporeal membrane oxygenation or molecular absorbent recirculating system (MARS-therapy)
9. Pregnant or lactating
10. Patients who are not to receive full active treatment
11. No baseline creatinine available
12. Lack of consent
13. The patient has been enrolled in another trial where co-enrollment is not feasible

Primary outcomes:
measure: Cumulative fluid balance
timeFrame: 72 hours
Secondary outcomes:
measure: Duration of acute kidney injury
timeFrame: ICU discharge/14 days
measure: Number of patients requiring renal replacement therapy
timeFrame: 14 days
measure: Cumulative fluid balance
timeFrame: 24 hours
measure: Cumulative fluid balance
timeFrame: ICU discharge/ 7 days
measure: Cumulative dose of diuretics
timeFrame: ICU discharge/ 7 days
Other outcomes:
measure: Number of patients with serious adverse events and reactions
timeFrame: 7 days
measure: Mechanical ventilation free days alive
timeFrame: 14 days
measure: Vasopressor free days and alive
timeFrame: 14 days
measure: Renal replacement therapy free days and alive
timeFrame: 90 days
measure: Dialysis dependence
timeFrame: 90 days
measure: All-cause mortality
timeFrame: 90 days
Locations:
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Canberra
country: Australia
facility: Canberra Hospital
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Lausanne
country: Switzerland
facility: Lausanne University Hospital
city: London
country: United Kingdom
facility: Guy's and St Thomas Hospital
city: London
country: United Kingdom
facility: Royal London Hospital, Barts Health NHS Trust
Study officials:
affiliation: Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
name: Suvi Vaara, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Critical Care and Nephrology, King's College London, Guy's and St Thomas Hospital, Foundation Hospital, London
name: Marlies Ostermann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vaara ST, Ostermann M, Selander T, Bitker L, Schneider A, Poli E, Hoste E, Joannidis M, Zarbock A, van Haren F, Prowle J, Pettila V, Bellomo R. Protocol and statistical analysis plan for the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-REVERSE-AKI randomized controlled pilot trial. Acta Anaesthesiol Scand. 2020 Jul;64(6):831-838. doi: 10.1111/aas.13557. Epub 2020 Feb 26.