REVERSE-AKI Randomized Controlled Pilot Trial (REVERSE-AKI)

• ClinicalTrials.gov Identifier: NCT03251131
• Recruitment Status: Completed
• First Posted: August 16, 2017
• Last Update Posted: December 14, 2020
• Sponsor: Helsinki University Central Hospital
• Collaborators: Austin Hospital, Melbourne Australia; Guy's and St Thomas' NHS Foundation Trust; University Hospital, Ghent; Medical University Innsbruck; Lausanne University Hospital
• Information provided by (Responsible Party): Suvi Vaara, Helsinki University Central Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Kidney Injury; Critical Illness	Other: Restrictive fluid management	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: REstricted Fluid Therapy VERsus Standard trEatment in Acute Kidney Injury - REVERSE-AKI Randomized Controlled Pilot Trial
• Actual Study Start Date: November 8, 2017
• Actual Primary Completion Date: January 31, 2020
• Actual Study Completion Date: April 30, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Restrictive fluid management; Restrictive fluid management Targeting a negative or maximum 300ml positive daily fluid balance.	Other: Restrictive fluid management; Daily fluid input is restricted to drugs and nutrition. Fluid boluses and blood products can be given if clinically indicated. Matching fluid output to fluid input whenever possible using diuretics if needed, and additionally, if clinically necessary and plausible, commencing renal replacement therapy. If renal replacement therapy is not deemed clinically desirable, acceptance of a less than targeted fluid balance.
No Intervention: Standard therapy; Randomized allocation of standard care at the clinician's discretion in accordance with current best practice.

Outcome Measures

Primary Outcome Measures :

1. Cumulative fluid balance [ Time Frame: 72 hours ]

Secondary Outcome Measures :

1. Duration of acute kidney injury [ Time Frame: ICU discharge/14 days ]
   Defined according to Kidney Disease: Improving Global Outcomes criteria
2. Number of patients requiring renal replacement therapy [ Time Frame: 14 days ]
3. Cumulative fluid balance [ Time Frame: 24 hours ]
4. Cumulative fluid balance [ Time Frame: ICU discharge/ 7 days ]
5. Cumulative dose of diuretics [ Time Frame: ICU discharge/ 7 days ]

Other Outcome Measures:

1. Number of patients with serious adverse events and reactions [ Time Frame: 7 days ]

   a Ventricular tachycardia/fibrillation b. New onset of atrial fibrillation requiring medication/defibrillation c. Ischemic events i. Acute myocardial infarction ii. Cerebral ischemia verified by CT or MRI scan.

   iii. Intestinal ischemia verified by endoscopy or open surgery.

   iv. Acute peripheral limb ischemia d. Radiologically diagnosed pulmonary edema e. Adverse events related to renal replacement therapy and diuretics use f. Frequency of hypokalaemia (serum K <3.5mmol/L) g. Frequency of hypomagnesaemia (serum Mg <0.8mmol/L) h. frequency of serum pH >7.5 i. other

2. Mechanical ventilation free days alive [ Time Frame: 14 days ]
3. Vasopressor free days and alive [ Time Frame: 14 days ]
4. Renal replacement therapy free days and alive [ Time Frame: 90 days ]
5. Dialysis dependence [ Time Frame: 90 days ]
6. All-cause mortality [ Time Frame: 90 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Australia, Victoria

Austin Hospital

Melbourne, Victoria, Australia, 3048

Australia

Canberra Hospital

Canberra, Australia

Belgium

Ghent University Hospital

Ghent, Belgium

Finland

Helsinki University Hospital

Helsinki, Finland

Switzerland

Lausanne University Hospital

Lausanne, Switzerland

United Kingdom

Guy's and St Thomas Hospital

London, United Kingdom

Royal London Hospital, Barts Health NHS Trust

London, United Kingdom

Sponsors and Collaborators

Helsinki University Central Hospital

Austin Hospital, Melbourne Australia

Guy's and St Thomas' NHS Foundation Trust

University Hospital, Ghent

Medical University Innsbruck

Lausanne University Hospital

Investigators

• Principal Investigator: Suvi Vaara, MD, PhD; Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
• Principal Investigator: Marlies Ostermann, MD, PhD; Department of Critical Care and Nephrology, King's College London, Guy's and St Thomas Hospital, Foundation Hospital, London

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Vaara ST, Ostermann M, Selander T, Bitker L, Schneider A, Poli E, Hoste E, Joannidis M, Zarbock A, van Haren F, Prowle J, Pettilä 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.

• Responsible Party: Suvi Vaara, MD, PhD, Helsinki University Central Hospital
• ClinicalTrials.gov Identifier: NCT03251131
• Other Study ID Numbers: HUS/1782/2017
• First Posted: August 16, 2017
• Last Update Posted: December 14, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Acute Kidney Injury; Critical Illness; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Disease Attributes; Pathologic Processes