Protocol and statistical analysis plan for the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-REVERSE-AKI randomized controlled pilot trial.

"randomization will be stratified according to (a) the presence of clinical signs of fluid accumulation (defined by peripheral pitting edema and/or positive fluid balance with p/f ratio less than 200 mmhg) and (b) severity of aki (stage 1 vs stage 2 or 3 as defined by the kidney disease: improving global outcomes (kdigo) criteria 16 ; detailed definition presented in the supplement data s1 ).; the detailed definitions of inclusion and exclusion criteria are presented in the supplement data s1 2 6 1 18 years or older and admitted to critical care with an arterial line in place the patient has been in critical care for at least 12 hours but no more than 72 hours the patient has aki but is not receiving acute rrt: aki is defined by the following criteria: increase in serum creatinine over 1 5 times above baseline without a decline of 27 umol/l or more from the last preceding measurement (at least 12 hours apart) and/or overall urine output less than 0 5 ml kg -1 h -1 (or 6 ml/kg) for the previous12 hours (with urine catheter in place for the period) the patient is judged by the treating clinician not to be intravascularly hypovolemic the patient is likely to remain in critical care for 48 hours after randomization 2 6 2 active bleeding necessitating transfusion maintenance fluid therapy is necessary due to diabetic ketoacidosis non-ketotic coma severe burns or other clinical reason determined by the medical staff need for rrt due to intoxication of a dialyzable toxin commencement of rrt is expected in the next 6 hours on chronic rrt (maintenance dialysis or renal transplant) presence or a strong clinical suspicion of parenchymal aki (eg glomerulonephritis vasculitis acute interstitial nephritis) or post-renal obstruction severe hyponatremia (na <125 mmol/l) or hypernatremia (na >155 mmol/l) need for extracorporeal membrane oxygenation or molecular absorbent recirculating system pregnant or lactating patients who are not to receive full active treatment no baseline creatinine available lack of consent the patient has been enrolled in another trial where co-enrollment is not feasible 2 7 table 1 presents the timeline of eligibility randomization and study interventions.; we will test the feasibility of recording it the potential challenges as a result of using creatinine-based diagnostics (possible dilution and subsequently lower incidence in the standard group) and the potentially increased use of diuretics in the interventional arm that could confound the assessment of urine output criterion 19 2 8 3 mechanical ventilation-free and days alive (truncated at 14 days) vasopressor-free days and alive (truncated at 14 days) icu-free days and alive (truncated at 14 days) rrt-free days and alive (90 days) 90-day dialysis dependence 90-day mortality 2 8 4 number of patients with one or more (serious) adverse events and reactions in both arms (detailed definitions are provided in the supplement data s1 ) ventricular tachycardia/fibrillation new onset of atrial fibrillation requiring medication/defibrillation ischemic events radiologically diagnosed pulmonary edema adverse events related to rrt and diuretics use frequency of hypokalemia (serum k <3 5 mmol/l) frequency of hypomagnesemia (serum mg <0 8 mmol/l) frequency of serum ph >7 5 other screened vs recruited patients' ratio recruitment rate (patients/center/month) protocol compliance (number of patients with protocol violations in both arms) 2 9 trained research personnel will perform the data collection using an electronic platform (absolute imaginary software ltd).; the detailed list of collected data items and schedule for collected plasma samples are provided in the supplement data s1 2 10 2 10 1 statistical analyses will be performed on the intention-to-treat (itt) population defined as all randomized subjects with consent to use data in the analysis."

"CONFLICT OF INTEREST The authors report no conflict of interest."

"Funding information"

"Trial registration clinical.trials.gov NCT03251131."