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

ABSTRACT: BACKGROUND:Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setting of established AKI. Here, we present the protocol and statistical analysis plan of the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury-the REVERSE-AKI trial that compares a restrictive fluid therapy regimen to standard therapy in critically ill patients with AKI. METHODS:REVERSE-AKI is an investigator-initiated, multinational, open-label, randomized, controlled, feasibility pilot trial conducted in seven ICUs in five countries. We aim to randomize 100 critically ill patients with AKI to a restrictive fluid treatment regimen vs standard management. In the restrictive fluid therapy regimen, the daily fluid balance target is neutral or negative. The primary outcome is the cumulative fluid balance assessed after 72 hours from randomization. Secondary outcomes include safety, feasibility, duration, and severity of AKI, and outcome at 90 days (mortality and dialysis dependence). CONCLUSIONS:This is the first multinational trial investigating the feasibility and safety of a restrictive fluid therapy regimen in critically ill patients with AKI. TRIAL REGISTRATION:clinical.trials.gov NCT03251131.

SUBMITTER: Vaara ST

PROVIDER: S-EPMC7384021 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Vaara Suvi T ST Ostermann Marlies M Selander Tuomas T Bitker Laurent L Schneider Antoine A Poli Elettra E Hoste Eric E Joannidis Michael M Zarbock Alexander A van Haren Frank F Prowle John J Pettilä Ville V Bellomo Rinaldo R

Acta anaesthesiologica Scandinavica 20200226 6

<h4>Background</h4>Fluid accumulation frequently coexists with acute kidney injury (AKI) and is associated with increased risk for AKI progression and mortality. Among septic shock patients, restricted use of resuscitation fluid has been reported to reduce the risk of worsening of AKI. Restrictive fluid therapy, however, has not been studied in the setting of established AKI. Here, we present the protocol and statistical analysis plan of the REstricted fluid therapy VERsus Standard trEatment in ...[more]

PMID: 32022904

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Project description:Acute kidney injury is a common and devastating complication of critical illness, for which renal replacement therapy is frequently needed to manage severe cases. While a recent systematic review suggested that "earlier" initiation of renal replacement therapy improves survival, completed trials are limited due to small size, single-centre status, and use of variable definitions to define "early" renal replacement therapy initiation.This is an open-label pilot randomized controlled trial. One hundred critically ill patients with severe acute kidney injury will be randomly allocated 1:1 to receive "accelerated" initiation of renal replacement therapy or "standard" initiation at 12 centers across Canada. In the accelerated arm, participants will have a venous catheter placed and renal replacement therapy will be initiated within 12 hours of fulfilling eligibility. In the standard initiation arm, participants will be monitored over 7 days to identify indications for renal replacement therapy. For participants in the standard arm with persistent acute kidney injury, defined as a serum creatinine not declining >50% from the value at the time of eligibility, the initiation of RRT will be discouraged unless one or more of the following criteria are fulfilled: serum potassium ?6.0 mmol/L; serum bicarbonate ?10 mmol/L; severe respiratory failure (PaO?/FiO?<200) or persisting acute kidney injury for ?72 hours after fulfilling eligibility. The inclusion criteria are designed to identify a population of critically ill adults with severe acute kidney injury who are likely to need renal replacement therapy during their hospitalization, but not immediately. The primary outcome is protocol adherence (>90%). Secondary outcomes include measures of feasibility (proportion of eligible patients enrolled in the trial, proportion of enrolled patients followed to 90 days for assessment of vital status and the need for renal replacement therapy) and safety (occurrence of adverse events).The optimal timing of renal replacement therapy initiation in patients with severe acute kidney injury remains uncertain, representing an important knowledge gap and a priority for high-quality research. This pilot trial is necessary to establish protocol feasibility, confirm the safety of participants and obtain estimated events rates for design of a large definitive trial.NCT01557361.

Project description:BackgroundAcute kidney injury (AKI) is a common postoperative complication with an incidence of nearly 15%. Relatively balanced fluid management, flexible use of vasoactive drugs, multimodal analgesia containing non-steroidal anti-inflammatory drugs are fundamental to ERAS protocols. However, these basic tenants may lead to an increased incidence of postoperative AKI.MethodsA search was done in the PubMed, Embase, Cochrane Library and reference lists to identify relevant studies from inception until May 2020 to be included in this study. Effects were summarized using pooled risk ratios (RRs), mean differences (MDs) and corresponding 95% confidence intervals (Cls) with random effect model. Heterogeneity assessment, sensitivity analysis, and publication bias were performed.ResultsA systematic review of nineteen cohort studies covering 17,205 patients, comparing impact of ERAS with conventional care on postoperative AKI was performed. Notably, the ERAS regimen did not increase the incidence of postoperative AKI compared with standard care (RR: 1.21; 95% CI: 0.96 to 1.52; I2 = 53%). Both goal-directed fluid therapy (RR: 1.26; 95% CI: 0.99-1.61; I2 = 55%) and restrictive fluid management (RR: 1.06; 95% CI: 0.57-1.98; I2 = 60%) had no significant effect on the incidence of postoperative AKI. There was no significant statistical difference between different AKI diagnostic criteria (P = 0.43; I2 = 0%). ERAS group had significantly shorter hospital stay (MD: -1.54; 95% CI: -1.91 to -1.17; I2 = 66%). There was no statistical difference in 30-day readmission rate (RR: 0.98; 95% CI: 0.80 to 1.20; I2 = 42%), 30-day reoperation rate (RR: 0.98; 95% CI: 0.71 to 1.34; I2 = 42%) and mortality (RR: 0.81; 95% CI: 0.59 to 1.11; I2 = 0%) between the two groups.ConclusionsThis meta-analysis suggests that ERAS protocols do not increase readmission or reoperation rates and mortality while significantly reducing LOS. Most importantly, the ERAS protocol was shown to have no promoting effect on the incidence of postoperative AKI. Even GDFT and restrictive fluid management cannot avoid the occurrence of postoperative AKI, and the ERAS protocol is still worth recommending and its safety is further confirmed.

Project description:IntroductionObservational studies have linked slower and faster net ultrafiltration (UFNET) rates during kidney replacement therapy (KRT) with mortality in critically ill patients with acute kidney injury (AKI) and fluid overload. To inform the design of a larger randomised trial of patient-centered outcomes, we conduct a feasibility study to examine restrictive and liberal approaches to UFNET during continuous KRT (CKRT).Methods and analysisThis study is an investigator-initiated, unblinded, 2-arm, comparative-effectiveness, stepped-wedged, cluster randomised trial among 112 critically ill patients with AKI treated with CKRT in 10 intensive care units (ICUs) across 2 hospital systems. In the first 6 months, all ICUs started with a liberal UFNET rate strategy. Thereafter, one ICU is randomised to the restrictive UFNET rate strategy every 2 months. In the liberal group, the UFNET rate is maintained between 2.0 and 5.0 mL/kg/hour; in the restrictive group, the UFNET rate is maintained between 0.5 and 1.5 mL/kg/hour. The three coprimary feasibility outcomes are (1) between-group separation in mean delivered UFNET rates; (2) protocol adherence; and (3) patient recruitment rate. Secondary outcomes include daily and cumulative fluid balance, KRT and mechanical ventilation duration, organ failure-free days, ICU and hospital length of stay, hospital mortality and KRT dependence at hospital discharge. Safety endpoints include haemodynamics, electrolyte imbalance, CKRT circuit issues, organ dysfunction related to fluid overload, secondary infections and thrombotic and haematological complications.Ethics and disseminationThe University of Pittsburgh Human Research Protection Office approved the study, and an independent Data and Safety Monitoring Board monitors the study. A grant from the United States National Institute of Diabetes and Digestive and Kidney Diseases sponsors the study. The trial results will be submitted for publication in peer-reviewed journals and presented at scientific conferences.Trial registration numberThis trial has been prospectively registered with clinicaltrials.gov (NCT05306964). Protocol version identifier and date: 1.5; 13 June 2023.

Project description:BackgroundThe KERALINK trial tests the hypothesis that corneal cross-linking (CXL) treatment reduces the progression of keratoconus in comparison to standard care in patients aged 10-16?years. This article describes the statistical analysis plan for this trial as an update to the published protocol. It is written before the end of the patient follow-up, while the outcome of the trial is still unknown.Design and methodsKERALINK is a randomised controlled, observer-masked, multicentre trial in progressive keratoconus comparing epithelium-off CXL with standard care, including spectacles or contact lenses as necessary for best-corrected acuity. Keratoconus is a disorder of the shape of the cornea in which the normally round dome-shaped clear front window of the eye (cornea) thins progressively leading to a cone-like bulge. This impairs the ability of the eye to focus properly, causing reduced vision which requires spectacle or contact lens wear or, in a minority of patients, eventually corneal replacement by a transplant for best vision. The primary outcome measure is the between-group difference in K2 at 18?months adjusted for K2 at baseline examination. K2 is the value of the steepest corneal meridian as measured on Pentacam topography. Secondary outcomes are keratoconus progression, time to keratoconus progression, visual acuity, refraction, apical corneal thickness and adverse events. Patient-reported effects will be explored by questionnaires. We describe in detail the statistical aspects of KERALINK: the outcome measures, the sample size calculation, general analysis principles, the planned descriptive statistics and statistical models, and planned subgroup and sensitivity analyses.DiscussionThe KERALINK statistical analysis will provide comprehensive and precise information on the relative effectiveness of the two treatments. The plan will be implemented in May 2020 when follow-up for the trial is completed.Trial registrationEudraCT, 2016-001460-11. Registered on 19 May 2016.

Project description:BackgroundDespite the evidence for calibrated cardiac monitored devices to determine fluid responsiveness, there is minimal evidence that the use of cardiac output monitor devices leads to an overall change in IV fluid use. We sought to investigate the feasibility of performing a randomised controlled study using calibrated cardiac output monitoring devices in shocked ICU patients and whether the use of these devices led to a difference in total volume of IV fluid administered.MethodsWe performed a single-centre non-blinded randomised controlled study which included patients who met the clinical criteria for shock on admission to ICU. Patients were divided into two groups (cardiac output monitors or standard) by block randomisation. Patients allocated to the cardiac output monitor all received EV1000 with Volume View sets. Daily intravenous fluid administration and cumulative fluid balance was recorded for 3?days. The primary outcome assessed was the difference in daily intravenous fluid administration and cumulative fluid balance at 72?h between the two groups. We also assessed how often the clinicians used the cardiac monitor to guide fluid therapy and the different reasoning for initiating further intravenous fluids.ResultsEighty patients were randomised and 37 received calibrated cardiac output monitors. We found no adverse outcomes in the use of calibrated cardiac output monitoring devices and that was feasible to perform a randomised controlled trial. There was no significant difference between the standard care group vs the cardiac monitoring group for cumulative fluid balance (2503?±?3764?ml vs 2458?±?3560?ml, p =?0.96). There was no significant difference between the groups for daily intravenous fluid administration on days 1, 2 or 3. In the cardiac monitored group, only 43% of the time was the EV1000 output incorporated into the decision to give further intravenous fluids.ConclusionIt is feasible to perform a randomised controlled trial using calibrated cardiac output monitoring devices. In addition, there was no trend to suggest that the use of a cardiac monitors leads to lower IV fluid use in the shocked patient. Further trials will require study designs to optimise the use of a cardiac output monitor to determine the utility of these devices in the shocked patient.Trial registrationANZCTR, ACTRN12618001373268. Registered 15 August 2018-retrospectively registered.

Project description:Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant.The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of <2 mmol/L) and without any inotropic or vasopressor agent. Secondary outcomes include individual components of the primary outcome, days alive without renal replacement, days alive without mechanical ventilation in 30 days, and new acute kidney injury. The sample size enables detection of a 13.5-h difference in the primary outcome with a type 1 error of 5 % and power of 80 %, assuming 25 % mortality and a mean of 650 h (SD 30) among the 30-day survivors. After 150 included patients the statistician masked for allocation group will recalculate the sample size potentially increasing the sample up to 300. The Data Safety and Monitoring Board (DSMB) will review the safety data after 100 patients.The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality.ClinicalTrials.gov: NCT02579525 . Registered on 19 October 2015.

Dataset Information

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

Publications

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

Similar Datasets

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