Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit

Study Overview
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Brief Summary
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The administration of intravenous fluids is ubiquitous in the care of the critically ill. Commonly available isotonic crystalloid solutions contain a broad spectrum electrolyte compositions including a range chloride concentrations. Recent studies have associated solutions with supraphysiologic chloride content with hyperchloremia, metabolic acidosis and renal vasoconstriction, acute kidney injury and renal replacement therapy, and increased mortality but no large, randomized-controlled trials have been conducted. SMART-MED will be a large, cluster-randomized, multiple-crossover trial enrolling critically ill patients from the Medical ICU at Vanderbilt University from June 2015 until April 2017. The primary endpoint will be the incidence of Major Adverse Kidney Events in 30 days after enrollment (MAKE30 is the composite of death, new renal replacement, or persistent renal dysfunction at discharge).

Detailed Description
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SMART-MED is a large, cluster-randomized, multiple-crossover trial of 0.9% saline versus physiologically-balanced isotonic crystalloids (Lactated Ringers or Plasma-Lyte© A) with regard to the incidence of major adverse kidney events by 30 days in patients admitted to the medical intensive care unit. Between June 2015 and April 2017, all patients admitted to the medical intensive care unit at Vanderbilt University medical center who are 18 years or older will be enrolled. The study will occur in one-month blocks. The ICU will be randomized to an initial fluid group (0.9% saline or physiologically balanced crystalloids). The assigned fluid will be used exclusively for all patients receiving isotonic crystalloid for the duration of the month-long block (except in the presence of pre-specified contraindications). The assigned study fluid will switch at the end of each month-long block such that half of the months are assigned to 0.9% saline and half of the months are assigned to physiologically balance fluid. It is anticipated that around 5,300 patients will be enrolled from the medical ICU during the study period. All aspects of study design, intervention, and data collection will be harmonized with an independent study addressing the same question in the non-medical intensive care units at Vanderbilt University during a similar study period (SMART-SURG). A pre-specified data analysis plan will dictate the harmonized analysis of SMART-MED and SMART-SURG.

Official Title
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Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit

Conditions
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Critical Illness, Acute Kidney Injury

Intervention / Treatment
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* Other: 0.9% Saline
* Other: Physiologically-balanced isotonic crystalloid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted to the medical intensive care unit (ICU) at Vanderbilt University Medical Center Exclusion Criteria: Age<18 years old

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 0.9% Saline<br>Patients in an ICU block randomized to physiologically-balanced isotonic fluid will receive 0.9% Saline whenever isotonic intravenous fluid administration is ordered by the treating provider. | Other: 0.9% Saline<br>* 0.9% Saline will be used whenever an isotonic crystalloid is ordered<br>* Other names: 0.9% sodium chloride;|
| Active Comparator: Physiologically-balanced<br>Patients in an ICU block randomized to physiologically-balanced isotonic fluid will receive Plasma-Lyte© A or Lactated Ringer's whenever isotonic intravenous fluid administration is ordered by the treating provider. | Other: Physiologically-balanced isotonic crystalloid<br>* Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered<br>* Other names: Plasma-Lyte© A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Adverse Kidney Event Within 30 Days | The primary outcome was the proportion of patients who met one or more criteria for a major adverse kidney event within 30 days - the composite of death, new receipt of renal-replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥200% of the baseline value) - all censored at hospital discharge or 30 days after enrollment, whichever came first. | 30 days after enrollment censored at hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day In-hospital Mortality | Death before hospital discharge, censored at 30 days after enrollment | 30 days after enrollment censored at hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crystalloid, acute kidney injury