Acute Kidney Injury, Critical Illness
Conditions
Keywords
crystalloid, acute kidney injury
Brief summary
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
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.
Interventions
OTHER0.9% Saline
0.9% Saline will be used whenever an isotonic crystalloid is ordered
Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered
Sponsors
Vanderbilt University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to the medical intensive care unit (ICU) at Vanderbilt University Medical Center
Exclusion criteria
* Age\<18 years old
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Adverse Kidney Event Within 30 Days | 30 days after enrollment censored at hospital discharge | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-day In-hospital Mortality | 30 days after enrollment censored at hospital discharge | Death before hospital discharge, censored at 30 days after enrollment |
Countries
United States
Participant flow
Pre-assignment details
For randomization, we will generate two sequences of study group assignment (\[1\] saline during odd-numbered months and balanced crystalloid during even-numbered months; \[2\] balanced crystalloid during odd-numbered months and saline during even-numbered months). Participants will only receive 1 of the 2 interventions.
Participants by arm
| Arm | Count |
|---|---|
| 0.9% Sodium Chloride (Saline) Patients in an ICU block randomized to saline will receive 0.9% sodium chloride whenever isotonic intravenous fluid administration is ordered by the treating provider.
Saline: 0.9% sodium chloride will be used whenever an isotonic crystalloid is ordered | 2,646 |
| Balanced Crystalloid Patients in an ICU block randomized to balanced crystalloid will receive Plasma-Lyte A or Lactated Ringer's whenever isotonic intravenous crystalloid administration is ordered by the treating provider.
Balanced crystalloid: Lactated Ringers or Plasma-Lyte A will be used whenever an isotonic crystalloid is ordered | 2,735 |
| Total | 5,381 |
Baseline characteristics
| Characteristic | Balanced Crystalloid | Total | 0.9% Sodium Chloride (Saline) |
|---|---|---|---|
| Age, Continuous | 56 years | 56 years | 56 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 703 Participants | 1371 Participants | 668 Participants |
| Race (NIH/OMB) White | 2032 Participants | 4010 Participants | 1978 Participants |
| Sex: Female, Male Female | 1294 Participants | 2545 Participants | 1251 Participants |
| Sex: Female, Male Male | 1441 Participants | 2836 Participants | 1395 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 467 / 2,646 | 418 / 2,735 |
| other Total, other adverse events | 0 / 2,646 | 0 / 2,735 |
| serious Total, serious adverse events | 0 / 2,646 | 0 / 2,735 |
Outcome results
Primary
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.
Time frame: 30 days after enrollment censored at hospital discharge
Population: Of the 15,802 patient enrolled in the SMART trial, 5381 were admitted to the medical ICU, 2646 in the saline group and 2735 in the balanced crystalloid group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride (Saline) | Major Adverse Kidney Event Within 30 Days | 659 Participants |
| Balanced Crystalloid | Major Adverse Kidney Event Within 30 Days | 615 Participants |
p-value: <0.0595% CI: [0.77, 0.99]Regression, Logistic
Secondary
30-day In-hospital Mortality
Death before hospital discharge, censored at 30 days after enrollment
Time frame: 30 days after enrollment censored at hospital discharge
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride (Saline) | 30-day In-hospital Mortality | 467 Participants |
| Balanced Crystalloid | 30-day In-hospital Mortality | 418 Participants |
p-value: <0.0595% CI: [0.73, 0.97]Regression, Logistic