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-SURG will be a large, cluster-randomized, multiple-crossover trial enrolling critically ill patients from the non-medical ICUs at Vanderbilt University from October 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-SURG 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 non-medical intensive care units. All patients admitted to participating non-medical intensive care units at Vanderbilt University medical center who are 18 years or older will be enrolled. The study will occur in one-month blocks. Each participating ICU will be randomized to an initial fluid group (0.9% saline or physiologically balanced isotonic 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 to physiologically balance fluid. The primary endpoint will be major adverse kidney events by 30 days (MAKE30 is the composite of death, new renal replacement therapy, or persistent renal dysfunction at discharge). All aspects of study design, intervention, and data collection will be harmonized with an ongoing, independent study addressing the same question in the medical intensive care unit at Vanderbilt University during a similar study period (SMART-MED). 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 a participating non-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
Recruitment details
The Isotonic Solutions and Major Adverse Events Trial (SMART) was registered for the medical ICU (NCT02444988), which enrolled 5381 patient beginning on June 1 2015, and then for the surgical ICUs (NCT02547779), which enrolled 10,421 patients beginning on October 1 2015. The overall SMART trial enrolled 15,802 patients and ended on April 30 2017.
Participants by arm
| Arm | Count |
|---|---|
| 0.9% Sodium Chloride Patients in an ICU block randomized to saline will receive 0.9% sodium chloride whenever isotonic intravenous crystalloid administration is ordered by the treating provider.
Saline: 0.9% sodium chloride will be used whenever an isotonic crystalloid is ordered | 5,214 |
| Balanced Crystalloids Patients in an ICU block randomized to balanced crystalloids 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 | 5,207 |
| Total | 10,421 |
Baseline characteristics
| Characteristic | Balanced Crystalloids | Total | 0.9% Sodium Chloride |
|---|---|---|---|
| Age, Continuous | 57 years | 57 years | 57 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 | 855 Participants | 1725 Participants | 870 Participants |
| Race (NIH/OMB) White | 4352 Participants | 8696 Participants | 4344 Participants |
| Sex: Female, Male Female | 2108 Participants | 4160 Participants | 2052 Participants |
| Sex: Female, Male Male | 3099 Participants | 6261 Participants | 3162 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 408 / 5,214 | 400 / 5,207 |
| other Total, other adverse events | 0 / 5,214 | 1 / 5,207 |
| serious Total, serious adverse events | 0 / 5,214 | 0 / 5,207 |
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 15,802 patients in the SMART trial, 7,860 were assigned to saline and 7,942 were assigned to balanced crystalloids, of whom 10,421 were enrolled to surgical ICUs with 5,214 assigned to saline and 5,207 assigned to balanced crystalloids.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 0.9% Sodium Chloride | Major Adverse Kidney Event Within 30 Days | 551 Participants |
| Balanced Crystalloids | Major Adverse Kidney Event Within 30 Days | 524 Participants |
p-value: <0.05Regression, 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 | 30-day In-hospital Mortality | 408 Participants |
| Balanced Crystalloids | 30-day In-hospital Mortality | 400 Participants |
p-value: <0.05Regression, Logistic