Clinical trial NCT02444988: Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit
Official title: Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Acute Kidney Injury
Keywords: crystalloid
acute kidney injury
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2015-05-15
Enrollment: 5381
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Admitted to the medical intensive care unit (ICU) at Vanderbilt University Medical Center

Exclusion Criteria:

* Age\<18 years old

Primary outcomes:
measure: Major Adverse Kidney Event Within 30 Days
timeFrame: 30 days after enrollment censored at hospital discharge
Secondary outcomes:
measure: 30-day In-hospital Mortality
timeFrame: 30 days after enrollment censored at hospital discharge
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: Todd W Rice, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J; SAFE TRIPS Investigators. Resuscitation fluid use in critically ill adults: an international cross-sectional study in 391 intensive care units. Crit Care. 2010;14(5):R185. doi: 10.1186/cc9293. Epub 2010 Oct 15.
citation: Yunos NM, Kim IB, Bellomo R, Bailey M, Ho L, Story D, Gutteridge GA, Hart GK. The biochemical effects of restricting chloride-rich fluids in intensive care. Crit Care Med. 2011 Nov;39(11):2419-24. doi: 10.1097/CCM.0b013e31822571e5.
citation: Yunos NM, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17;308(15):1566-72. doi: 10.1001/jama.2012.13356.
citation: Lombardo S, Smith MC, Semler MW, Wang L, Dear ML, Lindsell CJ, Freundlich RE, Guillamondegui OD, Self WH, Rice TW; Isotonic Solutions and Major Adverse Renal Events Trial (SMART) Investigators and Vanderbilt Learning Healthcare System Platform Investigators. Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial. J Neurotrauma. 2022 Sep;39(17-18):1159-1167. doi: 10.1089/neu.2021.0465.
citation: Funke BE, Jackson KE, Self WH, Collins SP, Saunders CT, Wang L, Blume JD, Wickersham N, Brown RM, Casey JD, Bernard GR, Rice TW, Siew ED, Semler MW; SMART Investigators; Pragmatic Critical Care Research Group. Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults. BMC Nephrol. 2021 Feb 5;22(1):54. doi: 10.1186/s12882-021-02236-x.
citation: Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, Coston TD, Felbinger M, Flemmons LN, Hellervik SM, Lindsell CJ, Liu D, McCoin NS, Niswender KD, Slovis CM, Stollings JL, Wang L, Rice TW, Semler MW; Pragmatic Critical Care Research Group. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw Open. 2020 Nov 2;3(11):e2024596. doi: 10.1001/jamanetworkopen.2020.24596.
citation: Brown RM, Wang L, Coston TD, Krishnan NI, Casey JD, Wanderer JP, Ehrenfeld JM, Byrne DW, Stollings JL, Siew ED, Bernard GR, Self WH, Rice TW, Semler MW. Balanced Crystalloids versus Saline in Sepsis. A Secondary Analysis of the SMART Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 15;200(12):1487-1495. doi: 10.1164/rccm.201903-0557OC.
citation: Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584. Epub 2018 Feb 27.
citation: Semler MW, Self WH, Wang L, Byrne DW, Wanderer JP, Ehrenfeld JM, Stollings JL, Kumar AB, Hernandez A, Guillamondegui OD, May AK, Siew ED, Shaw AD, Bernard GR, Rice TW; Isotonic Solutions and Major Adverse Renal Events Trial (SMART) Investigators; Pragmatic Critical Care Research Group. Balanced crystalloids versus saline in the intensive care unit: study protocol for a cluster-randomized, multiple-crossover trial. Trials. 2017 Mar 16;18(1):129. doi: 10.1186/s13063-017-1871-1.