Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit (SMART-MED)

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ClinicalTrials.gov Identifier: NCT02444988

Recruitment Status : Completed

First Posted : May 15, 2015

Results First Posted : November 25, 2019

Last Update Posted : December 16, 2019

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Sponsor:

Information provided by (Responsible Party):

Todd Rice, Vanderbilt University

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Critical Illness Acute Kidney Injury	Other: 0.9% Saline Other: Physiologically-balanced isotonic crystalloid	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	5381 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Isotonic Solutions and Major Adverse Renal Events Trial in the Medical Intensive Care Unit
Actual Study Start Date :	June 1, 2015
Actual Primary Completion Date :	June 30, 2017
Actual Study Completion Date :	June 30, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Sodium chloride Normosol R PlasmaLyte Plasmalyte 148

Genetic and Rare Diseases Information Center resources: Acute Graft Versus Host Disease

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: 0.9% Saline 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 0.9% Saline will be used whenever an isotonic crystalloid is ordered Other Names: Normal Saline 0.9% sodium chloride
Active Comparator: Physiologically-balanced 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 Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered Other Names: Lactated Ringers Ringer's Lactate Plasma-Lyte© A

Outcome Measures

Primary Outcome Measures :

Major Adverse Kidney Event Within 30 Days [ Time Frame: 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 Outcome Measures :

30-day In-hospital Mortality [ Time Frame: 30 days after enrollment censored at hospital discharge ]
Death before hospital discharge, censored at 30 days after enrollment

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Age<18 years old

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02444988

Locations

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United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37209

Sponsors and Collaborators

Vanderbilt University

Investigators

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Principal Investigator:	Todd W Rice, M.D.	Vanderbilt University

Study Documents (Full-Text)

Documents provided by Todd Rice, Vanderbilt University:

Study Protocol and Statistical Analysis Plan [PDF] June 15, 2017

More Information

Publications:

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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.

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Responsible Party:	Todd Rice, Associate Professor of Medicine, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT02444988
Other Study ID Numbers:	IRB#141349
First Posted:	May 15, 2015 Key Record Dates
Results First Posted:	November 25, 2019
Last Update Posted:	December 16, 2019
Last Verified:	December 2019

Keywords provided by Todd Rice, Vanderbilt University:


crystalloid acute kidney injury

Additional relevant MeSH terms:

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Acute Kidney Injury Critical Illness Renal Insufficiency Kidney Diseases Urologic Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications	Urogenital Diseases Male Urogenital Diseases Disease Attributes Pathologic Processes Plasma-lyte 148 Ophthalmic Solutions Pharmaceutical Solutions

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