NCT02444988

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
5,381

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jun 2015

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 11, 2015

Completed
4 days until next milestone

First Posted

Study publicly available on registry

May 15, 2015

Completed
17 days until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2017

Completed
2.4 years until next milestone

Results Posted

Study results publicly available

November 25, 2019

Completed
Last Updated

December 16, 2019

Status Verified

December 1, 2019

Enrollment Period

2.1 years

First QC Date

May 11, 2015

Results QC Date

August 19, 2019

Last Update Submit

December 5, 2019

Conditions

Critical IllnessAcute Kidney Injury

Keywords

crystalloidacute kidney injury

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (1)

  • 30-day In-hospital Mortality

    30 days after enrollment censored at hospital discharge

Study Arms (2)

0.9% Saline

ACTIVE COMPARATOR

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

Physiologically-balanced

ACTIVE COMPARATOR

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

Interventions

0.9% SalineOTHER

0.9% Saline will be used whenever an isotonic crystalloid is ordered

Also known as: Normal Saline, 0.9% sodium chloride
0.9% Saline
Physiologically-balanced isotonic crystalloidOTHER

Lactated Ringers or Plasma-Lyte© A will be used whenever an isotonic crystalloid is ordered

Also known as: Lactated Ringers, Ringer's Lactate, Plasma-Lyte© A
Physiologically-balanced

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • Age\<18 years old

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37209, United States

Location

Related Publications (9)

  • 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.

    PMID: 20950434BACKGROUND

  • 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.

    PMID: 21705897BACKGROUND

  • 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.

    PMID: 23073953BACKGROUND

  • 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.

    PMID: 35443809DERIVED

  • 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.

    PMID: 33546622DERIVED

  • 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.

    PMID: 33196806DERIVED

  • 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.

    PMID: 31454263DERIVED

  • 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.

    PMID: 29485925DERIVED

  • 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.

    PMID: 28302179DERIVED

MeSH Terms

Conditions

Critical IllnessAcute Kidney Injury

Interventions

Saline SolutionSodium ChlorideRinger's Lactate

Condition Hierarchy (Ancestors)

Disease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical PreparationsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium Compounds

Results Point of Contact

Title
Matthew W. Semler, MD, MSc
Organization
Vanderbilt University Medical Center
matthew.w.semler@vumc.org
(615) 322-3412

Study Officials

  • Todd W Rice, M.D.

    Vanderbilt University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Medicine

Study Record Dates

First Submitted

May 11, 2015

First Posted

May 15, 2015

Study Start

June 1, 2015

Primary Completion

June 30, 2017

Study Completion

June 30, 2017

Last Updated

December 16, 2019

Results First Posted

November 25, 2019

Record last verified: 2019-12

Locations

US(1)