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Crystalloid FLUID Choices for Resuscitation of Hospital Patients (FLUID)

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ClinicalTrials.gov Identifier: NCT02721485
Recruitment Status : Completed
First Posted : March 29, 2016
Last Update Posted : October 1, 2018
Sponsor:
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

Tracking Information
First Submitted Date  ICMJE January 18, 2016
First Posted Date  ICMJE March 29, 2016
Last Update Posted Date October 1, 2018
Actual Study Start Date  ICMJE July 2016
Actual Primary Completion Date January 13, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 3, 2016)
  • Feasibility: adherence to protocol [ Time Frame: Up to six months ]
    Compliance defined as at least 80% of the prescribed study fluid being administered in the participating hospitals over the 2, 3-month study periods.
  • Feasibility: time to research ethics board approval [ Time Frame: Up to three months ]
    Compliance defined as taking no longer than 3 months to achieve
  • Feasibility: readiness to initiate protocol [ Time Frame: Up to three months ]
    Compliance defined as taking no longer than 3 months after ethics approval
Original Primary Outcome Measures  ICMJE
 (submitted: March 22, 2016)
  • Feasibility: adherence to protocol [ Time Frame: At one year from start of study ]
    Compliance defined as at least 80% of the prescribed study fluid being administered in the participating hospitals over the 2, 3-month study periods.
  • Feasibility: time to research ethics board approval [ Time Frame: At one year from start of study ]
    Compliance defined as taking no longer than 3 months to achieve
  • Feasibility: readiness to initiate protocol [ Time Frame: At one year from start of study ]
    Compliance defined as taking no longer than 3 months after ethics approval
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Crystalloid FLUID Choices for Resuscitation of Hospital Patients
Official Title  ICMJE Crystalloid FLUID Choices for Resuscitation of Hospital Patients: A Pragmatic Cluster Cross Over Pilot Trial
Brief Summary Salt fluids are used extensively for acutely ill patients who are admitted to hospital. Two salt fluids commonly used are Normal Saline and Ringer's Lactate. Both are used to rehydrate patients, restore fluid volume and help stabilize blood pressure and failing organs. Both salt fluids have been used for several decades. Until recently, it was thought the fluids are essentially equivalent other than some minor differences related to the concentration of salt components (sodium and chloride) and buffers (Ringer's Lactate has lactate as a buffer). Recent data suggest that salt fluids containing less chloride like the Ringer's Lactate, cause less acid in the blood, less kidney failure, and less death. However, the studies to date are small and weak in their design and it is possible that there are no important differences that affect patients. Hence, the research team will conduct a robust pragmatic clinical trial where several academic and community hospitals will be randomized to use either Ringer's Lactate only or Normal Saline only for a period of three months. The trial will yield high quality and robust data to determine if Ringers Lactate reduces death and re-admissions to hospital. Before embarking on this large-scale trial, it is important to conduct a smaller (pilot) trial to evaluate if the larger trial will be feasible and not too costly. In this small trial involving no less than 4 hospitals, the investigators will determine how well the fluid interventions are adhered to in each hospital, record how long it takes to receive approval from research ethics boards and be ready to start the study. The investigators will also record challenges and develop solutions related to the operations of the trial, and describe important clinical and outcome data essential for the design and planning of the large trial.
Detailed Description

Other than the administration of oxygen, crystalloid resuscitation fluids are the most common intervention administered to the majority of hospitalized patients. These fluids may be used as a life saving measure to re-establish hemodynamic stability, for rehydration, and to replace losses and maintain intravascular volume in the surgical setting. In the province of Ontario alone, approximately 1 million patients per year will receive one or both of these resuscitation fluids during their hospital admission. The two most common usual care resuscitation crystalloid fluids are Normal Saline and Ringer's Lactate and until recently there was no evidence to suggest that one crystalloid fluid was clinically superior to the other. However, the safety of Normal Saline is now being questioned due to its high chloride content and its association with the development of hyperchloremic metabolic acidosis. Studies in healthy volunteers and observational studies in the critically ill and surgical patient populations have associated saline with an increased risk of acute renal injury and requirement for dialysis, post-operative infections, death and increased resource and blood transfusion use. The evidence base is currently weak given that the majority of studies are observational and suffer from methodological weaknesses including confounding by indication, selection bias, and inability to disentangle the effects of a specific fluid due to interaction of co-interventions administered. As such, several authors and editorials have called for adequately powered randomized controlled trials with clinically relevant outcomes to determine if Ringer's Lactate is indeed superior to Normal Saline for resuscitation.

Given their widespread use, small differences in clinical outcomes between crystalloid resuscitation fluids are highly relevant. Furthermore, small absolute differences in important clinical outcomes translate into significant savings to hospitals and the health care system. To illustrate, if death and hospital re-admissions were each reduced by an absolute 0.5%, this would translate to approximately 2500 lives saved and savings of 10 million dollars to the Ontario health care system. Hence, in collaboration with the Canadian Critical Care Trials Group, the Crystalloid FLUID Choices for Hospitalized Patients (FLUID) trial will examine whether Ringer's Lactate as compared to Normal Saline reduces clinically important outcomes such as death, and hospital re-admissions - outcomes that are particularly relevant to hospitals and the health care system. This proposal is a large pragmatic cluster cross-over comparative effectiveness trial that will be conducted in both academic and community centres in Ontario. It will involve waivers of consent and a novel design making use of provincially available health administrative data through the Institute of Clinical Evaluative Sciences (ICES) to facilitate all data collected in the trial. The trial will answer this fundamental fluid resuscitation question with much less cost in comparison to an individual patient randomized controlled trial. It will help build expertise and capacity for future trials of similar design in the province of Ontario and throughout Canada. However, prior to embarking on a large-scale trial, it is imperative to conduct a pilot trial to determine feasibility and optimize the trial design.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Fluid Therapy
Intervention  ICMJE
  • Other: Ringer's Lactate
    After a 1 week run in half of participating hospitals will be crossed over to using Ringer's Lactate as 500 or 1000 ml boluses or infusions as specified by the treating physicians for the second 90-day test period.
  • Other: Normal Saline
    After a 1 week run in half of participating hospitals will be crossed over to using Normal Saline as 500 or 1000 ml boluses or infusions as specified by the treating physicians for the final 90-day test period.
Study Arms  ICMJE
  • Normal Saline
    Half of the hospitals will be allocated to start the 90-day test period using Normal Saline administered as 500 or 1000 ml boluses or infusions as specified by the treating physicians. After a 1 week run out, half of participating hospitals will have up to 2 weeks to switch out stock then will be crossed over to using Ringer's Lactate following a 1 week run in as 500 or 1000 ml boluses or infusions as specified by the treating physicians for the final 90-day test period.
    Intervention: Other: Ringer's Lactate
  • Ringer's Lactate
    Half of the hospitals will be allocated to start the 90-day test period using Ringer's Lactate administered as 500 or 1000 ml boluses or infusions as specified by the treating physicians. After a 1 week run out, half of participating hospitals will have up to 2 weeks to switch out stock then will be crossed over to using Normal Saline following a 1 week run in as 500 or 1000 ml boluses or infusions as specified by the treating physicians in for the final 90-day test period.
    Intervention: Other: Normal Saline
Publications * McIntyre L, Taljaard M, McArdle T, Fox-Robichaud A, English SW, Martin C, Marshall J, Menon K, Muscedere J, Cook DJ, Weijer C, Saginur R, Maybee A, Iyengar A, Forster A, Graham ID, Hawken S, McCartney C, Seely AJ, Stiell IG, Thavorn K, Fergusson DA. FLUID trial: a protocol for a hospital-wide open-label cluster crossover pragmatic comparative effectiveness randomised pilot trial. BMJ Open. 2018 Aug 23;8(8):e022780. doi: 10.1136/bmjopen-2018-022780.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 27, 2018)
30000
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2016)
65000
Actual Study Completion Date  ICMJE January 13, 2018
Actual Primary Completion Date January 13, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients admitted to the participating hospitals for the first time in the last 90 days (index admission) over the duration of the study period.

Exclusion Criteria:

  • Neonates (< 30 days)
  • Physicians may also opt out of the use of the allocated study fluid for individual patients if there is a strong preference to do so.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 100 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02721485
Other Study ID Numbers  ICMJE 20150619-01H
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: This is a cluster-randomized crossover study, with the hospital as the unit of randomization. Individual patient data will not be collected.
Responsible Party Ottawa Hospital Research Institute
Study Sponsor  ICMJE Ottawa Hospital Research Institute
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lauralyn McIntyre, MD MSc Ottawa Hospital Research Institute
PRS Account Ottawa Hospital Research Institute
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP