Clinical trial NCT04512950: Crystalloid FLUID Choices for Resuscitation of Hospitalized Patients
Official title: Crystalloid FLUID Choices for Resuscitation of Hospital Patients: A Pragmatic Cluster Cross Over Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fluid Therapy
Keywords: Ringer's Lactate
0.9% saline
Resuscitation
Hypovolemia
Rehydration
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
First posted: 2020-08-14
Enrollment: 43626
Sex: ALL
Minimum age (years): 29
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Cluster Cross Over
Primary purpose: TREATMENT

Brief summary: The aim of the FLUID Trial is to conduct a pragmatic, multi-centre, open label randomized cluster cross-over trial (RCT) to determine whether fluid administration with 0.9% saline as compared to Ringer's lactate decreases death or re-admission to hospital with 90 days of the index admission.

Detailed description: Crystalloid fluids are used extensively for acutely ill patients who are admitted to hospital. Two fluids most commonly used are 0.9% saline and Ringer's Lactate. Both are used to rehydrate patients, restore fluid volume and help stabilize blood pressure and failing organ and both 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). The safety of 0.9% saline is now being questioned due to its high chloride content and its association with the development of hyperchloremic metabolic acidosis. Until recently, the evidence base supporting the superiority of Ringer's Lactate has been derived from observational studies. Two recent pilot studies in critically ill patients comparing 0.9% saline to balanced crystalloid fluids (Ringer's lactate and/or Plasma-Lyte, another balanced crystalloid) did not detect clinical outcome differences between the fluid groups, but the trials were not powered to do so. Furthermore, two multiple period cluster cross-over studies conducted at one institution comparing 0.9% saline to balanced crystalloids (Ringer's lactate and Plasma-Lyte) in the emergency department (ED) and intensive care unit (ICU) found small differences in a composite outcome which included death, requirement for dialysis or persistent renal dysfunction, in favor of balanced crystalloids. In contrast, two large multi-centre randomized trials (BaSICS, n=11 052 and PLUS, n=5037) examined the efficacy of NS as compared with a balanced crystalloid (RL and Plasma-Lyte 148, respectively) on the primary outcome 90-day mortality. Neither of these trials detected a difference in 90-day mortality; in BaSICS, the mortality rate was 22.0% versus 21.8%; in PLUS, mortality was 27.2% versus 26.4%. Renal function did not differ between the fluid groups in either trial, although the PLUS trial was stopped early due to recruitment challenges and insufficient funding during the pandemic. In a systematic review of 13 critical care trials to January 2022 and 35 884 participants, there were no detectable differences in renal function. In low risk of bias trials, there was no significant difference in mortality for the 0.9% saline as compared with balanced crystalloid group (28.2% and 27.9%, respectively; relative risk (RR) 0.96 (95% CI 0.91 to 1.01)), nor renal function. However, authors concluded that there is a high probability balanced crystalloids reduce death since the CIs ranged from a 9% relative reduction to a 1% relative increase in death. Authors and editorialists urge the conduct of large multi-centre randomized trials, with longer-term patient centred outcomes supported by health economic evaluations to provide confirmatory evidence to guide future clinical practice and resource allocation related to these usual care crystalloid fluids.

Small differences in clinical outcomes between crystalloid resuscitation fluids are highly relevant. Furthermore, small absolute differences in important clinical outcomes may translate into substantial savings to hospitals and the health care system. The FLUID trial will determine if there are differences in the clinically important outcomes of death and hospital re-admissions. FLUID is novel in its design because it is a hospital wide pragmatic cluster cross-over comparative effectiveness trial that will be conducted in both academic and community sites which will use provincial health administrative data available through the Institute of Clinical Evaluative Sciences (ICES) for all clinical data collection. Our trial will answer this fundamental fluid resuscitation question and determine if Ringer's Lactate is superior to 0.9% saline at much lower cost in comparison to an individual patient randomized controlled trial (RCT), or even a conventional cluster RCT.

Eligibility criteria: Inclusion Criteria:

● All adult and pediatric patients with an index admission to the participating hospitals during study periods

Exclusion Criteria:

* neonates
* physicians may opt out of the use of the allocated study fluid for a specific patient

Primary outcomes:
measure: Number of participants that died or were readmitted to hospital
timeFrame: 90 days from index hospital admission
Secondary outcomes:
measure: Number of participants that died
timeFrame: 90 days from index hospital admission
measure: Number of participants re-admitted to hospital
timeFrame: 90 days from index hospital admission
measure: Number of participants that required dialysis or continuous renal replacement therapy
timeFrame: 90 days from index hospital admission
measure: Number of participants that required re-intubation in the post anesthetic care unit operative period
timeFrame: Up to 90 days after the initial operation during index hospital admission
measure: Duration of hospitalization
timeFrame: Up to 90 Days from index hospital admission
measure: ED visits
timeFrame: number of index ED visits within 90 days of index hospital admission
measure: Discharged to a facility other than home
timeFrame: 90 days from index hospital admission
measure: Number of patients that required a re-operation
timeFrame: Up to 90 days after the initial operation during index hospital admission
Other outcomes:
measure: Incremental cost, life-year saved, quality-adjusted life-year (QALY)
timeFrame: 90 days from index hospitalization
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: London
country: Canada
facility: University Hospital
state: Ontario
city: London
country: Canada
facility: Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Montfort Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital General Campus
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Civic Campus
state: Ontario
city: Ottawa
country: Canada
facility: Queensway Carleton Hospital
state: Ontario
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Lauralyn McIntyre, MS MHSc
role: PRINCIPAL_INVESTIGATOR
References: