Fluid TherapyFLUIDNCT02721485
Crystalloid FLUID Choices for Resuscitation of Hospital Patients
A study testing Ringer's Lactate and Normal Saline in people with Fluid Therapy, run by Ottawa Hospital Research Institute at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 days to 100 years
- Conditions the study is for
- Fluid Therapy
- What is being tested?
- Ringer's Lactate and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30,000 participants
- Where
- 4 sitesCanada
- Study dates
- Jul 2016to 13 Jan 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 days to 100 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Hamilton General Hospital
Hamilton, Ontario, L8L 2X2
Ottawa Hospital Civic Campus
Ottawa, Ontario, 1053 Carling Ave
The Ottawa Hospital General Campus
Ottawa, Ontario, K1H 8L6
Queensway Carleton Hosptial
Ottawa, Ontario, K2H 8P4
About this study
Official title: Crystalloid FLUID Choices for Resuscitation of Hospital Patients: A Pragmatic Cluster Cross Over Pilot Trial
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.
Read the 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.
- Conditions
- Fluid Therapy
- Being tested
- Ringer's Lactate, Normal Saline
- Keywords
- Ringer's Lactate, Normal Saline, resuscitation fluids, hypovolemia
- Medical subject headings
- Hypovolemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ringer's LactateOther
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.
Normal SalineOther
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 group | Role | What they receive |
|---|---|---|
| Normal Saline | Other | 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. Receives: Other: Ringer's Lactate |
| Ringer's Lactate | Other | 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. Receives: Other: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: adherence to protocol
Compliance defined as at least 80% of the prescribed study fluid being administered in the participating hospitals over the 2, 3-month study periods.
Measured: Up to six months
Feasibility: time to research ethics board approval
Compliance defined as taking no longer than 3 months to achieve
Measured: Up to three months
Feasibility: readiness to initiate protocol
Compliance defined as taking no longer than 3 months after ethics approval
Measured: Up to three months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2016 (estimated)
- Study startJul 2016
- Primary completion13 Jan 2018
- Study completion13 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fluid TherapyStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 30,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lauralyn McIntyre, MD MSc, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02721485
- Sponsor's protocol ID
- 20150619-01H
- Acronym
- FLUID
- Status last verified
- Sep 2018
- First submitted
- 18 Jan 2016
- Last updated
- 1 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No: This is a cluster-randomized crossover study, with the hospital as the unit of randomization. Individual patient data will not be collected.
Publications
McIntyre LA, Fergusson DA, McArdle T, Fox-Robichaud A, English SW, Martin C, Marshall J, Cook DJ, Graham ID, Hawken S, McCartney C, Menon K, Saginur R, Seely A, Stiell I, Thavorn K, Weijer C, Iyengar A, Muscedere J, Forster AJ, Taljaard M; Canadian Critical Care Trials Group. FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate. BMJ Open. 2023 Feb 3;13(2):e067142. doi: 10.1136/bmjopen-2022-067142.
PubMed 36737087McIntyre 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.
PubMed 30139908
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Crystalloid FLUID Choices for Resuscitation of Hospital Patients: A Pragmatic Cluster Cross Over Pilot Trial
- ClinicalTrials.gov ID
- NCT02721485
- Acronym / sponsor ID
- FLUID / 20150619-01H
- Conditions
- Fluid Therapy
- Keywords
- Ringer's Lactate, Normal Saline, resuscitation fluids, hypovolemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30,000 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- 13 Jan 2018 (actual)
- Study completion
- 13 Jan 2018 (actual)
- First posted
- 29 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Normal Saline | Other | Other: Ringer's LactateHalf 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. |
| Ringer's Lactate | Other | Other: Normal SalineHalf 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. |
Who may qualify
- Ages
- 30 days to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ringer's LactateAfter 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 |
| Normal SalineAfter 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. | Other | Ringer's Lactate |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2018.
- Derived from this study: PubMed 36737087McIntyre LA, Fergusson DA, McArdle T, Fox-Robichaud A, English SW, Martin C, Marshall J, Cook DJ, Graham ID, Hawken S, McCartney C, Menon K, Saginur R, Seely A, Stiell I, Thavorn K, Weijer C, Iyengar A, Muscedere J, Forster AJ, Taljaard M; Canadian Critical Care Trials Group. FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate. BMJ Open. 2023 Feb 3;13(2):e067142. doi: 10.1136/bmjopen-2022-067142.
- Derived from this study: PubMed 30139908McIntyre 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.
- Individual participant dataSharing planned: No. This is a cluster-randomized crossover study, with the hospital as the unit of randomization. Individual patient data will not be collected.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lauralyn McIntyre, MD MSc principal investigator
Ottawa Hospital Research Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ringer's Lactate and Normal Saline in people with Fluid Therapy, run by Ottawa Hospital Research Institute at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility: adherence to protocol (time frame: Up to six months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02721485, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2018.