SepsisPhase 2/3FISSHNCT02748382
Fluids in Sepsis and Septic Shock
A Phase 2/3 study testing higher chloride crystalloid, higher chloride albumin and lower chloride crystalloid in people with Sepsis and Septic Shock, run by McMaster University at 2 sites in Canada.
Trial summary
Despite evidence of the physiologic benefits and possible lower mortality associated with low chloride solutions, normal saline remains the most wildly used fluid in the world. Given uncertainty about the impact of lower chloride versus higher chloride solutions on mortality, it is unlikely that clinical practice will… Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Sepsis, Septic Shock
- What is being tested?
- higher chloride crystalloid, higher chloride albumin and lower chloride crystalloid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesCanada
- Study dates
- 18 Aug 2016to 19 Aug 2017
- Phase
- Phase 2/3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient must be at least 16 years of age
- Within 6 hours from presentation to hospital or activation of MET/RACE team to ward
- Requires fluid resuscitation for refractory hypotension OR organ hypoperfusion
- refractory hypotension definition - sBP <90 OR MAP <65 after 1L bolus given over 1 hour or less
- organ hypoperfusion - lactate >4
- Suspected source of infection as etiology for hypotension
- Treating physician anticipates patient will require admission to ICU
Who cannot join
- Intracranial bleed or intracranial hypertension during this hospital admission
- Acute burn injury (>10% body surface area)
- Bleeding/hemorrhage as likely cause of hypotension
- Plan in place to change goals of care to palliation
- Previously enrolled in FISSH
- Previously enrolled in confounding trial
- Transfer from another hospital or facility
- Admission directly from the operating room or PACU
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Juravinski Hospital-Hamilton Health Sciences
Hamilton, Ontario, L8V 1C1
Centre Hospitalier Universitaire de Sherbrooke
Sherbrooke, Quebec, J1H 3H5
About this study
Official title: Fluids in Sepsis and Septic Shock: A Pilot Randomized Controlled Trial
Despite evidence of the physiologic benefits and possible lower mortality associated with low chloride solutions, normal saline remains the most wildly used fluid in the world. Given uncertainty about the impact of lower chloride versus higher chloride solutions on mortality, it is unlikely that clinical practice will change without new and direct RCT evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. The proposed feasibility RCT will investigate the feasibility of a large-scale trial directly comparing low chloride versus normal chloride for resuscitation in septic shock on patient-important outcomes such as mortality and AKI.
Read the detailed description
Severe infection can lead to many complications within the human body including low blood pressure, which is called septic shock. The main treatments for septic shock are intravenous antibiotics and intravenous fluid.
There are many different intravenous fluids available for doctors to use. Each one of these fluids has potential advantages as well as potential disadvantages. Doctors will often look at many things when deciding which fluid to give including the results of bloodwork and the clinical characteristics of the patients themselves. There is limited direction from research studies taht using one fluid type is better than another. Some preliminary research in the field has suggested that one specific electrolyte, call chloride, may be harmful when given to patients in high concentrations. Animal research has shown that the administration of high chloride fluids may be harmful to the lungs, kidneys, gastrointestinal and muscle cells. Some intravenous fluids have higher concentrations of chloride than others.
The investigators plan to study the impact of giving patients with severe infection intravenous fluids with either a high chloride concentration (normal saline or high chloride albumin) or a low chloride concentration (Ringers Lactate or low chloride albumin). Although, the investigators plan for a larger trial looking at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU the investigators think it's important to start with a feasibility study. If the investigators are able to show a larger trial is feasible then the investigators will apply for further funding and use the lessons learned from this pilot to optimize the larger study. The larger study has the potential to guide the care of critically ill patients with infection worldwide.
- Conditions
- Sepsis, Septic Shock
- Being tested
- higher chloride crystalloid, higher chloride albumin, lower chloride crystalloid, lower chloride albumin
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
higher chloride crystalloidOther
Normal saline
higher chloride albuminOther
5% Octalbin
lower chloride crystalloidOther
Ringers Lactate
lower chloride albuminOther
5% Plasbumin
| Study group | Role | What they receive |
|---|---|---|
| higher chloride solutions | Active comparator | higher chloride crystalloid (Normal saline) higher chloride albumin (5% Octalbin) Receives: Other: higher chloride crystalloid; Other: higher chloride albumin |
| lower chloride solutions | Active comparator | lower chloride crystalloid (Ringer's lactate) lower chloride albumin (5% Plasbumin) Receives: Other: lower chloride crystalloid; Other: lower chloride albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Consent Rate
Consent rate will be considered adequate if greater than 70% of substitute decision makers (SDMs) or patients when approached for consent choose to participate.
Measured: 12 months
Patient Recruitment
Successful recruitment will be defined as achieving enrolment of 50 patients over the 12-month study period. This works out to approximately 1 patient/center/month. Once the pilot trial begins, the screening logs will be reviewed at all three study centers by the study steering committee on a monthly basis. We will record exclusions and reasons for physician refusals.
Measured: 12 months
Protocol Adherence
Successful adherence will be defined as patients receiving at least 75% study fluid of all intravenous fluid that is administered in the ICU excluding blood products and medication infusions.
Measured: 12 months
Secondary outcomes (6)
Hospital length of stay
Measured: Duration of index hospital stay censored at 90 days.
Hospital mortality
Mortality during index hospitalization censored at 90 days.
Measured: hospital stay or up to 90 days
Renal replacement therapy use
Any use of renal replacement therapy including hemodialysis, peritoneal dialysis or continuous renal replacement. This will be reported as a dichotomous outcome.
Measured: RRT use during index hospital stay censored at 90 days.
ICU length of stay
Measured: Duration of index ICU stay censored at 90 days.
Hyperkalemia
Number of participants with any serum potassium value >5mmol/L.
Measured: Incidence during index ICU stay or up to 30 days
Acidosis
Number of participants with any serum pH <7.20
Measured: Incidence during index ICU stay or up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2016 (estimated)
- Study start18 Aug 2016
- Primary completion19 Aug 2017
- Study completion19 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02748382
- Sponsor's protocol ID
- 1636
- Acronym
- FISSH
- Status last verified
- Aug 2018
- First submitted
- 8 Apr 2016
- Last updated
- 29 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Rochwerg B, Millen T, Austin P, Zeller M, D'Aragon F, Jaeschke R, Masse MH, Mehta S, Lamontagne F, Meade M, Guyatt G, Cook DJ; Canadian Critical Care Trials Group. Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial. BMJ Open. 2017 Jul 20;7(7):e017602. doi: 10.1136/bmjopen-2017-017602.
PubMed 28729329
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluids in Sepsis and Septic Shock: A Pilot Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02748382
- Acronym / sponsor ID
- FISSH / 1636
- Conditions
- Sepsis, Septic Shock
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Hamilton Health Sciences Corporation
- Study start
- 18 Aug 2016 (actual)
- Primary completion
- 19 Aug 2017 (actual)
- Study completion
- 19 Aug 2017 (actual)
- First posted
- 22 Apr 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.
Despite evidence of the physiologic benefits and possible lower mortality associated with low chloride solutions, normal saline remains the most wildly used fluid in the world. Given uncertainty about the impact of lower chloride versus higher chloride solutions on mortality, it is unlikely that clinical practice will change without new and direct RCT evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. The proposed feasibility RCT will investigate the feasibility of a large-scale trial directly comparing low chloride versus normal chloride for resuscitation in septic shock on patient-important outcomes such as mortality and AKI.
Detailed description
Severe infection can lead to many complications within the human body including low blood pressure, which is called septic shock. The main treatments for septic shock are intravenous antibiotics and intravenous fluid.
There are many different intravenous fluids available for doctors to use. Each one of these fluids has potential advantages as well as potential disadvantages. Doctors will often look at many things when deciding which fluid to give including the results of bloodwork and the clinical characteristics of the patients themselves. There is limited direction from research studies taht using one fluid type is better than another. Some preliminary research in the field has suggested that one specific electrolyte, call chloride, may be harmful when given to patients in high concentrations. Animal research has shown that the administration of high chloride fluids may be harmful to the lungs, kidneys, gastrointestinal and muscle cells. Some intravenous fluids have higher concentrations of chloride than others.
The investigators plan to study the impact of giving patients with severe infection intravenous fluids with either a high chloride concentration (normal saline or high chloride albumin) or a low chloride concentration (Ringers Lactate or low chloride albumin). Although, the investigators plan for a larger trial looking at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU the investigators think it's important to start with a feasibility study. If the investigators are able to show a larger trial is feasible then the investigators will apply for further funding and use the lessons learned from this pilot to optimize the larger study. The larger study has the potential to guide the care of critically ill patients with infection worldwide.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| higher chloride solutions | Active comparator | Other: higher chloride crystalloid, Other: higher chloride albuminhigher chloride crystalloid (Normal saline) higher chloride albumin (5% Octalbin) |
| lower chloride solutions | Active comparator | Other: lower chloride crystalloid, Other: lower chloride albuminlower chloride crystalloid (Ringer's lactate) lower chloride albumin (5% Plasbumin) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patient must be at least 16 years of age
- Within 6 hours from presentation to hospital or activation of MET/RACE team to ward
- Requires fluid resuscitation for refractory hypotension OR organ hypoperfusion
- Suspected source of infection as etiology for hypotension
- Treating physician anticipates patient will require admission to ICU
Key exclusion criteria (8 listed)
- Intracranial bleed or intracranial hypertension during this hospital admission
- Acute burn injury (>10% body surface area)
- Bleeding/hemorrhage as likely cause of hypotension
- Plan in place to change goals of care to palliation
- Previously enrolled in FISSH
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 |
|---|---|---|
| higher chloride crystalloidNormal saline | Other | higher chloride solutions |
| higher chloride albumin5% Octalbin | Other | higher chloride solutions |
| lower chloride crystalloidRingers Lactate | Other | lower chloride solutions |
| lower chloride albumin5% Plasbumin | Other | lower chloride solutions |
Primary outcome
Consent Rate
Time frame: 12 months
Consent rate will be considered adequate if greater than 70% of substitute decision makers (SDMs) or patients when approached for consent choose to participate.
Patient Recruitment
Time frame: 12 months
Successful recruitment will be defined as achieving enrolment of 50 patients over the 12-month study period. This works out to approximately 1 patient/center/month. Once the pilot trial begins, the screening logs will be reviewed at all three study centers by the study steering committee on a monthly basis. We will record exclusions and reasons for physician refusals.
Protocol Adherence
Time frame: 12 months
Successful adherence will be defined as patients receiving at least 75% study fluid of all intravenous fluid that is administered in the ICU excluding blood products and medication infusions.
6 secondary outcomes
Hospital length of stay
Time frame: Duration of index hospital stay censored at 90 days.
Hospital mortality
Time frame: hospital stay or up to 90 days
Renal replacement therapy use
Time frame: RRT use during index hospital stay censored at 90 days.
ICU length of stay
Time frame: Duration of index ICU stay censored at 90 days.
Hyperkalemia
Time frame: Incidence during index ICU stay or up to 30 days
Acidosis
Time frame: Incidence during index ICU stay or up to 30 days
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 29 Aug 2018.
- Derived from this study: PubMed 28729329Rochwerg B, Millen T, Austin P, Zeller M, D'Aragon F, Jaeschke R, Masse MH, Mehta S, Lamontagne F, Meade M, Guyatt G, Cook DJ; Canadian Critical Care Trials Group. Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial. BMJ Open. 2017 Jul 20;7(7):e017602. doi: 10.1136/bmjopen-2017-017602.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing higher chloride crystalloid, higher chloride albumin and lower chloride crystalloid in people with Sepsis and Septic Shock, run by McMaster University at 2 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 7 inclusion and 8 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 29 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Consent Rate (time frame: 12 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 NCT02748382, which also lists 1 linked publication.
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 29 Aug 2018.