Sepsis, Septic ShockPhase 2/3FISSHNCT03677102
Fluids in Septic Shock (FISSH)
A Phase 2/3 study testing higher chloride crystalloid and lower chloride crystalloid in people with Sepsis, Septic Shock, run by McMaster University at 30 sites in 2 countries.
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 and lower chloride crystalloid
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,113 participants
- Where
- 30 sitesin 2 countries
- Study dates
- 9 Sep 2018to 10 Feb 2026
- 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
- patients 16 years or greater who meet all of the following:
- require fluid resuscitation for refractory hypotension (systolic blood pressure <90 mmHg or mean arterial blood pressure<65 mmHg after 1 Litre bolus over 1 hour or less or organ hypo-perfusion (serum lactate >4 mmol/L)
- have a clinical suspicion of infection
- are within 6 hours of hospital admission or critical care response team consultation
- are anticipated to require ICU admission
Who cannot join
- intracranial bleed or intracranial hypertension during the index hospital admission
- 10% of body surface area acute burn injury
- bleeding/hemorrhage as likely cause of hypotension
- a lack of commitment to life support
- have previously enrolled in FISSH, or a confounding trial (e.g. a trial examining the effect of other intravenous fluids in septic shock patients)
- been transferred from another hospital or facility >6 hours since presentation to first hospital
- pre-established end stage renal disease (ESRD) or are receiving hemodialysis (intermittent or continuous) at time of enrolment, or
- been admitted to ICU directly from the operating room or post anaesthetic care unit
Trial locations and contacts
30 sites in 2 countries.
30 sites in 2 countries
Canada28 sites
Lakeridge Health - Ajax Pickering
Ajax, Ontario
Brantford General Hospital
Brantford, Ontario, N3R 1G9
University of Calgary - Foothills Medical Centre
Calgary, Alberta
University of Calgary - Rockyview General Hospital
Calgary, Alberta
Grey Nuns Community Hospital
Edmonton, Alberta
Halifax Infirmary
Halifax, Nova Scotia
Victoria General
Halifax, Nova Scotia
St Joseph's Healthcare
Hamilton, Ontario, L8N 4A6
Juravinski Hospital-Hamilton Health Sciences
Hamilton, Ontario, L8V 1C1
Hamilton General Hospital
Hamilton, Ontario
Kingston General Hospital
Kingston, Ontario, K7L 2V7
London Health Sciences Centre - Victoria Hospital
London, Ontario, N6A 5W9
London Health Sciences - University Hospital
London, Ontario
Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal
Montreal, Quebec, H4J 1C5
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec
Lakeridge Health
Oshawa, Ontario, L1G 2B9
CHU de Québec Université Laval
Québec, Quebec, G1J 1Z4
Royal University Hospital
Saskatoon, Saskatchewan
St Paul's Hospital
Saskatoon, Saskatchewan
Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke
Sherbrooke, Quebec, J1H 5N4
Niagara Health, St Catharines Site
St. Catharines, Ontario, L2S 0A9
Cape Breton Regional Hospital
Sydney, Nova Scotia
Unity Health (St. Michael's Hospital)
Toronto, Ontario, M5B 1W8
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Sunnybrook Health Sciences Centre
Toronto, Ontario
Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)
Trois-Rivières, Quebec
Windsor Regional Hospital - Ouellette Campus
Windsor, Ontario
Windsor Regional Hospital -Metropolitan Campus
Windsor, Ontario
Saudi Arabia2 sites
King Abdulaziz Medical City- Riyadh (KAMC-R)
Riyadh
King Faisal Specialist Hospital & Research Centre
Riyadh
About this study
Official title: Fluids in Septic Shock (FISSH): a 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 randomized controlled trial (RCT) evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. This trial will directly compare 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 that 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). This trial will build on the earlier pilot, phase 1 study and will look at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU. This 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, lower chloride crystalloid
- 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 (chloride concentration 154 mmol/L)
lower chloride crystalloidOther
Ringer's Lactate (chloride concentration 110 mmol/L)
| Study group | Role | What they receive |
|---|---|---|
| higher chloride solutions | Active comparator | higher chloride crystalloid (Normal saline - chloride concentration 154 mmol/L) Receives: Other: higher chloride crystalloid |
| lower chloride solutions | Active comparator | lower chloride crystalloid (Ringer's lactate - chloride concentration 110 mmol/L) Receives: Other: lower chloride crystalloid |
What is being measured
The primary outcome is the main question the study is designed to answer.
30 day mortality
Investigators expect that if a difference in survival is demonstrated that this will be evident within 30 days.
Measured: up to 30 days
Secondary outcomes (13)
Hospital mortality
Investigators expect that if a difference in survival is demonstrated, that this will be evident within 30 days.
Measured: up to 30 days
ICU mortality
Investigators expect that if a difference in survival is demonstrated, that this will be evident within 30 days.
Measured: up to 30 days
Hospital length of stay
length of hospital stay up to 30 days
Measured: up to 30 days
ICU length of stay
length of ICU stay up to 30 days
Measured: up to 30 days
Acute Kidney Injury
Acute kidney injury - development of stage 2 or worse acute kidney injury (AKI) according to KDIGO guidelines17 based strictly on serum creatinine criteria. Stage 2 AKI is defined as serum creatinine 2.0-2.9 times baseline. For the purposes of analysis, baseline creatinine will be an outpatient reading within 365 days of the current admission date. If multiple pre-hospitalization values are available, the value closest to the date of hospital admission will be used. If an outpatient pre-hospitalization value is not available, the lowest creatinine value obtained during the current hospitalization will be considered baseline 18.
Measured: up to 30 days
Ventilator free days
defined as cumulative number of days alive without receiving greater than or equal to 2 hours of mechanical ventilation, censored at 30 days; patients who die prior to 30 days will be assigned -1
Measured: up to 30 days
Vasopressor-free days
defined as the cumulative number of days alive without requiring greater than or equal to 2 hours of intravenous vasopressor support, censored at 30 days; patients who die prior to 30 days will be assigned -1
Measured: up to 30 days
Change in organ failure score
calculated using the SOFA score (sequential organ failure assessments score) , defined as the net change in SOFA from day 1 until ICU discharge or death minimum 0, maximum 24 higher score is worse
Measured: up to 30 days
hyperchloremia
the number of patients with hyperchloremia
Measured: up to 30 days
Hyperkalemia
the number of patients with hyperkalemia
Measured: up to 30 days
Hypernatremia
the number of patients with hypernatremia
Measured: up to 30 days
Acidosis
the number of patients with acidosis
Measured: up to 30 days
Serious adverse events related to study fluid
critically ill patients are admitted to the ICU for life-sustaining therapies and medical complications are likely to occur in this population consistent with severity of illness. Due to these unique morbidity and mortality expectations, we don't collect generic adverse events but instead focus on study-related SAEs that the attending physician believes related to the study fluid with plausible time sequence and biological plausibility
Measured: 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 posted19 Sep 2018
- Study start9 Sep 2018
- Primary completion2 Feb 2026
- Study completion10 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sepsis, Septic ShockStudies of the same condition, open and under way.
- 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
- 1,113 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Bram Rochwerg, MSc,MD,FRCPC, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03677102
- Sponsor's protocol ID
- 1515
- Acronym
- FISSH
- Status last verified
- Feb 2026
- First submitted
- 27 Aug 2018
- Last updated
- 27 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fluids in Septic Shock (FISSH): a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT03677102
- Acronym / sponsor ID
- FISSH / 1515
- Conditions
- Sepsis, Septic Shock
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,113 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- The Physicians' Services Incorporated Foundation, Canadian Institutes of Health Research (CIHR)
- Study start
- 9 Sep 2018 (actual)
- Primary completion
- 2 Feb 2026 (actual)
- Study completion
- 10 Feb 2026 (actual)
- First posted
- 19 Sep 2018 (actual)
- 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 randomized controlled trial (RCT) evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. This trial will directly compare 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 that 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). This trial will build on the earlier pilot, phase 1 study and will look at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU. This 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 crystalloidhigher chloride crystalloid (Normal saline - chloride concentration 154 mmol/L) |
| lower chloride solutions | Active comparator | Other: lower chloride crystalloidlower chloride crystalloid (Ringer's lactate - chloride concentration 110 mmol/L) |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- patients 16 years or greater who meet all of the following:
- require fluid resuscitation for refractory hypotension (systolic blood pressure <90 mmHg or mean arterial blood pressure<65 mmHg after 1 Litre bolus over 1 hour or less or organ hypo-perfusion (serum lactate >4 mmol/L)
- have a clinical suspicion of infection
- are within 6 hours of hospital admission or critical care response team consultation
- are anticipated to require ICU admission
Key exclusion criteria (8 listed)
- intracranial bleed or intracranial hypertension during the index hospital admission
- 10% of body surface area acute burn injury
- bleeding/hemorrhage as likely cause of hypotension
- a lack of commitment to life support
- have previously enrolled in FISSH, or a confounding trial (e.g. a trial examining the effect of other intravenous fluids in septic shock patients)
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 (chloride concentration 154 mmol/L) | Other | higher chloride solutions |
| lower chloride crystalloidRinger's Lactate (chloride concentration 110 mmol/L) | Other | lower chloride solutions |
Primary outcome
30 day mortality
Time frame: up to 30 days
Investigators expect that if a difference in survival is demonstrated that this will be evident within 30 days.
13 secondary outcomes
Hospital mortality
Time frame: up to 30 days
ICU mortality
Time frame: up to 30 days
Hospital length of stay
Time frame: up to 30 days
ICU length of stay
Time frame: up to 30 days
Acute Kidney Injury
Time frame: up to 30 days
Ventilator free days
Time frame: up to 30 days
Vasopressor-free days
Time frame: up to 30 days
Change in organ failure score
Time frame: up to 30 days
hyperchloremia
Time frame: up to 30 days
Hyperkalemia
Time frame: up to 30 days
Hypernatremia
Time frame: up to 30 days
Acidosis
Time frame: up to 30 days
Serious adverse events related to study fluid
Time frame: 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 27 Feb 2026.
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RecruitingObservational study
Clinical Value of EMR3 in Sepsis Diagnosis, Monitoring, and Prognosis: A Multicenter Prospective Observational Study
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A Trial of Adjunctive Fludrocortisone (50mcg, 100mcg or Placebo) in Critically Ill Patients With Septic Shock Receiving Hydrocortisone, Evaluating Survival and Functional Recovery and the Influence of Transcriptomic Response
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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.
Bram Rochwerg, MSc,MD,FRCPC principal investigator
McMaster University
30 sites in 2 countries: 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 and lower chloride crystalloid in people with Sepsis, Septic Shock, run by McMaster University at 30 sites in 2 countries.
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 5 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 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Canada, Saudi Arabia. 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?
30 day mortality (time frame: up to 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Feb 2026; AzTrials last refreshed its copy on 30 Oct 2026.