Severe Sepsis or Septic ShockPhase 4PITSTOPNCT03068741
Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
A Phase 4 study testing Comparison 1: Prehospital Ceftriaxone, Comparison 2: Liberal fluids and Comparison 2: Conservative fluids in people with Severe Sepsis or Septic Shock, run by Dr. Damon Scales at 4 sites in Canada.
Trial summary
Sepsis occurs when a serious infection - most commonly infection of the lungs, urinary system, or blood - leads to acute organ failure. It is a common, expensive, and frequently lethal condition. A growing body of evidence suggests that early recognition and treatment of sepsis can improve survival. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Sepsis or Septic Shock
- What is being tested?
- Comparison 1: Prehospital Ceftriaxone, Comparison 2: Liberal fluids and Comparison 2: Conservative fluids
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,061 participants
- Where
- 4 sitesCanada
- Study dates
- 23 Mar 2020to 17 Nov 2025
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with Sepsis, defined as (all 3 must be present): i) Paramedic suspects possible infection: e.g. suspected pneumonia, urinary tract infection, skin infection, bone and joint infection, intra-abdominal infection, meningitis ii) Presence of fever: Temperature ≥ 38.0°C measured by paramedic or history of fever during previous 24 hours iii) Presence of hypotension: Systolic blood pressure < 100mmHg
- Age ≥ 18 years
Who cannot join
- Post cardiac arrest
- Suspected ST-segment elevation myocardial infarction (STEMI)
- Suspected acute cerebrovascular accident (CVA)
- Acute severe trauma
- Obvious severe non-traumatic bleeding
- Signs of fluid overload
Show all 12Show fewer
- Suspected acute congestive heart failure (CHF)
- Known Clostridium difficile infection within the last 6 weeks
- Known pregnancy or breastfeeding
- Known allergy or sensitivity to penicillin or cephalosporin
- Known to be receiving oral or subcutaneous anticoagulants or low molecular weight heparin
- Paramedic is unable to identify patient by first and last name and/or health card number
Trial locations and contacts
4 sites in 1 country.
Canada4 sites
Halton Region Paramedic Services
Toronto, Ontario
Peel Region Paramedic Services
Toronto, Ontario
Toronto Paramedic Services
Toronto, Ontario
York Region Paramedic Services
Toronto, Ontario
About this study
Sepsis occurs when a serious infection - most commonly infection of the lungs, urinary system, or blood - leads to acute organ failure. It is a common, expensive, and frequently lethal condition. A growing body of evidence suggests that early recognition and treatment of sepsis can improve survival.
Unfortunately, many patients with sepsis do not receive key therapies until physicians working in Emergency Departments have assessed them - often introducing marked delays. It is estimated that one-half of patients with sepsis are treated and transported to hospital by paramedics. This allows paramedics a unique opportunity to provide early treatment at the initial point of patient contact, thereby decreasing the time to treatment for these critically ill patients. This randomized controlled trial will evaluate whether prompt recognition followed by early antibiotics and/or intravenous fluids delivered by paramedics in the field leads to improved survival, compared to usual care, for patients who are transported to the hospital with sepsis.
Read the detailed description
The ultimate goal of this research program is to evaluate a fundamental change in the delivery of sepsis care. Currently, patients with severe sepsis do not receive key evidence-based therapies until they have been assessed in emergency departments - often introducing considerable delays. This research tests whether integrating paramedics directly into a chain-of-survival for sepsis will improve outcomes for these critically ill patients. In essence, this research seeks to break down silos of care, delivering sepsis treatments based on when they are needed, rather than on where the patient is physically located. If the trial is positive, the results will have broad implications for other health systems by showing that prehospital identification and treatment of sepsis increases the number of patients that survive this life-threatening condition. If the trial fails to demonstrate effectiveness of prehospital sepsis treatments, it will ensure that resources are not needlessly invested in large-scale implementations of paramedic sepsis protocols, as has been done in several other jurisdictions. A lack of benefit would also cast doubt on the observational data suggesting that early antibiotics are important, and suggest a more restrained approach to empiric antibiotic therapy.
- Conditions
- Severe Sepsis or Septic Shock
- Being tested
- Comparison 1: Prehospital Ceftriaxone, Comparison 1: Placebo, Comparison 2: Liberal fluids, Comparison 2: Conservative fluids
- 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.
Comparison 1: Prehospital CeftriaxoneDrug
Also called Ceftriaxone
Paramedics will administer 1g of intramuscular ceftriaxone.
Comparison 1: PlaceboDrug
Also called 0.9% saline for injection
Paramedics will administer an identical volume of reconstituted intramuscular placebo.
Comparison 2: Liberal fluidsDrug
Also called intravenous saline (0.9%) for injection
Paramedics will administer up to 2 litres of intravenous saline (0.9%) to all patients regardless of systolic blood pressure, and reassessing this infusion after each 250ml are infused.
Comparison 2: Conservative fluidsDrug
Also called intravenous saline (0.9%) for injection
Paramedics will administer intravenous saline (0.9%) according to the Medical Directive, which allows for infusion of fluids if systolic blood pressure is <90mmHg and continued until systolic blood pressure is >=100mmHg.
| Study group | Role | What they receive |
|---|---|---|
| Comparison 1: Prehospital Ceftriaxone | Active comparator | 1g of Ceftriaxone will be administered by immediate intramuscular (IM) injection. The drug is provided in a sterile and completely covered vial as a white, odourless powder Receives: Drug: Comparison 1: Prehospital Ceftriaxone |
| Comparison 1: Placebo | Placebo comparator | The placebo is provided in a sterile and completely covered vial. Receives: Drug: Comparison 1: Placebo |
| Comparison 2: Liberal fluids | Experimental | Paramedics will administer up to 2 litres of intravenous 0.9% saline solution to all participants in this arm regardless of blood pressure, reassessing for signs of volume overload after each 250ml. Receives: Drug: Comparison 2: Liberal fluids |
| Comparison 2: Conservative fluids | Active comparator | Paramedics will administer 0.9% saline solution to participants who have systolic blood pressure <90mmHg, and will only continue the infusion until the systolic blood pressure is >=100mmHg. Receives: Drug: Comparison 2: Conservative fluids |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary outcome: mortality prior to hospital discharge to day 90.
Dichotomous outcome reported as percentage
Measured: 90 days
Secondary outcomes (16)
Mortality at 90 days after enrollment
Dichotomous outcome reported as percentage
Measured: 90 days after enrollment
Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis
Dichotomous outcome reported as percentage
Measured: 24 hours
Organ dysfunction during hospitalization (mechanical ventilation)
Dichotomous outcome reported as percentage
Measured: until hospital discharge, measured up to maximum of day 90
duration of hospital admission (if any)
Measured in days from time of randomization
Measured: until hospital discharge, measured up to maximum of day 90
duration of first ICU admission (if any)
Measured in days from time of randomization
Measured: until ICU discharge, measured up to maximum of day 90
Proportion of patients with positive blood cultures obtained in hospital
Dichotomous outcome reported as percentage
Measured: 24 hours
Microbiology results (if any)
Descriptive outcome, reported as frequency distribution of positive culture results
Measured: 24 hours
Proportion of patients receiving antibiotics within first 24 hours of hospitalization
Dichotomous outcome reported as percentage
Measured: 24 hours
Frequency distribution and mean time to first dose of antibiotics (if any) within first 24 hours of hospitalization
Measured in hours from time of randomization
Measured: 24 hours
Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization
measured in milliliters
Measured: 24 hours
Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)
measured in milliliters
Measured: 24 hours
Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray
Dichotomous outcome reported as percentage
Measured: during transport and on initial chest x-ray (if completed)
Proportion of patients with blood, urine, sputum cultures that grow organisms resistant to ceftriaxone
Dichotomous outcome reported as percentage
Measured: 24 hours
Proportion of patients diagnosed with sepsis or infection by emergency department physician
Dichotomous outcome reported as percentage
Measured: during admission
Proportion of hospitalized patients who grow any antibiotic-resistant organism (methicilin resistant S. aureus, Clostridium difficile, extended beta-lactamase resistant organisms)
Dichotomous outcome reported as percentage
Measured: during admission
Proportion of patients with anaphylaxis or suspected allergic reactions to study medication
Dichotomous outcome reported as percentage
Measured: during admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start23 Mar 2020
- Primary completion17 Nov 2025
- Study completion17 Nov 2025
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 Severe Sepsis or 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- This is a 2x2 factorial RCT, with simultaneous randomization of individual patients into 2 randomized controlled trials. The first RCT compares administration of 1g of intramuscular ceftriaxone versus placebo. In this RCT, participants, care providers, investigators, and outcome assessors will all be masked to the treatment allocation. The second RCT compares a liberal fluid resuscitation (up to 2litres of intravenous 0.9% saline) versus conventional resuscitation (administration of intravenous 0.9% saline, started only when systolic blood pressure is \<90mmHg and only continued until systolic blood pressure is \>= 100mmHg). In this RCT, only participants and outcome assessors will be masked.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,061 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Damon Scales
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute
- Responsible party
- Sponsor-investigator, Dr. Damon Scales, Sunnybrook Health Sciences Centre
- Investigators
- Damon Scales, MD PhD FRCPC, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068741
- Sponsor's protocol ID
- The PITSTOP RCT
- Acronym
- PITSTOP
- Status last verified
- Apr 2026
- First submitted
- 6 Feb 2017
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Scales DC, Rogowsky A, Burry L, Christenson J, Daneman N, Drennan IR, Hillier M, Jenneson S, Klein G, Mazzulli T, Moran P, Morris AM, Morrison LJ, Pinto R, Rubenfeld GD, Seymour CW, Stenstrom R, Verbeek PR, Cheskes S. Prehospital antibiotics and intravenous fluids for patients with sepsis: protocol for a 2x2 factorial randomised controlled trial. BMJ Open. 2025 May 27;15(5):e104257. doi: 10.1136/bmjopen-2025-104257.
PubMed 40436458
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
- ClinicalTrials.gov ID
- NCT03068741
- Acronym / sponsor ID
- PITSTOP / The PITSTOP RCT
- Conditions
- Severe Sepsis or Septic Shock
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2,061 participants (actual)
- Lead sponsor
- Dr. Damon ScalesUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute
- Study start
- 23 Mar 2020 (actual)
- Primary completion
- 17 Nov 2025 (actual)
- Study completion
- 17 Nov 2025 (actual)
- First posted
- 3 Mar 2017 (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.
Sepsis occurs when a serious infection - most commonly infection of the lungs, urinary system, or blood - leads to acute organ failure. It is a common, expensive, and frequently lethal condition. A growing body of evidence suggests that early recognition and treatment of sepsis can improve survival.
Unfortunately, many patients with sepsis do not receive key therapies until physicians working in Emergency Departments have assessed them - often introducing marked delays. It is estimated that one-half of patients with sepsis are treated and transported to hospital by paramedics. This allows paramedics a unique opportunity to provide early treatment at the initial point of patient contact, thereby decreasing the time to treatment for these critically ill patients. This randomized controlled trial will evaluate whether prompt recognition followed by early antibiotics and/or intravenous fluids delivered by paramedics in the field leads to improved survival, compared to usual care, for patients who are transported to the hospital with sepsis.
Detailed description
The ultimate goal of this research program is to evaluate a fundamental change in the delivery of sepsis care. Currently, patients with severe sepsis do not receive key evidence-based therapies until they have been assessed in emergency departments - often introducing considerable delays. This research tests whether integrating paramedics directly into a chain-of-survival for sepsis will improve outcomes for these critically ill patients. In essence, this research seeks to break down silos of care, delivering sepsis treatments based on when they are needed, rather than on where the patient is physically located. If the trial is positive, the results will have broad implications for other health systems by showing that prehospital identification and treatment of sepsis increases the number of patients that survive this life-threatening condition. If the trial fails to demonstrate effectiveness of prehospital sepsis treatments, it will ensure that resources are not needlessly invested in large-scale implementations of paramedic sepsis protocols, as has been done in several other jurisdictions. A lack of benefit would also cast doubt on the observational data suggesting that early antibiotics are important, and suggest a more restrained approach to empiric antibiotic therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This is a 2x2 factorial RCT, with simultaneous randomization of individual patients into 2 randomized controlled trials. The first RCT compares administration of 1g of intramuscular ceftriaxone versus placebo. In this RCT, participants, care providers, investigators, and outcome assessors will all be masked to the treatment allocation. The second RCT compares a liberal fluid resuscitation (up to 2litres of intravenous 0.9% saline) versus conventional resuscitation (administration of intravenous 0.9% saline, started only when systolic blood pressure is <90mmHg and only continued until systolic blood pressure is >= 100mmHg). In this RCT, only participants and outcome assessors will be masked.
| Arm | Type | Receives |
|---|---|---|
| Comparison 1: Prehospital Ceftriaxone | Active comparator | Drug: Comparison 1: Prehospital Ceftriaxone1g of Ceftriaxone will be administered by immediate intramuscular (IM) injection. The drug is provided in a sterile and completely covered vial as a white, odourless powder |
| Comparison 1: Placebo | Placebo comparator | Drug: Comparison 1: PlaceboThe placebo is provided in a sterile and completely covered vial. |
| Comparison 2: Liberal fluids | Experimental | Drug: Comparison 2: Liberal fluidsParamedics will administer up to 2 litres of intravenous 0.9% saline solution to all participants in this arm regardless of blood pressure, reassessing for signs of volume overload after each 250ml. |
| Comparison 2: Conservative fluids | Active comparator | Drug: Comparison 2: Conservative fluidsParamedics will administer 0.9% saline solution to participants who have systolic blood pressure <90mmHg, and will only continue the infusion until the systolic blood pressure is >=100mmHg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with Sepsis, defined as (all 3 must be present): i) Paramedic suspects possible infection: e.g. suspected pneumonia, urinary tract infection, skin infection, bone and joint infection, intra-abdominal infection, meningitis ii) Presence of fever: Temperature ≥ 38.0°C measured by paramedic or history of fever during previous 24 hours iii) Presence of hypotension: Systolic blood pressure < 100mmHg
- Age ≥ 18 years
Key exclusion criteria (12 listed)
- Post cardiac arrest
- Suspected ST-segment elevation myocardial infarction (STEMI)
- Suspected acute cerebrovascular accident (CVA)
- Acute severe trauma
- Obvious severe non-traumatic bleeding
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 |
|---|---|---|
| Comparison 1: Prehospital CeftriaxoneAlso: CeftriaxoneParamedics will administer 1g of intramuscular ceftriaxone. | Drug | Comparison 1: Prehospital Ceftriaxone |
| Comparison 1: PlaceboAlso: 0.9% saline for injectionParamedics will administer an identical volume of reconstituted intramuscular placebo. | Drug | Comparison 1: Placebo |
| Comparison 2: Liberal fluidsAlso: intravenous saline (0.9%) for injectionParamedics will administer up to 2 litres of intravenous saline (0.9%) to all patients regardless of systolic blood pressure, and reassessing this infusion after each 250ml are infused. | Drug | Comparison 2: Liberal fluids |
| Comparison 2: Conservative fluidsAlso: intravenous saline (0.9%) for injectionParamedics will administer intravenous saline (0.9%) according to the Medical Directive, which allows for infusion of fluids if systolic blood pressure is <90mmHg and continued until systolic blood pressure is >=100mmHg. | Drug | Comparison 2: Conservative fluids |
Primary outcome
Primary outcome: mortality prior to hospital discharge to day 90.
Time frame: 90 days
Dichotomous outcome reported as percentage
16 secondary outcomes
Mortality at 90 days after enrollment
Time frame: 90 days after enrollment
Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis
Time frame: 24 hours
Organ dysfunction during hospitalization (mechanical ventilation)
Time frame: until hospital discharge, measured up to maximum of day 90
duration of hospital admission (if any)
Time frame: until hospital discharge, measured up to maximum of day 90
duration of first ICU admission (if any)
Time frame: until ICU discharge, measured up to maximum of day 90
Proportion of patients with positive blood cultures obtained in hospital
Time frame: 24 hours
Microbiology results (if any)
Time frame: 24 hours
Proportion of patients receiving antibiotics within first 24 hours of hospitalization
Time frame: 24 hours
Frequency distribution and mean time to first dose of antibiotics (if any) within first 24 hours of hospitalization
Time frame: 24 hours
Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization
Time frame: 24 hours
Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)
Time frame: 24 hours
Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray
Time frame: during transport and on initial chest x-ray (if completed)
Proportion of patients with blood, urine, sputum cultures that grow organisms resistant to ceftriaxone
Time frame: 24 hours
Proportion of patients diagnosed with sepsis or infection by emergency department physician
Time frame: during admission
Proportion of hospitalized patients who grow any antibiotic-resistant organism (methicilin resistant S. aureus, Clostridium difficile, extended beta-lactamase resistant organisms)
Time frame: during admission
Proportion of patients with anaphylaxis or suspected allergic reactions to study medication
Time frame: during admission
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 20 Apr 2026.
- Derived from this study: PubMed 40436458Scales DC, Rogowsky A, Burry L, Christenson J, Daneman N, Drennan IR, Hillier M, Jenneson S, Klein G, Mazzulli T, Moran P, Morris AM, Morrison LJ, Pinto R, Rubenfeld GD, Seymour CW, Stenstrom R, Verbeek PR, Cheskes S. Prehospital antibiotics and intravenous fluids for patients with sepsis: protocol for a 2x2 factorial randomised controlled trial. BMJ Open. 2025 May 27;15(5):e104257. doi: 10.1136/bmjopen-2025-104257.
- 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.
Damon Scales, MD PhD FRCPC principal investigator
Sunnybrook Health Sciences Centre
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Comparison 1: Prehospital Ceftriaxone, Comparison 2: Liberal fluids and Comparison 2: Conservative fluids in people with Severe Sepsis or Septic Shock, run by Dr. Damon Scales 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 2 inclusion and 12 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 20 Apr 2026. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Primary outcome: mortality prior to hospital discharge to day 90. (time frame: 90 days). 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 NCT03068741, 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 20 Apr 2026.