Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)

NCT03068741 | Completed Phase 4 DMC

• 1 other identifier: The PITSTOP RCT
• Study Type: interventional
• Target: 2,061
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Severe Sepsis or Septic Shock

Outcome Measures

Primary Outcomes (1)

• Primary outcome: mortality prior to hospital discharge to day 90.

  Dichotomous outcome reported as percentage

  90 days

Secondary Outcomes (16)

• Mortality at 90 days after enrollment

  90 days after enrollment

• Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis

  24 hours

• Organ dysfunction during hospitalization (mechanical ventilation)

  until hospital discharge, measured up to maximum of day 90

• duration of hospital admission (if any)

  until hospital discharge, measured up to maximum of day 90

• duration of first ICU admission (if any)

  until ICU discharge, measured up to maximum of day 90

Study Arms (4)

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

Drug: Comparison 1: Prehospital Ceftriaxone

Comparison 1: Placebo

PLACEBO COMPARATOR

The placebo is provided in a sterile and completely covered vial.

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.

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.

Drug: Comparison 2: Conservative fluids

Interventions

Comparison 1: Prehospital Ceftriaxone DRUG

Paramedics will administer 1g of intramuscular ceftriaxone.

Also known as: Ceftriaxone

Comparison 1: Prehospital Ceftriaxone

Comparison 1: Placebo DRUG

Paramedics will administer an identical volume of reconstituted intramuscular placebo.

Also known as: 0.9% saline for injection

Comparison 1: Placebo

Comparison 2: Liberal fluids DRUG

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.

Also known as: intravenous saline (0.9%) for injection

Comparison 2: Liberal fluids

Comparison 2: Conservative fluids DRUG

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.

Also known as: intravenous saline (0.9%) for injection

Comparison 2: Conservative fluids

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Dr. Damon Scales: lead
• Sunnybrook Research Institute: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (4)

Halton Region Paramedic Services

Toronto, Ontario, Canada

Location

Peel Region Paramedic Services

Toronto, Ontario, Canada

Location

Toronto Paramedic Services

Toronto, Ontario, Canada

Location

York Region Paramedic Services

Toronto, Ontario, Canada

Location

Related Publications (1)

• 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.

  PMID: 40436458 DERIVED

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Ceftriaxone; Sodium Chloride; Injections

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Damon Scales, MD PhD FRCPC

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study drug and placebo are prepared in identical masked containers.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, FRCPC

Model Details: 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.

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: March 3, 2017
• Study Start: March 23, 2020
• Primary Completion: November 17, 2025
• Study Completion: November 17, 2025
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (4)