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

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.

Study Overview

• Status: Recruiting
• Conditions: Severe Sepsis or Septic Shock
• Intervention / Treatment: Drug: Comparison 1: Prehospital Ceftriaxone; Drug: Comparison 1: Placebo; Drug: Comparison 2: Liberal fluids; Drug: Comparison 2: Conservative fluids

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 Type: Interventional
• Enrollment (Estimated): 2040
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Damon Scales, MD PhD FRCPC; Phone Number: 416-480-5291; Email: damon.scales@sunnybrook.ca
• Study Contact Backup: Name: Project Manager; Phone Number: 416-480-5654; Email: pitstop@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Recruiting
      • Halton Region Paramedic Services
      • Contact: Chief Greg Sage
    • Toronto, Ontario, Canada
      • Recruiting
      • Peel Region Paramedic Services
      • Contact: Chief Peter Dundas
    • Toronto, Ontario, Canada
      • Recruiting
      • Toronto Paramedic Services
      • Contact: Chief Bikram Chawla
    • Toronto, Ontario, Canada
      • Recruiting
      • York Region Paramedic Services
      • Contact: Chief Chris Spearen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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
2. Age ≥ 18 years

Exclusion Criteria:

1. Post cardiac arrest
2. Suspected ST-segment elevation myocardial infarction (STEMI)
3. Suspected acute cerebrovascular accident (CVA)
4. Acute severe trauma
5. Obvious severe non-traumatic bleeding
6. Signs of fluid overload
7. Suspected acute congestive heart failure (CHF)
8. Known Clostridium difficile infection within the last 6 weeks
9. Known pregnancy or breastfeeding
10. Known allergy or sensitivity to penicillin or cephalosporin
11. Receiving oral or subcutaneous anticoagulants or low molecular weight heparin
12. Paramedic is unable to identify patient by first and last name and/or health card number

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Comparison 1: Prehospital Ceftriaxone; 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; Paramedics will administer 1g of intramuscular ceftriaxone.; Other Names: Ceftriaxone
Placebo Comparator: Comparison 1: Placebo; The placebo is provided in a sterile and completely covered vial.	Drug: Comparison 1: Placebo; Paramedics will administer an identical volume of reconstituted intramuscular placebo.; Other Names: 0.9% saline for injection
Experimental: Comparison 2: Liberal fluids; 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; 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.; Other Names: intravenous saline (0.9%) for injection
Active Comparator: Comparison 2: Conservative fluids; 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; 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.; Other Names: intravenous saline (0.9%) for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary outcome: mortality prior to hospital discharge to day 90.	Dichotomous outcome reported as percentage	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis	Dichotomous outcome reported as percentage	24 hours
Organ dysfunction during hospitalization (mechanical ventilation)	Dichotomous outcome reported as percentage	until hospital discharge, measured up to maximum of day 90
duration of hospital admission (if any)	Measured in days from time of randomization	until hospital discharge, measured up to maximum of day 90
duration of first ICU admission (if any)	Measured in days from time of randomization	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	24 hours
Microbiology results (if any)	Descriptive outcome, reported as frequency distribution of positive culture results	24 hours
Proportion of patients receiving antibiotics within first 24 hours of hospitalization	Dichotomous outcome reported as percentage	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	24 hours
Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization	measured in milliliters	24 hours
Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)	measured in milliliters	24 hours
Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray	Dichotomous outcome reported as percentage	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	24 hours
Proportion of patients diagnosed with sepsis or infection by emergency department physician	Dichotomous outcome reported as percentage	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	during admission
Proportion of patients with anaphylaxis or suspected allergic reactions to study medication	Dichotomous outcome reported as percentage	during admission

Collaborators and Investigators

• Sponsor: Dr. Damon Scales
• Collaborators: Canadian Institutes of Health Research (CIHR); Sunnybrook Research Institute
• Investigators: Principal Investigator: Damon Scales, MD PhD FRCPC, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 6, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Anti-Infective Agents; Anti-Bacterial Agents; Third Generation Cephalosporins; Beta Lactam Antibiotics; Ceftriaxone
• Other Study ID Numbers: The PITSTOP RCT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No