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

Primary Purpose

Severe Sepsis or Septic Shock

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Comparison 1: Prehospital Ceftriaxone
Comparison 1: Placebo
Comparison 2: Liberal fluids
Comparison 2: Conservative fluids
Sponsored by
Dr. Damon Scales
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Severe Sepsis or Septic Shock

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Halton Region Paramedic ServicesRecruiting
  • Peel Region Paramedic ServicesRecruiting
  • Toronto Paramedic ServicesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Placebo Comparator

Experimental

Active Comparator

Arm Label

Comparison 1: Prehospital Ceftriaxone

Comparison 1: Placebo

Comparison 2: Liberal fluids

Comparison 2: Conservative fluids

Arm Description

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

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

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.

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.

Outcomes

Primary Outcome Measures

Primary outcome: mortality prior to hospital discharge to day 90.
Dichotomous outcome reported as percentage

Secondary Outcome Measures

Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis
Dichotomous outcome reported as percentage
Organ dysfunction during hospitalization (mechanical ventilation)
Dichotomous outcome reported as percentage
duration of hospital admission (if any)
Measured in days from time of randomization
duration of first ICU admission (if any)
Measured in days from time of randomization
Proportion of patients with positive blood cultures obtained in hospital
Dichotomous outcome reported as percentage
Microbiology results (if any)
Descriptive outcome, reported as frequency distribution of positive culture results
Proportion of patients receiving antibiotics within first 24 hours of hospitalization
Dichotomous outcome reported as percentage
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
Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization
measured in milliliters
Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)
measured in milliliters
Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray
Dichotomous outcome reported as percentage
Proportion of patients with blood, urine, sputum cultures that grow organisms resistant to ceftriaxone
Dichotomous outcome reported as percentage
Proportion of patients diagnosed with sepsis or infection by emergency department physician
Dichotomous outcome reported as percentage
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
Proportion of patients with anaphylaxis or suspected allergic reactions to study medication
Dichotomous outcome reported as percentage

Full Information

First Posted
February 6, 2017
Last Updated
February 22, 2023
Sponsor
Dr. Damon Scales
Collaborators
Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03068741
Brief Title
Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
Acronym
PITSTOP
Official Title
Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2020 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Damon Scales
Collaborators
Canadian Institutes of Health Research (CIHR), Sunnybrook Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Sepsis or Septic Shock

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The study drug and placebo are prepared in identical masked containers.
Allocation
Randomized
Enrollment
2040 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Comparison 1: Prehospital Ceftriaxone
Arm Type
Active Comparator
Arm Description
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
Arm Title
Comparison 1: Placebo
Arm Type
Placebo Comparator
Arm Description
The placebo is provided in a sterile and completely covered vial.
Arm Title
Comparison 2: Liberal fluids
Arm Type
Experimental
Arm Description
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.
Arm Title
Comparison 2: Conservative fluids
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Comparison 1: Prehospital Ceftriaxone
Other Intervention Name(s)
Ceftriaxone
Intervention Description
Paramedics will administer 1g of intramuscular ceftriaxone.
Intervention Type
Drug
Intervention Name(s)
Comparison 1: Placebo
Other Intervention Name(s)
0.9% saline for injection
Intervention Description
Paramedics will administer an identical volume of reconstituted intramuscular placebo.
Intervention Type
Drug
Intervention Name(s)
Comparison 2: Liberal fluids
Other Intervention Name(s)
intravenous saline (0.9%) for injection
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Comparison 2: Conservative fluids
Other Intervention Name(s)
intravenous saline (0.9%) for injection
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary outcome: mortality prior to hospital discharge to day 90.
Description
Dichotomous outcome reported as percentage
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis
Description
Dichotomous outcome reported as percentage
Time Frame
24 hours
Title
Organ dysfunction during hospitalization (mechanical ventilation)
Description
Dichotomous outcome reported as percentage
Time Frame
until hospital discharge, measured up to maximum of day 90
Title
duration of hospital admission (if any)
Description
Measured in days from time of randomization
Time Frame
until hospital discharge, measured up to maximum of day 90
Title
duration of first ICU admission (if any)
Description
Measured in days from time of randomization
Time Frame
until ICU discharge, measured up to maximum of day 90
Title
Proportion of patients with positive blood cultures obtained in hospital
Description
Dichotomous outcome reported as percentage
Time Frame
24 hours
Title
Microbiology results (if any)
Description
Descriptive outcome, reported as frequency distribution of positive culture results
Time Frame
24 hours
Title
Proportion of patients receiving antibiotics within first 24 hours of hospitalization
Description
Dichotomous outcome reported as percentage
Time Frame
24 hours
Title
Frequency distribution and mean time to first dose of antibiotics (if any) within first 24 hours of hospitalization
Description
Measured in hours from time of randomization
Time Frame
24 hours
Title
Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization
Description
measured in milliliters
Time Frame
24 hours
Title
Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)
Description
measured in milliliters
Time Frame
24 hours
Title
Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray
Description
Dichotomous outcome reported as percentage
Time Frame
during transport and on initial chest x-ray (if completed)
Title
Proportion of patients with blood, urine, sputum cultures that grow organisms resistant to ceftriaxone
Description
Dichotomous outcome reported as percentage
Time Frame
24 hours
Title
Proportion of patients diagnosed with sepsis or infection by emergency department physician
Description
Dichotomous outcome reported as percentage
Time Frame
during admission
Title
Proportion of hospitalized patients who grow any antibiotic-resistant organism (methicilin resistant S. aureus, Clostridium difficile, extended beta-lactamase resistant organisms)
Description
Dichotomous outcome reported as percentage
Time Frame
during admission
Title
Proportion of patients with anaphylaxis or suspected allergic reactions to study medication
Description
Dichotomous outcome reported as percentage
Time Frame
during admission

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Damon Scales, MD PhD FRCPC
Phone
416-480-5291
Email
damon.scales@sunnybrook.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Project Manager
Phone
416-480-5654
Email
pitstop@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Damon Scales, MD PhD FRCPC
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Halton Region Paramedic Services
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chief Greg Sage
Facility Name
Peel Region Paramedic Services
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chief Peter Dundas
Facility Name
Toronto Paramedic Services
City
Toronto
State/Province
Ontario
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chief Bikram Chawla

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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