Clinical trial NCT03068741: Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
Official title: Paramedic Initiated Treatment of Sepsis Targeting Out-of-hospital Patients (PITSTOP)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Severe Sepsis or Septic Shock
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Sunnybrook Research Institute
First posted: 2017-03-03
Enrollment: 2040
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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. Known to be 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

Primary outcomes:
measure: Primary outcome: mortality prior to hospital discharge to day 90.
timeFrame: 90 days
Secondary outcomes:
measure: Mortality at 90 days after enrollment
timeFrame: 90 days after enrollment
measure: Organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy (any), dialysis
timeFrame: 24 hours
measure: Organ dysfunction during hospitalization (mechanical ventilation)
timeFrame: until hospital discharge, measured up to maximum of day 90
measure: duration of hospital admission (if any)
timeFrame: until hospital discharge, measured up to maximum of day 90
measure: duration of first ICU admission (if any)
timeFrame: until ICU discharge, measured up to maximum of day 90
measure: Proportion of patients with positive blood cultures obtained in hospital
timeFrame: 24 hours
measure: Microbiology results (if any)
timeFrame: 24 hours
measure: Proportion of patients receiving antibiotics within first 24 hours of hospitalization
timeFrame: 24 hours
measure: Frequency distribution and mean time to first dose of antibiotics (if any) within first 24 hours of hospitalization
timeFrame: 24 hours
measure: Proportion of patients receiving IV fluids (>250mL) within first 24 hours of hospitalization
timeFrame: 24 hours
measure: Total amount of IV fluids administered during transport and first 24 hours of hospitalization (if any)
timeFrame: 24 hours
measure: Proportion of patients with pulmonary edema identified during transport to hospital and on initial chest x-ray
timeFrame: during transport and on initial chest x-ray (if completed)
measure: Proportion of patients with blood, urine, sputum cultures that grow organisms resistant to ceftriaxone
timeFrame: 24 hours
measure: Proportion of patients diagnosed with sepsis or infection by emergency department physician
timeFrame: during admission
measure: Proportion of hospitalized patients who grow any antibiotic-resistant organism (methicilin resistant S. aureus, Clostridium difficile, extended beta-lactamase resistant organisms)
timeFrame: during admission
measure: Proportion of patients with anaphylaxis or suspected allergic reactions to study medication
timeFrame: during admission
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Halton Region Paramedic Services
state: Ontario
city: Toronto
country: Canada
facility: Peel Region Paramedic Services
state: Ontario
city: Toronto
country: Canada
facility: Toronto Paramedic Services
state: Ontario
city: Toronto
country: Canada
facility: York Region Paramedic Services
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Damon Scales, MD PhD FRCPC
role: PRINCIPAL_INVESTIGATOR
References: