C-reactive Protein Information and Blood Cultures for Emergency Department Patients With Sepsis

A Multi-center Randomized Controlled Trial of C-reactive Protein Measurement on Ordering of Blood Cultures in Emergency Department Patients With Sepsis

Patients with sepsis (2 or more systemic inflammatory response syndrome criteria and suspected infection) assessed in the emergency department have blood cultures obtained to identify potential blood stream infections (BSI). Blood cultures are expensive, sometimes inaccurate, and only positive about 10% of the time in the emergency department.

This study evaluates the effect of physician knowledge of C-reactive protein (CRP) levels on ordering rates of blood cultures in emergency department patients with sepsis. All patients with sepsis will have CRP levels measured using a point-of-care device, prior to blood tests being ordered. Half of participants will have their CRP level available to the emergency physician and half will not. Blood culture ordering rate and safety outcomes will be compared between these two groups.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Bacteremia; Infection
• Intervention / Treatment: Other: CRP

Detailed Description

Sepsis, which is defined as the presence of a systemic inflammatory response syndrome (SIRS) in conjunction with a suspected or proven infection, is a significant cause of morbidity and mortality. It is an extremely common presentation in emergency departments. Most sepsis protocols and guidelines call for blood cultures to be obtained in patients with sepsis, in order to identify blood stream infections (BSI) which are usually caused by bacteria in the blood.

Blood cultures obtained in the emergency department are costly, subject to false positive results, and only positive about 10% of the time. Also, they rarely change patient management.

C-reactive protein (CRP) is an inflammatory marker that rises rapidly in the presence of bacterial infections. Because CRP rises as much as 100 times normal levels in the presence of bacterial infections, we have used it successfully to identify patients with sepsis who do not require a blood blood culture, we believe that physicians knowledge of CRP levels can help to guide their decision to order blood cultures.Patients with sepsis (2 or more SIRS criteria and presumed infection) will have their CRP levels measured using a point of care device (Alere Afinion AS100 Analyzer) prior to blood tests being ordered. Patients will be randomized to either have their CRP value shown to the attending physician or not. Rates of blood culture ordering and safety outcomes will then be compared between the two groups.

• Study Type: Interventional
• Enrollment (Anticipated): 208
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V1S1Y1
      • St Paul's Hospital
    • Vancouver, British Columbia, Canada, V5T 3N4
      • Mount St Joseph's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Emergency department patients with sepsis: Known or presumed infection and 2 or more SIRS criteria: heart rate > 90/minute; respiratory rate > 20/minute; Oral temperature ≥ 38◦ C or < 36◦ C; white blood cell count > 12,000 or < 4,000.
• Able to read and understand consent form in English
• Age 19 years or greater

Exclusion Criteria:

• Patients presenting with septic shock (systolic blood pressure < 90 mmHG)
• Patients at risk for endocarditis (previous episodes of endocarditis, injection drug use)
• Imuno-compromised patients: HIV positive and not on anti-retrovirals; active chemotherapy ; known immune disorder; on immune system modulating drugs, including corticosteroids.
• indwelling venous catheter (dialysis line, Hickman catheter)
• hospitalization in previous 2 weeks
• Surgical procedure in previous 2 weeks

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CRP value; The patients point of care CRP value is known by the treating physician	Other: CRP; Knowledge of CRP value
ACTIVE_COMPARATOR: CRP value unknown; The patients point of care CRP value is not known by the treating physician	Other: CRP; Knowledge of CRP value

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood culture obtained	Blood cultures ordered (Yes/No)	8 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28 day mortality	Patient died within 28 days	28 days
false positive blood culture	false positive blood culture (Y/N)	28 days
Antibiotic prescribing	number of antibiotic prescriptions provided	7 days
length of stay	Length of emergency department stay (days)	28 days
Admission to hospital	patient admitted to hospital (yes/No)	7 days

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Providence Health & Services
• Investigators: Principal Investigator: Robert Stenstrom, MD, PhD, Providence Health & Services

Publications and helpful links

General Publications

• Kyriazopoulou E, Poulakou G, Giamarellos-Bourboulis EJ. Biomarkers in sepsis: can they help improve patient outcome? Curr Opin Infect Dis. 2021 Apr 1;34(2):126-134. doi: 10.1097/QCO.0000000000000707.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 21, 2017
• Primary Completion (ACTUAL): September 15, 2020
• Study Completion (ANTICIPATED): May 15, 2021

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: October 18, 2018
• First Posted (ACTUAL): October 22, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 18, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: randomized controlled trial; C reactive protein; Blood culture
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Toxemia; Emergencies; Bacteremia
• Other Study ID Numbers: H15-03281

Drug and device information, study documents

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