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| Name | Class |
|---|---|
| BioMérieux | INDUSTRY |
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Children presenting for emergency department (ED) care with bloody diarrhea (i.e. hematochezia) represent a diagnostic challenge. Infectious enteric pathogens - Salmonella, Shigella and Shiga toxin-producing Escherichia coli (STEC) - are at the top of the differential diagnosis list. STEC is of greatest concern because ~15% of infected children develop the Hemolytic Uremic Syndrome (HUS). Our team has demonstrated that antibiotic administration to STEC-infected children increases the risk of developing HUS while dehydration is associated with mortality. Rapidly identifying children with STEC infection can reduce unnecessary resource use in uninfected children while providing them to those with confirmed STEC infection. The study team will conduct a prospective ED-based study that will randomly allocate 60 children to either standard care as dictated by the treating physician or to the use of a 22-pathogen, nucleic acid based, 1-hour run time diagnostic test. The study team will evaluate the impact of testing on clinical resource use, clinical outcomes, costs and patient satisfaction.
Background:
The rapid identification of STEC-infected children will enable the provision of appropriate and timely care to such children. The rapid identification of other enteric pathogens (bacteria, virus, parasite) will enable the provision of targeted therapies as appropriate and the withholding of avoidable interventions. It will also provide information for clinicians to consider alternate, non-infectious etiologies as appropriate. The study team hypothesize that the BioFire FilmArray can be used selectively in children with hematochezia to identify children with STEC infection and therefore will expeditiously identify children in need of therapeutic interventions and those for whom blood testing, intravenous fluids, and follow-up visits are unnecessary. Knowledge of the etiology early in the course of disease will enhance the provision of a patient-level precision medicine approach to what is otherwise an ill-defined symptom.
Study Design:
The study team will prospectively identify children who present with hematochezia. Potentially eligible subjects will be identified by our Pediatric Emergency Medicine Research Associate Program (PEMRAP) and the Pediatric Emergency Research Team (PERT) nurses (ED coverage 14 hours per day). Eligible children will have ≥3 episodes of diarrhea within the preceding 24 hours and will have had blood identified in the stool (by physician, nurse or parent ). Eligible subjects will be approached by a PERT team member to obtain consent (and assent when appropriate). Once consent has been obtained, study participants will be randomized by a REDCap randomization tool to ensure allocation concealment (i.e. research team, ED physicians will be unaware until after enrolled into the study and randomized).
Children randomized to the standard of care arm will have demographic and clinical information collected and the treating physician will be informed to proceed as per their usual practice and treatment patterns. If stool is unavailable a rectal swab will be collected and sent to Calgary Laboratory Services (CLS) for routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care. Home stool collection will be performed for those unable to provide a sample at enrolment and will be achieved by providing families with collection kits. Sample specimens may be stored at CLS as per routine procedures for standard clinical care. Following the completion of the visit, data regarding all testing, procedures, and medications administered will be collected. The family will be contacted 14 days later to collect outcome information (clinical and health resource use) and satisfaction. The medical records and select administrative databases may be reviewed to ascertain and confirm outcome data on Day 28.
Children randomized to the BioFire FilmArray arm will have the same data collected, but stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Sample specimens may be stored at CLS as per routine procedures for standard clinical care. The result of the BioFire test will be printed and brought to the ED where it will be provided to the ED physician for immediate review and management as appropriate. The result will be included in the ED chart for documentation purposes. Education regarding the interpretation of BioFire FilmArray results will have been performed in advance to all faculty members and a research team member will be available to answer any questions should they arise. We have worked with leaders at CLS including Drs. Gregson, Berenger and Vanderkooi who believe we should be able to receive a result within 2-3 hours of receipt of the specimen at CLS. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. Following the completion of the visit, data regarding all testing, procedures, and medications administered will be collected. The family will be contacted 14 days later to collect outcome information (clinical and health resource use) and satisfaction. The medical records and select administrative databases may be reviewed to ascertain and confirm outcome data on Day 28.
For those who decline consent, the study team will request consent to access select administrative data, Netcare and/or access to the child's medical records related to the illness to document interventions and outcomes in order to be able to assess bias by comparing participating and non-participating children in this study.
Objectives:
Primary Objective
1. To determine if use of the BioFire FilmArray in children with hematochezia results in a reduction in resource utilization. Primary outcome - any blood tests (dichotomous with sub-analysis by specific blood tests); secondary - intravenous fluid administration, ED encounters.
Secondary Objectives
Significance:
The study team intend to determine new knowledge:
Potential child health improvements:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care | Active Comparator | For children randomized to the standard of care arm, the treating physician will be informed to proceed as per their usual practice and treatment patterns. If stool is unavailable a rectal swab will be collected and sent to Calgary Laboratory Services (CLS) for routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care. Home stool collection will be performed for those unable to provide a sample at enrolment and will be achieved by providing families with collection kits. |
|
| BioFire Gastrointestinal Panel FilmArray | Experimental | For children randomized to the BioFire FilmArray arm, stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BioFire Gastrointestinal Panel FilmArray® | Device | The BioFire Gastrointestinal Panel FilmArray® is a multiplexed nucleic acid (NA) based device that simultaneously identifies 22 enteric pathogens. It specifically tests for the presence of Shiga toxin and for O157. It requires 2 minutes of hands-on-time, returns results in ~2-3 hour, and is Health Canada and Food and Drug Administration approved. The device, which has been validated, hopefully will enable the early identification of infected children and initiation (or withholding) of interventions directed by previously unavailable clinical data. It will enable us to bring a precision medicine approach into ED care. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood Test Performance | Any blood testing performed within 72 hours of randomization. | Day 28 of the study after baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Intravenous Fluid Administration | Children administered IV fluids identified by chart review. | Day 28 of the study after baseline |
| Total Physician Visits (ED and Non-ED) | Children visiting additional health-care practitioners identified by chart review. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Freedman, MDCM, MSc | University of Calgary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15930195 | Background | Ake JA, Jelacic S, Ciol MA, Watkins SL, Murray KF, Christie DL, Klein EJ, Tarr PI. Relative nephroprotection during Escherichia coli O157:H7 infections: association with intravenous volume expansion. Pediatrics. 2005 Jun;115(6):e673-80. doi: 10.1542/peds.2004-2236. | |
| 21784993 | Background | Hickey CA, Beattie TJ, Cowieson J, Miyashita Y, Strife CF, Frem JC, Peterson JM, Butani L, Jones DP, Havens PL, Patel HP, Wong CS, Andreoli SP, Rothbaum RJ, Beck AM, Tarr PI. Early volume expansion during diarrhea and relative nephroprotection during subsequent hemolytic uremic syndrome. Arch Pediatr Adolesc Med. 2011 Oct;165(10):884-9. doi: 10.1001/archpediatrics.2011.152. Epub 2011 Jul 22. |
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Recruitment occurred between June 15, 2018 through May 7, 2022 in the emergency department of the Alberta Children's Hospital located in Calgary, Alberta, Canada.
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| ID | Title | Description |
|---|---|---|
| FG000 | Standard of Care | For children randomized to the standard of care arm, the treating physician will be informed to proceed as per their usual practice and treatment patterns. If stool is unavailable a rectal swab will be collected and sent to Calgary Laboratory Services (CLS) for routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care. Home stool collection will be performed for those unable to provide a sample at enrolment and will be achieved by providing families with collection kits. Standard of Care: Standard practices for children with hematochezia upon the discretion of the treating physician. If investigations are ordered, results have a turn-around time up to 72 hours. |
| FG001 | BioFire Gastrointestinal Panel FilmArray | For children randomized to the BioFire FilmArray arm, stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. BioFire Gastrointestinal Panel FilmArray®: The BioFire Gastrointestinal Panel FilmArray® is a multiplexed nucleic acid (NA) based device that simultaneously identifies 22 enteric pathogens. It specifically tests for the presence of Shiga toxin and for O157. It requires 2 minutes of hands-on-time, returns results in ~2-3 hour, and is Health Canada and Food and Drug Administration approved. The device, which has been validated, hopefully will enable the early identification of infected children and initiation (or withholding) of interventions directed by previously unavailable clinical data. It will enable us to bring a precision medicine approach into ED care. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Standard of Care | For children randomized to the standard of care arm, the treating physician will be informed to proceed as per their usual practice and treatment patterns. If stool is unavailable a rectal swab will be collected and sent to Calgary Laboratory Services (CLS) for routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care. Home stool collection will be performed for those unable to provide a sample at enrolment and will be achieved by providing families with collection kits. Standard of Care: Standard practices for children with hematochezia upon the discretion of the treating physician. If investigations are ordered, results have a turn-around time up to 72 hours. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Blood Test Performance | Any blood testing performed within 72 hours of randomization. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
Adverse events were monitored for while in the emergency department, which was a median of 4.6 hours (IQR: 3.4-5.6).
Adverse event definition did not differ from cliniclatrials.gov definition
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Standard of Care | For children randomized to the standard of care arm, the treating physician will be informed to proceed as per their usual practice and treatment patterns. If stool is unavailable a rectal swab will be collected and sent to Calgary Laboratory Services (CLS) for routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care. Home stool collection will be performed for those unable to provide a sample at enrolment and will be achieved by providing families with collection kits. Standard of Care: Standard practices for children with hematochezia upon the discretion of the treating physician. If investigations are ordered, results have a turn-around time up to 72 hours. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Stephen Freedman | University of Calgary | 403-955-7740 | stephen.freedman@ahs.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 16, 2018 | May 20, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D006471 | Gastrointestinal Hemorrhage |
| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
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Data extractors and Investigators will be unaware of allocation assignment.
|
| Standard of Care | Other | Standard practices for children with hematochezia upon the discretion of the treating physician. If investigations are ordered, results have a turn-around time up to 72 hours. |
|
| Day 28 of the study after baseline |
| ED Length of Stay | ED length of stay during enrollment visit determined by chart review. | Day 28 of the study after baseline |
| Antibiotic Use | Antibiotic use identified by chart review. | Day 28 of the study after baseline |
| Hospital and Intensive Care Unit Admission | Hospitalization identified by chart review. | Day 28 of the study after baseline |
| Diagnostic Imaging Performed | Diagnostic imaging performed identified by chart review. | Day 28 of the study after baseline |
| Hemolytic-Uremic Syndrome (HUS) | Children with HUS identified by chart review. | Day 28 of the study after baseline |
| Acute Kidney Injury | Based on chart review in accordance with KDIGO guidelines. | Day 28 of the study after baseline |
| Need for Renal Replacement Therapy | Renal replacement therapy identified by chart review. | Day 28 of the study after baseline |
| Caregiver and Patient Satisfaction | Satisfaction of care received during ED visit answered in Day 14 follow-up form on a Likert scale. Caregivers were asked the following question: "Using any number from 0 to 10, where 0 is the worst care possible and 10 is the best care possible, what number would you use to rate your child's care during the emergency department visit (Day 0 - Enrollment visit)?" the scale does not have a name or specific construct beyond as detailed in the script that was used to ask the question. The range is from 0 (minimum) to 10 (maximum). There are no sub-scales. Higher values represent greater satisfaction. | Day 14 of the study after baseline |
| 16941358 | Background | Klein EJ, Boster DR, Stapp JR, Wells JG, Qin X, Clausen CR, Swerdlow DL, Braden CR, Tarr PI. Diarrhea etiology in a Children's Hospital Emergency Department: a prospective cohort study. Clin Infect Dis. 2006 Oct 1;43(7):807-13. doi: 10.1086/507335. Epub 2006 Aug 22. |
| 12183710 | Background | Klein EJ, Stapp JR, Clausen CR, Boster DR, Wells JG, Qin X, Swerdlow DL, Tarr PI. Shiga toxin-producing Escherichia coli in children with diarrhea: a prospective point-of-care study. J Pediatr. 2002 Aug;141(2):172-7. doi: 10.1067/mpd.2002.125908. |
| 18444854 | Background | Werber D, Mason BW, Evans MR, Salmon RL. Preventing household transmission of Shiga toxin-producing Escherichia coli O157 infection: promptly separating siblings might be the key. Clin Infect Dis. 2008 Apr 15;46(8):1189-96. doi: 10.1086/587670. |
| BG001 | BioFire Gastrointestinal Panel FilmArray | For children randomized to the BioFire FilmArray arm, stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. BioFire Gastrointestinal Panel FilmArray®: The BioFire Gastrointestinal Panel FilmArray® is a multiplexed nucleic acid (NA) based device that simultaneously identifies 22 enteric pathogens. It specifically tests for the presence of Shiga toxin and for O157. It requires 2 minutes of hands-on-time, returns results in ~2-3 hour, and is Health Canada and Food and Drug Administration approved. The device, which has been validated, hopefully will enable the early identification of infected children and initiation (or withholding) of interventions directed by previously unavailable clinical data. It will enable us to bring a precision medicine approach into ED care. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Inter-Quartile Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | BioFire Gastrointestinal Panel FilmArray | For children randomized to the BioFire FilmArray arm, stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. BioFire Gastrointestinal Panel FilmArray®: The BioFire Gastrointestinal Panel FilmArray® is a multiplexed nucleic acid (NA) based device that simultaneously identifies 22 enteric pathogens. It specifically tests for the presence of Shiga toxin and for O157. It requires 2 minutes of hands-on-time, returns results in ~2-3 hour, and is Health Canada and Food and Drug Administration approved. The device, which has been validated, hopefully will enable the early identification of infected children and initiation (or withholding) of interventions directed by previously unavailable clinical data. It will enable us to bring a precision medicine approach into ED care. |
|
|
| Secondary | Intravenous Fluid Administration | Children administered IV fluids identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Total Physician Visits (ED and Non-ED) | Children visiting additional health-care practitioners identified by chart review. | Posted | Median | Inter-Quartile Range | physician visits | Day 28 of the study after baseline |
|
|
|
| Secondary | ED Length of Stay | ED length of stay during enrollment visit determined by chart review. | Posted | Median | Inter-Quartile Range | hours | Day 28 of the study after baseline |
|
|
|
| Secondary | Antibiotic Use | Antibiotic use identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Hospital and Intensive Care Unit Admission | Hospitalization identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Diagnostic Imaging Performed | Diagnostic imaging performed identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Hemolytic-Uremic Syndrome (HUS) | Children with HUS identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Acute Kidney Injury | Based on chart review in accordance with KDIGO guidelines. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Need for Renal Replacement Therapy | Renal replacement therapy identified by chart review. | Posted | Count of Participants | Participants | Day 28 of the study after baseline |
|
|
|
| Secondary | Caregiver and Patient Satisfaction | Satisfaction of care received during ED visit answered in Day 14 follow-up form on a Likert scale. Caregivers were asked the following question: "Using any number from 0 to 10, where 0 is the worst care possible and 10 is the best care possible, what number would you use to rate your child's care during the emergency department visit (Day 0 - Enrollment visit)?" the scale does not have a name or specific construct beyond as detailed in the script that was used to ask the question. The range is from 0 (minimum) to 10 (maximum). There are no sub-scales. Higher values represent greater satisfaction. | Posted | Median | Inter-Quartile Range | units on a scale | Day 14 of the study after baseline |
|
|
|
| 0 |
| 29 |
| 0 |
| 29 |
| 0 |
| 29 |
| EG001 | BioFire Gastrointestinal Panel FilmArray | For children randomized to the BioFire FilmArray arm, stool, if available, will be sent STAT to Calgary Laboratory Services (CLS) for the performance of the BioFire FilmArray test and routine culture. If stool is unavailable, a rectal swab will be performed and sent to CLS for the performance of the BioFire FilmArray test and routine culture. A routine stool specimen for back-up culture will still be requested as per standard of care once it is available. Treatment decisions will be at the sole discretion of the ED treating physician who receives the result. BioFire Gastrointestinal Panel FilmArray®: The BioFire Gastrointestinal Panel FilmArray® is a multiplexed nucleic acid (NA) based device that simultaneously identifies 22 enteric pathogens. It specifically tests for the presence of Shiga toxin and for O157. It requires 2 minutes of hands-on-time, returns results in ~2-3 hour, and is Health Canada and Food and Drug Administration approved. The device, which has been validated, hopefully will enable the early identification of infected children and initiation (or withholding) of interventions directed by previously unavailable clinical data. It will enable us to bring a precision medicine approach into ED care. | 0 | 31 | 0 | 31 | 0 | 31 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |