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Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort (PDAID)

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ClinicalTrials.gov Identifier: NCT02910037
Recruitment Status : Completed
First Posted : September 21, 2016
Last Update Posted : April 13, 2018
Sponsor:
Collaborators:
California Initiative to Advance Precision Medicine
Sandler Foundation
Bowes Foundation
Charles and Helen Schwab Foundation
University of California, Davis
University of California, Los Angeles
Children's Hospital Los Angeles
Children's Hospital Colorado
St. Jude Children's Research Hospital
Children's Research Institute
University of California, Berkeley
DNAnexus, Inc.
Syapse, Inc.
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:
This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients. From June 2016 to June 2017, 200 patients will be enrolled from multiple hospitals in California and outside of California. Patients will be evaluated to determine the impact on the mNGS assay on diagnostic yield, hospital costs and clinical outcomes.

Condition or disease Intervention/treatment Phase
Encephalitis Meningitis Device: mNGS for pathogen detection Not Applicable

Detailed Description:
This study aims to use a clinically validated metagenomic next-generation sequencing (mNGS) assay to provide a demonstration of precision medicine for diagnosis of acute infectious disease in hospitalized patients, with the goal of directly impacting clinical care and improving patient mortality. This diagnostic test has been previously validated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, the University of California, San Francisco Clinical Microbiology Laboratory. From June 2016 to June 2017, investigators will prospectively enroll 200 patients from multiple hospitals in California (University of California, San Francisco; University of California, Los Angeles; University of California, Davis; Children's Hospital Los Angeles) and outside California (Children's National Medical Center, Children's Hospital Colorado, St. Jude Children's Research Hospital) for mNGS testing, and evaluate the impact on the assay on diagnostic yield, hospital costs and clinical outcomes.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 204 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Clinical Implementation of Metagenomic Next-Generation Sequencing for Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
Actual Study Start Date : June 1, 2016
Actual Primary Completion Date : July 31, 2017
Actual Study Completion Date : July 31, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: patients enrolled for mNGS testing
Patients with meningitis and/or encephalitis will be enrolled in this study in order to analyze the clinical utility of mNGS for pathogen detection. There is no control group for this study (Investigators will identify historical controls by retrospective chart review and clinical reimbursement documents).
Device: mNGS for pathogen detection
This assay is a laboratory-validated metagenomic test for comprehensive detection of viruses, bacteria, fungi, and parasites in clinical samples.
Other Names:
  • Sequence-Based Ultrarapid Pathogen Identification (SURPI)+
  • UCSF metagenomic next-generation sequencing testing




Primary Outcome Measures :
  1. Impact on clinical reasoning and management [ Time Frame: within 1 month of patient enrollment in study ]
    Investigators will evaluate impact of mNGS assay by clinician surveys and Clinical Microbial Sequencing Board (CMSB) feedback and discussion


Secondary Outcome Measures :
  1. Cost of care for patients hospitalized for encephalitis/meningitis [ Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study (ends June 2017) ]
    Two data sets will be used during the duration of this study. Claims data will be used to analyze 5 years of retrospective cost data on patients hospitalized with encephalitis and/or meningitis. This data set will be used to establish a reference for total cost of care, average length of stay and number of invasive procedures. Statistical models will be proposed to evaluate the cost-effectiveness based on time of intervention of the mNGS assay for pathogen detection (i.e. at presentation in emergency department, at time of repeat lumbar puncture, or based on hospital location - Emergency Department to Intensive Care Unit). Patients enrolled in this research study will also be consented to sharing billing data with the investigators. This will be evaluated and compared to the retrospective claims data.

  2. Clinical outcomes: time to diagnosis [ Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study (ends June 2017) ]
    Investigators will review medical records to determine time to definitive diagnosis for patients enrolled in the study.

  3. Clinical outcomes: length of stay [ Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study (ends June 2017) ]
    Investigators will review medical records to determine length of stay including discharge to rehab facilities.

  4. Clinical outcomes: treatments given and time to targeted therapy [ Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study (ends June 2017) ]
    Investigators will review medical records and discuss with treatment teams to determine therapies given and treatment strategy to measure time to targeted therapy.

  5. Clinical outcomes: number of diagnostic tests and invasive procedures [ Time Frame: from admission to 1 month post discharge for each patient during the enrollment period of study (ends June 2017) ]
    Investigators will review medical records and discuss with treatment teams to track the number of diagnostic tests send and invasive procedures performed before definitive diagnosis established for patients enrolled in study.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 110 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Exclusions:

  • Patients on a 5150 or 5250 psychiatric hold
  • Prisoners
  • University of California employees / students or close associates of any of the key personnel on the study
  • Outpatients and/or patients with chronic illness

Inclusion:

Demographic Criteria

  1. Age: any (no age limit)
  2. Language: any (with the use of interpreting services for obtaining consent)

For the following, the infectious syndromes include meningitis, encephalitis, fever, sepsis, and pneumonia:

Clinical Criteria

  1. Hospital admission or transfer with diagnosis of an presumed infectious syndrome or clinical presentation consisting with an infectious syndrome, as defined below:

    • Meningitis: fever >38°C and abnormal imaging or CSF pleocytosis (CSF white blood cell count (WBC) > 5 /mm^3) +/- stiff neck, +/- headache, +/- seizure
    • Encephalitis: pleocytosis and at least one of the following: altered mental status, seizures, new onset of focal neurologic findings, abnormal EEG, acute brain abnormalities on neuroimaging
  2. No known diagnosis of non-infectious etiology responsible for symptoms
  3. Time of enrollment: within 7 days of onset of symptoms, either initial presentation or acute exacerbation of presumed infectious syndrome.

Specimen Criteria

  1. cerebrospinal fluid available within 7 days of symptom onset AND within 3 days of hospital admission or transfer unless evidence for acute exacerbation as defined by abrupt decline in clinical status, worsening pleocytosis or other laboratory parameters
  2. Minimum of 600 microliters (uL) of clinical sample, stored at 4 degrees Celsius (C) no more than 5 days (ideally frozen in -70 degrees Celsius within 24 hours of collection)
  3. No more than 3 freeze-thaw cycles

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02910037


Locations
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United States, California
University of California, Davis Medical Center
Davis, California, United States, 95616
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
University of California, Los Angeles Medical Center
Los Angeles, California, United States, 90095
University of California, San Francisco Medical Center
San Francisco, California, United States, 94116
United States, Colorado
Children's Hospital Colordao
Denver, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Tennessee
St. Jude Children's Research Hospital
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
University of California, San Francisco
California Initiative to Advance Precision Medicine
Sandler Foundation
Bowes Foundation
Charles and Helen Schwab Foundation
University of California, Davis
University of California, Los Angeles
Children's Hospital Los Angeles
Children's Hospital Colorado
St. Jude Children's Research Hospital
Children's Research Institute
University of California, Berkeley
DNAnexus, Inc.
Syapse, Inc.
Investigators
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Principal Investigator: Charles Y Chiu, MD, PhD University of California, San Francisco
Study Director: Hannah Sample, BS University of California, San Francisco

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT02910037     History of Changes
Other Study ID Numbers: P0509948
First Posted: September 21, 2016    Key Record Dates
Last Update Posted: April 13, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All genomic / metagenomic sequencing data from this study will be made available either at NIH Sequence Read Archive or NIH database of Genotypes and Phenotypes (dbGaP), depending on whether human sequence data is included. The investigators intend to make de-identified ancillary clinical, laboratory, and radiographic data available as well upon request.
Supporting Materials: Clinical Study Report (CSR)
Time Frame: The clinical study report will be submitted for publication by June 2018.
URL: http://nextgendiagnostics.ucsf.edu/our-research/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by University of California, San Francisco:
metagenomic next-generation sequencing
microbiological diagnosis
bacterial infections
viral infections
fungal infections
parasitic infections

Additional relevant MeSH terms:
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Meningitis
Encephalitis
Communicable Diseases
Infection
Central Nervous System Diseases
Nervous System Diseases
Brain Diseases