Clinical trial NCT02910037: Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
Official title: Clinical Implementation of Metagenomic Next-Generation Sequencing for Precision Diagnosis of Acute Infectious Diseases; Neuroinflammatory Cohort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Encephalitis
Meningitis
Keywords: metagenomic next-generation sequencing
microbiological diagnosis
bacterial infections
viral infections
fungal infections
parasitic infections
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: California Initiative to Advance Precision Medicine
name: Sandler Foundation
name: Bowes Foundation
name: Charles and Helen Schwab Foundation
name: University of California, Davis
name: University of California, Los Angeles
name: Children's Hospital Los Angeles
name: Children's Hospital Colorado
name: St. Jude Children's Research Hospital
name: Children's National Research Institute
name: University of California, Berkeley
name: DNAnexus, Inc.
name: Syapse, Inc.
First posted: 2016-09-21
Enrollment: 214
Sex: ALL
Minimum age (years): 1
Maximum age (years): 110
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility 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

Primary outcomes:
measure: Total Number of Cases With at Least One Provider Response
timeFrame: within 1 month of patient enrollment in study
Secondary outcomes:
measure: Clinical Outcomes: Time From Cerebrospinal Fluid Collection to mNGS Results
timeFrame: from admission to 1 month post discharge for each patient during the enrollment period of study
measure: Clinical Outcomes: Length of Stay
timeFrame: from admission to 1 month post discharge for each patient during the enrollment period of study
measure: Clinical Outcomes: Final Diagnosis Category
timeFrame: from admission to time of final case review (1 month post discharge or up to one year)
measure: Clinical Outcomes: Concordance of mNGS With Other Molecular Testing on Cerebrospinal Fluid Pathogens
timeFrame: from admission to 1 month post discharge for each patient during the enrollment period of study
Other outcomes:
Locations:
city: Davis
country: United States
facility: University of California, Davis Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Denver
country: United States
facility: Children's Hospital Colordao
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Nashville
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: University of California, San Francisco
name: Charles Y Chiu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: Hannah Sample, BS
role: STUDY_DIRECTOR
References:
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