Pediatric Infectious Disease Precision Medicine Using Sequencing Evaluation of CSF (PIPSEC)

• ClinicalTrials.gov Identifier: NCT03796546
• Recruitment Status: Completed
• First Posted: January 8, 2019
• Last Update Posted: November 10, 2020
• Sponsor: IDbyDNA, Inc.
• Collaborator: Rady Children's Hospital, San Diego
• Information provided by (Responsible Party): IDbyDNA, Inc.

Study Description

Brief Summary:

Prospective, multi-site, study to evaluate the diagnosis rate of DNA and RNA sequencing of cerebrospinal fluid for identification of pathogens directly in patients who have already had a spinal tap to evaluate for infection and were found to have a pleocytosis. Diagnostic rate and clinical utility of concurrent standard testing will be compared to diagnostic rate and clinical utility of DNA and RNA sequencing.

Condition or disease
Infection; Meningitis

Detailed Description:

IDbyDNA, Inc. has developed a robust sequencing reference database for viruses, bacteria, fungi and parasites and developed novel analysis methods to analyze next-generation (NGS) sequencing data to rapidly identify infectious agents. This technology suite, known as the Explify™ platform, holds the promise to improve patient care and efficiently guide provider treatment planning for those suffering from infectious disease.

The PIPSEC trial, developed by pediatric physicians specializing in genomic medicine, is intended to facilitate the acquisition of high quality and clinically annotated biospecimens for the purpose of research discovery. This project intends to advance metagenomics, microbial genetics, bioinformatics and data analytics, for pathogen detection utilizing cerebral spinal fluid (CSF) specimens to contribute to the diagnosis of infectious agents impacting the central nervous system among pediatric patients. Clinically annotated specimens will facilitate continued development and validation of the Explify test and its clinical utility for providers treating central nervous system (CNS) infections.

The primary objective is to assess clinical utility of the Explify test compared to concurrent standard of care testing to identify pathogens from CSF fluid within a pediatric patient population.

Study Design

• Study Type: Observational
• Actual Enrollment: 71 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: A Prospective Trial to Investigate the Clinical Utility and Application of a Next Generation Sequencing Test for Pathogen Detection of Cerebral Spinal Fluid (CSF) Samples to Diagnose Pediatric Central Nervous System (CNS) Infections
• Actual Study Start Date: January 22, 2019
• Actual Primary Completion Date: October 7, 2020
• Actual Study Completion Date: October 7, 2020

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Diagnostic Rate [ Time Frame: 24 months ]
   Comparison of the sensitivity, specificity, positive and negative predictive values of IDbyDNA NGS results with the Explify diagnostic platform compared with standard care.

Secondary Outcome Measures :

1. Clinical Utilization [ Time Frame: 24 months ]

   Change of Management resulting from NGS diagnosis versus diagnosis based on standard of care. Change of Management is a binary (yes or no) based on assignments made by the PI or designee at each site using the following domains:

   • Diagnosis specific pharmacological treatment
   • Diagnosis specific management
   • Diagnosis specific supportive interventions A change in any of these domains will be considered a change of clinical management for utilization purposes.

Other Outcome Measures:

1. Post-Hoc Analysis - Economic Evaluation (1) [ Time Frame: 24 months ]

   Economic evaluation of cost of standard of care testing compared to economic cost of NGS testing:

   Determination of what diagnosis made could have been made with best possible clinical tests currently available.

2. Post-Hoc Analysis - Economic Evaluation (2) [ Time Frame: 24 months ]
   Cost analysis of what best available testing would have cost.
3. Post-Hoc Analysis - Host Response [ Time Frame: 24 months ]
   RNA sequencing to determine if there is a specific host response to either specific infectious or noninfectious etiologies.

Biospecimen Retention:   Samples With DNA

Residual cerebrospinal fluid collected for standard of care clinical diagnostic purposes

Eligibility Criteria

• Ages Eligible for Study: 0 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Probability Sample

Study Population

This project will enroll children who are having an evaluation for central nervous system (CNS) infection and have already had a lumbar puncture to obtain cerebrospinal fluid (CSF) to evaluate for infection and host immune response. As such enrolled patients will be undergoing an evaluation for suspected meningitis, encephalitis, ventriculitis and VP shunt infection.

Patients in whom there is CSF remaining after standard testing has been obtained and who meet the other inclusion criteria will be approached for enrollment in the study.

Criteria

Inclusion Criteria:

• Age 0-17 years of age (not yet 18)
• Clinical evaluation for CNS infection
• CSF white blood cell count (WBC) > 15 cells/µL when there are less than 5000 RBCs on same
• Admitted to a participating study site
• CSF obtained per standard protocol
• 1 mL of appropriately stored CSF is available following completion of all standard of care testing

Exclusion Criteria:

• CSF Red blood cell (RBC) count > 5000 cells/µL on same CSF sample as with pleocytosis
• Unable to obtain consent

Contacts and Locations

Locations

United States, California

CHOC Children's Hospital Orange County

Orange, California, United States, 92868

Rady Children's Hospital

San Diego, California, United States, 92123

United States, Florida

Nicklaus Children's Hospital

Miami, Florida, United States, 33155

Sponsors and Collaborators

IDbyDNA, Inc.

Rady Children's Hospital, San Diego

More Information

Additional Information:

Sponsor Website 

• Responsible Party: IDbyDNA, Inc.
• ClinicalTrials.gov Identifier: NCT03796546
• Other Study ID Numbers: PIPSEC - 01
• First Posted: January 8, 2019
• Last Update Posted: November 10, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by IDbyDNA, Inc.:

Pediatric

Additional relevant MeSH terms:

Infections; Meningitis; Central Nervous System Diseases; Nervous System Diseases