Immunocompromised Host, Infectious Diseases, Opportunistic Infections
Conditions
Keywords
Metagenomic Sequencing, Microbial Cell-Free DNA, Karius Spectrum, Infectious Disease Diagnostics, Precision Diagnostics, Real-World Evidence, Observational Registry, Immunocompromised Host, Hematologic Malignancy, Solid Organ Transplant, Stem Cell Transplant, Opportunistic Infection, Diagnostic Stewardship, Clinical Decision Making, Healthcare Utilization
Brief summary
The AXIS Network is a prospective, multicenter observational registry designed to generate real-world evidence on the use of metagenomic sequencing in clinical practice across a broad range of patient populations, infectious disease syndromes, and clinical care settings. Participants receiving routine clinical care at participating institutions may be enrolled into cohort-specific registries that evaluate how metagenomic sequencing is used for diagnostic evaluation, surveillance of high-risk populations, or longitudinal monitoring of treatment response. The study does not assign participants to any intervention, alter standard clinical care, or require study-mandated testing or treatment. Instead, it collects clinical information generated during routine care, including diagnostic testing, antimicrobial use, clinical management decisions, healthcare utilization, and clinical outcomes. The primary objective of AXIS is to evaluate how metagenomic sequencing informs clinical decision-making and is associated with downstream management and clinical outcomes. Secondary objectives include characterization of test utilization patterns, diagnostic integration, antimicrobial management decisions, healthcare utilization, and longitudinal monitoring strategies. Data collected through AXIS may also support development of predictive models and clinical decision-support tools.
Detailed description
The AXIS Network is a prospective, multicenter observational registry designed to evaluate the real-world use of metagenomic sequencing across the infectious disease care continuum. The registry serves as a scalable platform for generating real-world evidence regarding how sequencing-based infectious disease diagnostics are utilized in clinical practice and how diagnostic information influences patient management and outcomes. AXIS is structured as a master protocol with modular cohort appendices that allow evaluation of metagenomic sequencing across diverse patient populations, clinical syndromes, care settings, specimen types, and clinical use contexts. Cohorts may include participants undergoing metagenomic sequencing as part of routine clinical care, participants receiving usual-care diagnostic testing without sequencing, or both, depending on the objectives of the specific cohort. The registry is designed to evaluate metagenomic sequencing in several clinical contexts, including: Diagnostic evaluation of patients with suspected infection Surveillance of populations at increased risk for infection Longitudinal monitoring of treatment response or recurrent infection AXIS places particular emphasis on immunocompromised populations, including patients with hematologic malignancies, solid organ transplant recipients, hematopoietic stem cell transplant recipients, individuals receiving immunosuppressive therapies, and other high-risk populations. Both adult and pediatric participants may be enrolled, depending on cohort-specific eligibility criteria. No study-mandated interventions, treatments, or diagnostic procedures are performed. All diagnostic testing and clinical management decisions are made by treating clinicians according to routine clinical practice. Data are collected through a combination of standardized case report forms and structured extraction of electronic health record data. Data collected may include: Demographic and baseline clinical characteristics Diagnostic testing and timing of results Antimicrobial administration and management decisions Procedures and healthcare utilization Clinical outcomes, including mortality and readmissions Longitudinal follow-up information, where applicable The primary objective of AXIS is to evaluate how metagenomic sequencing informs clinical decision-making and its association with downstream management decisions and clinical outcomes across defined cohorts. Secondary objectives include: Characterizing real-world utilization patterns of metagenomic sequencing Describing integration of sequencing results into diagnostic evaluation Evaluating infection-related clinical management decisions associated with sequencing results Assessing longitudinal monitoring and surveillance applications Evaluating healthcare utilization outcomes Exploratory objectives include assessment of patient-centered outcomes, development of predictive models and clinical decision-support approaches, and establishment of an interactome biobank utilizing residual clinical specimens where permitted. Approximately 50 sites in the United States are expected to participate. The registry is designed to enroll up to approximately 10,000 participants over a planned study duration of approximately seven years. Data generated through AXIS are intended to improve understanding of how metagenomic sequencing is used in routine clinical practice and to inform future research, clinical care strategies, and diagnostic innovation.
Interventions
None listed
Sponsors
Karius, Inc.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant receives care at a participating AXIS site. * Participant meets eligibility criteria for at least one active AXIS cohort as defined in the applicable cohort appendix. * Participant or legally authorized representative is able to provide informed consent, unless waived by the reviewing IRB.
Exclusion criteria
* Any condition that, in the opinion of the investigator, would make participation inappropriate or prevent completion of required study procedures. * Additional cohort-specific
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Antimicrobial Modification Following Karius Spectrum Result Availability | From Karius Spectrum result availability through hospital discharge and up to 90 days following discharge (not to exceed 12 months). | Time from Karius Spectrum result availability to first antimicrobial modification, including initiation, escalation, de-escalation, discontinuation, change in route of administration, or change in duration of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Antimicrobial Modification | From enrollment through 90 days following discharge from the index hospitalization, up to 12 months | Proportion of participants with at least one antimicrobial modification, including initiation, escalation, de-escalation, discontinuation, change in route of administration, or change in duration of therapy. |
| Number of Infection-Directed Microbiological Diagnostic Tests | From Time Zero through discharge from the index hospitalization, up to 12 months | Number of infection-directed microbiological diagnostic tests performed during the index encounter, summarized by test type. |
| Invasive Diagnostic Procedures Ordered Following Karius Spectrum Result Availability | From Karius Spectrum result availability through discharge from the index hospitalization, up to 12 months | Number of invasive diagnostic procedures ordered following Karius Spectrum result availability, summarized by procedure type. |
| Hospital Length of Stay From Admission | During the index hospitalization, from admission through discharge, up to 12 months | Hospital length of stay calculated as the number of days from admission to discharge from the index hospitalization. |
| Incidence of Intensive Care Unit Transfer | During the index hospitalization, from admission through discharge, up to 12 months | Proportion of participants who experience transfer to an intensive care unit during the index hospitalization. |
| Incidence of Mechanical Ventilation | During the index hospitalization, from admission through discharge, up to 12 months | Proportion of participants requiring mechanical ventilation during the index hospitalization. |
| In-Hospital Mortality | During the index hospitalization, from admission through discharge, up to 12 months | Incidence of mortality during the index hospitalization. |
| 30-Day Mortality | Through 30 days following hospital discharge. | Incidence of mortality within 30 days following hospital discharge. |
| 30-Day Readmission | Through 30 days following hospital discharge. | Incidence of hospital readmission within 30 days following hospital discharge. |
| Clostridioides difficile Infection | Enrollment through 30 days following hospital discharge. | Incidence of Clostridioides difficile infection during the study period. |
| Immunosuppressive Therapy Modifications | Baseline through 30 days following hospital discharge. | Proportion of participants with any immunosuppressive therapy modification within a specified timeframe following usual-care or Karius Spectrum result availability. |
| Species-Level Pathogen Identification by Karius Spectrum Compared With Usual Care | From Time Zero through discharge from the index hospitalization, up to 12 months | Proportion of participants with a Karius Spectrum identification at the species level for which usual-care diagnostic testing has no corresponding detection or only a genus-level detection. |
| Antimicrobial Days | From enrollment through 90 days following discharge from the index hospitalization, up to 12 months | Number of days of antimicrobial therapy, summarized by antimicrobial spectrum, antimicrobial type, and route of administration. |
| Number of Diagnostic Imaging Studies | From Time Zero through discharge from the index hospitalization, up to 12 months | Number of diagnostic imaging studies performed during the index encounter, summarized by imaging type. |
| Number of Invasive Diagnostic Procedures | From Time Zero through discharge from the index hospitalization, up to 12 months | Number of invasive diagnostic procedures performed during the index encounter, including procedures such as needle aspiration and bronchoscopy. |
| Invasive Diagnostic Procedures Cancelled Following Karius Spectrum Result Availability | From Karius Spectrum result availability through discharge from the index hospitalization, up to 12 months | Number of invasive diagnostic procedures cancelled following Karius Spectrum result availability, summarized by procedure type. |
| Hospital Length of Stay From Time Zero | From Time Zero through discharge from the index hospitalization, up to 12 months | Hospital length of stay calculated as the number of days from Time Zero to discharge from the index hospitalization. |
| Timing of Intensive Care Unit Transfer Relative to Time Zero | During the index hospitalization, from admission through discharge, up to 12 months | Timing of intensive care unit transfer relative to Time Zero among participants who experience an ICU transfer, characterized according to whether transfer occurs before or after Time Zero. |
| Timing of Mechanical Ventilation Relative to Time Zero | During the index hospitalization, from admission through discharge, up to 12 months | Timing of initiation of mechanical ventilation relative to Time Zero among participants requiring mechanical ventilation, characterized according to whether initiation occurs before or after Time Zero. |
| Ventilator Days | During the index hospitalization, from initiation of mechanical ventilation through discontinuation or discharge, up to 12 months | Number of ventilator-days among participants requiring mechanical ventilation. |
Contacts
CONTACTKat Kwiatkowsi
CONTACTMona Mughar
PRINCIPAL_INVESTIGATORKat Kwiatkowski, PhD
Karius, Inc.
Outcome results
None listed