Metagenomic Sequencing Across the Infectious Disease Risk and Care Continuum (AXIS)

A Prospective, Multicenter Registry to Evaluate Metagenomic Sequencing Across the Infectious Disease Risk and Care Continuum

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Infectious Diseases; Opportunistic Infections; Immunocompromised Host

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.

• Study Type: Observational
• Enrollment (Estimated): 10000

Contacts and Locations

• Study Contact: Name: Kat Kwiatkowsi; Phone Number: 910-232-6396; Email: kat.kwiatkowski@kariusdx.com
• Study Contact Backup: Name: Mona Mughar; Phone Number: 8653082690; Email: mona.mughar@kariusdx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants receiving routine clinical care at participating institutions who meet eligibility criteria for one or more active AXIS cohorts. Cohorts may evaluate metagenomic sequencing for diagnostic evaluation, surveillance, or longitudinal monitoring across a range of infectious disease syndromes, patient populations, and healthcare settings.

This approach prevents you from having to amend the NCT record every time AXIS expands beyond hospitalized immunocompromised patients with lower respiratory infections. It also aligns with how platform registries and master protocols are typically registered.

Description

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 exclusion criteria may apply and are defined within the applicable cohort appendix.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Hospitalized Immunocompromised Adults With Suspected Lower Respiratory Infection; Hospitalized immunocompromised adults with clinical evidence of lower respiratory infection who undergo Karius Spectrum plasma microbial cell-free DNA metagenomic sequencing as part of routine clinical care. Participants are enrolled in a prospective observational registry and are not assigned to any study-directed intervention. Clinical data are collected through routine care and electronic health record review to evaluate associations between metagenomic sequencing results, antimicrobial management decisions, diagnostic testing utilization, healthcare utilization, and clinical outcomes. Participants are followed through hospital discharge and for up to 90 days following discharge, not to exceed 12 months total follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Antimicrobial Modification Following Karius Spectrum Result Availability	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.	From Karius Spectrum result availability through hospital discharge and up to 90 days following discharge (not to exceed 12 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Antimicrobial Modification	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.	From enrollment through 90 days following discharge from the index hospitalization, up to 12 months
Number of Infection-Directed Microbiological Diagnostic Tests	Number of infection-directed microbiological diagnostic tests performed during the index encounter, summarized by test type.	From Time Zero through discharge from the index hospitalization, up to 12 months
Invasive Diagnostic Procedures Ordered Following Karius Spectrum Result Availability	Number of invasive diagnostic procedures ordered following Karius Spectrum result availability, summarized by procedure type.	From Karius Spectrum result availability through discharge from the index hospitalization, up to 12 months
Hospital Length of Stay From Admission	Hospital length of stay calculated as the number of days from admission to discharge from the index hospitalization.	During the index hospitalization, from admission through discharge, up to 12 months
Incidence of Intensive Care Unit Transfer	Proportion of participants who experience transfer to an intensive care unit during the index hospitalization.	During the index hospitalization, from admission through discharge, up to 12 months
Incidence of Mechanical Ventilation	Proportion of participants requiring mechanical ventilation during the index hospitalization.	During the index hospitalization, from admission through discharge, up to 12 months
In-Hospital Mortality	Incidence of mortality during the index hospitalization.	During the index hospitalization, from admission through discharge, up to 12 months
30-Day Mortality	Incidence of mortality within 30 days following hospital discharge.	Through 30 days following hospital discharge.
30-Day Readmission	Incidence of hospital readmission within 30 days following hospital discharge.	Through 30 days following hospital discharge.
Clostridioides difficile Infection	Incidence of Clostridioides difficile infection during the study period.	Enrollment through 30 days following hospital discharge.
Immunosuppressive Therapy Modifications	Proportion of participants with any immunosuppressive therapy modification within a specified timeframe following usual-care or Karius Spectrum result availability.	Baseline through 30 days following hospital discharge.
Species-Level Pathogen Identification by Karius Spectrum Compared With Usual Care	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.	From Time Zero through discharge from the index hospitalization, up to 12 months
Antimicrobial Days	Number of days of antimicrobial therapy, summarized by antimicrobial spectrum, antimicrobial type, and route of administration.	From enrollment through 90 days following discharge from the index hospitalization, up to 12 months
Number of Diagnostic Imaging Studies	Number of diagnostic imaging studies performed during the index encounter, summarized by imaging type.	From Time Zero through discharge from the index hospitalization, up to 12 months
Number of Invasive Diagnostic Procedures	Number of invasive diagnostic procedures performed during the index encounter, including procedures such as needle aspiration and bronchoscopy.	From Time Zero through discharge from the index hospitalization, up to 12 months
Invasive Diagnostic Procedures Cancelled Following Karius Spectrum Result Availability	Number of invasive diagnostic procedures cancelled following Karius Spectrum result availability, summarized by procedure type.	From Karius Spectrum result availability through discharge from the index hospitalization, up to 12 months
Hospital Length of Stay From Time Zero	Hospital length of stay calculated as the number of days from Time Zero to discharge from the index hospitalization.	From Time Zero through discharge from the index hospitalization, up to 12 months
Timing of Intensive Care Unit Transfer Relative to Time Zero	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.	During the index hospitalization, from admission through discharge, up to 12 months
Timing of Mechanical Ventilation Relative to Time Zero	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.	During the index hospitalization, from admission through discharge, up to 12 months
Ventilator Days	Number of ventilator-days among participants requiring mechanical ventilation.	During the index hospitalization, from initiation of mechanical ventilation through discontinuation or discharge, up to 12 months

Collaborators and Investigators

• Sponsor: Karius, Inc.
• Investigators: Principal Investigator: Kat Kwiatkowski, PhD, Karius, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2033

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: September 12, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 12, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Immunocompromised Host; Hematologic Malignancy; Observational Registry; Stem Cell Transplant; Healthcare Utilization; Solid Organ Transplant; Opportunistic Infection; Diagnostic Stewardship; Clinical Decision Making; Real-World Evidence; Karius Spectrum; Metagenomic Sequencing; Microbial Cell-Free DNA; Infectious Disease Diagnostics; Precision Diagnostics
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Infections; Hematologic Diseases; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Communicable Diseases; Opportunistic Infections
• Other Study ID Numbers: KAR-0040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No