Microbial Cell-free Metagenomic Sequencing for Suspected Infections in Adult Immunocompromised Outpatients

This is a prospective, randomized, controlled interventional trial designed to evaluate the clinical utility and effectiveness of adding the Karius Spectrum™ plasma test to usual care diagnostic tests, compared to usual care testing alone, among immunocompromised participants presenting with suspected infection in the outpatient setting.

The study is structured as a basket trial to enable the efficient evaluation of Karius Spectrum across multiple high-risk clinical populations with shared unmet diagnostic and management needs. The basket protocol outlines core trial elements applicable to all cohorts-including high-level objectives, study design, statistical framework, and operational procedures-while cohort-specific sub-protocols provide detailed rationale, objectives and endpoints, eligibility criteria, and contextual considerations tailored to each cohort. This design supports both pooled analyses across cohorts and subgroup assessments within distinct immunocompromised cohorts.

There are 2 cohorts: Cohort A, which is composed of patients that have had a solid organ transplant; and Cohort B, which is composed of patients that have a hematological malignancy, have had a stem cell transplant, or have undergone CAR-T therapy.

Karius Spectrum is a plasma-based microbial cell-free DNA (mcfDNA) metagenomic sequencing test for agnostic detection, identification, and quantification of more than 1,000 human microbial pathogens (i.e., microorganisms), including bacteria, DNA-based viruses, fungi, and parasites, potentially causing disease anywhere in the body. This test is intended for use in the diagnosis and management of suspected infections.