This clinical trial is designed to evaluate if 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 leads to faster infection diagnosis and treatment. Participants will give a blood sample one time to be used for the testing. Information about the participant's illness and any treatments within 30 days following enrollment will be recorded.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
2,000
Karius Spectrum metagenomic plasma-based test.
University of California San Francisco
San Francisco, California, United States
NOT_YET_RECRUITINGOchsner Medical Center
New Orleans, Louisiana, United States
RECRUITINGBrigham and Women's Hospital
Boston, Massachusetts, United States
RECRUITINGBeth Israel Deaconess Medical Center
Boston, Massachusetts, United States
RECRUITINGUniversity of Nebraska Medical Center
Omaha, Nebraska, United States
RECRUITINGMontefiore Medical Center
New York, New York, United States
NOT_YET_RECRUITINGTime to Identification of a Pathogen Specific Etiology
For each cohort, to evaluate whether the addition of Karius Spectrum testing to usual care testing reduces the time to identification of a pathogen-specific etiology, compared to usual care testing alone, in participants with suspected infection in the outpatient setting.
Time frame: The study sample will be collected within 24 hours of enrollment; participant information including usual care laboratory testing and treatments will be collected for 30 days following enrollment.
Time to Pathogen-Directed Treatment
For each cohort, to evaluate whether the addition of the Karius Spectrum test to usual care testing reduces the time to pathogen-directed treatment compared to usual care testing alone.
Time frame: The study sample will be collected within 24 hours of enrollment; participant information including usual care laboratory testing and treatments will be collected for 30 days following enrollment.
Duration of Antimicrobial Therapy
For each cohort, to evaluate whether the addition of Karius Spectrum testing to usual care reduces the total duration of antimicrobial therapy during the 30-day follow-up period, using data abstracted from the electronic medical record (e.g., medication administration records and provider documentation).
Time frame: 30 days following enrollment.
Percentage of participants receiving pathogen-directed treatment
For each cohort, to evaluate whether the addition of Karius Spectrum testing to usual care testing increases the proportion of participants ultimately receiving pathogen-directed treatment compared to usual care testing alone at specific time points (e.g., Day 3, Day 7, Day 14).
Time frame: 30 days following enrollment.
Time to Clinically Meaningful Detection (CMD)
For each cohort, to evaluate whether the addition of Karius Spectrum testing to usual care testing is associated with a reduction in time to clinically meaningful detection (CMD) compared to usual care testing alone. A CMD event is defined as the earliest identification of either (1) an etiological pathogen, or (2) a non-etiological pathogen that prompts a clinically meaningful action (e.g., treatment initiation, specialist referral, diagnostic escalation, or vascular access removal). Only the first qualifying CMD event per participant will be used for analysis.
Time frame: The study sample will be collected within 24 hours of enrollment; participant information including usual care laboratory testing and treatments will be collected for 30 days following enrollment.
Number of Adverse Events
For all cohorts, the number of participants experiencing adverse events (AEs) and serious adverse events (SAEs) that are unexpected or related to the Karius Spectrum test or study procedures will be assessed. Events will be summarized by type, severity, and relationship to the study intervention.
Time frame: All AEs/SAEs will be collected from the time of blood draw through Day 30.
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