InfectionOPTIMUMNCT07110636
Microbial Cell-free Metagenomic Sequencing for Suspected Infections in Adult Immunocompromised Outpatients
A study testing Metagenomic plasma-based test for agnostic pathogen detection in people with Infection and Infections, Bacterial, run by Karius, Inc. at 6 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection, Infections, Bacterial, Infections, Fungal
- What is being tested?
- Metagenomic plasma-based test for agnostic pathogen detection
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,000 participants
- Where
- 6 sitesUnited States
- Study dates
- 27 Oct 2025to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Basket Protocol* All participants must meet inclusion
- Age ≥18
- Included in one of the following immunocompromised groups: Solid organ transplant recipient (SOT) on chronic immunosuppression; Diagnosed with hematologic malignancy (HM) and/or recipient of a hematopoietic cell transplant (HCT); Diagnosed with a solid tumor and on specific types of active treatment; Recipient of drugs or novel biologics causing chronic immunosuppression; Diagnosed with an HIV infection; Diagnosed with inborn errors of immunity
- Treating provider suspects infection and plans to obtain usual care diagnostic testing for the suspected infection (i.e., microbiologic testing)
- Willing to provide research samples via blood draw
- Willing and able to provide informed consent
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- Presenting for evaluation in the outpatient setting (includes telehealth)
- For Participants enrolled in Sub-Protocol A- Solid Organ Transplant
- All Sub-Protocol A subjects must meet the following:
- <!-- -->
- Solid organ transplant recipient on transplant immunosuppression Non-lung recipients must meet one or more of the following characteristics: <1 year from transplant; Augmented immunosuppression for suspected or confirmed rejection within the last 6 months; Confirmed systemic infection in last 6 months
- Suspected infection defined by one or more of the syndromes: Cardiac; Lower Respiratory; Gastrointestinal / Hepatobiliary; Genitourinary; Neurologic / Ophthalmologic; Skin / Soft tissue / musculoskeletal; Not Otherwise Specified
- For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant* All Sub-Protocol B subjects must meet the following:
- Is included in at least one of the following groups: Hematologic malignancy (leukemia, myelodysplastic syndrome, lymphoma, multiple myeloma) and at least one of the following: Received chemotherapy or other systemic anti-cancer therapy associated with immunosuppressive effects within 90 days (e.g., monoclonal antibodies associated with B-cell or plasma cell depletion, bi-specific t-cell engagers, BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors) within the last 90 days Note: Checkpoint inhibitors are not included unless given in combination with an immunosuppressive agent; Relapsed disease with chemotherapy anticipated in 60 days; ANC <500 within the last 72 hours; Hypogammaglobulinemia IgG <400 within the last 30 days; Allogeneic stem cell transplant for any clinical indication and at least one of the following: Within 1-year post-transplant; On systemic immunosuppressive therapy for GVHD treatment or prophylaxis; Autologous stem cell transplant for hematologic malignancy and at least one of the following: Within 6 months post-transplant; ANC <500 within the last 72 hours; B cell and plasma cell targeted CAR-T therapy for hematologic malignancy and at least one of the following: Within 6 months of CAR-T cell infusion; CD4 T-cell <200 within the last 30 days; IgG < 400 within the last 30 days; ANC <500 within the last 72 hours; On systemic immunosuppressive therapy for CRS/ICANS
- Suspected infection defined by one or more of the syndromes: Cardiac; Lower Respiratory; Gastrointestinal / Hepatobiliary; Genitourinary; Neurologic / Ophthalmologic; Skin / Soft tissue / musculoskeletal; Not Otherwise Specified
Who cannot join
- Basket Protocol* All participants must not meet the following:
- Active symptoms are likely attributed to non-infectious causes.
- Any other clinically significant medical condition that, in the opinion of the treating provider, makes participation undesirable, including but not limited to severe psychiatric illness, etc.
- For Participants enrolled in Sub-Protocol A- Solid Organ Transplant
- All Sub-Protocol A subjects must not meet the following:
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- Patients who have been previously evaluated (including via telehealth) for the same clinical signs and symptoms at this institution and pathogen-directed usual care (UC), diagnostic testing was ordered during that prior encounter, with one or more diagnostic test results still pending.
- Patients with a suspected or confirmed primary upper respiratory infection (e.g., viral pharyngitis, sinusitis, or uncomplicated bronchitis) unless there is clinical suspicion of a concurrent lower respiratory or systemic infection requiring further diagnostic evaluation.
- For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant* All Sub-Protocol B subjects must not meet the following:
- Patients that have been previously evaluated (including via telehealth) for the same clinical signs and symptoms at this institution and pathogen-directed usual care (UC) diagnostic testing was ordered during that prior encounter with one or more diagnostic tests results still pending.
- Patients with a suspected or confirmed primary upper respiratory infection (e.g., viral pharyngitis, sinusitis, or uncomplicated bronchitis) unless there is clinical suspicion of a concurrent lower respiratory or systemic infection requiring further diagnostic evaluation.
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ann Woolley, MD, AWOOLLEY@bwh.harvard.edu
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Audrey H Mahajan, MD, 617-632-7706, amahaja1@bidmc.harvard.edu
Dimitrios Farmakiotis, MD, (617) 632-7706, dfarmaki@bidmc.harvard.edu
- Recruiting
Ochsner Medical Center
New Orleans, Louisiana, 70121
Jonathan Hand, MD, jonathan.hand@ochsner.org
Julie Castex, MSN, jcastex@ochsner.org
- Not yet recruiting
Montefiore Medical Center
New York, New York, 10467
Margaret McCort, MD, mnewmanmcc@montefiore.org
- Recruiting
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Carlos Gomez, MD, 402-559-8650, carlosgomez@unmc.edu
Carlos Gomez, MA
- Not yet recruiting
University of California San Francisco
San Francisco, California, 94143
Monica Fung, MD, Monica.Fung@ucsf.edu
About this study
Official title: A Prospective Randomized Basket Trial Evaluating the Clinical Utility of Plasma-based Microbial Cell-free Metagenomic Sequencing for Diagnosis and Management of Suspected Infections in Adult Immunocompromised Outpatients
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.
Read the detailed description
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.
- Being tested
- Metagenomic plasma-based test for agnostic pathogen detection
- Keywords
- Karius, Karius Spectrum, Infection detection, metagenomic testing, Pathogen detection, Bacterial Infection, Fungal Infection, Parasitic Infection, Viral Infection
- Medical subject headings
- Infections, Bacterial Infections, Mycoses, Virus Diseases, Parasitic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metagenomic plasma-based test for agnostic pathogen detectionDiagnostic test
Karius Spectrum metagenomic plasma-based test.
| Study group | Role | What they receive |
|---|---|---|
| Interventional | Experimental | This arm will receive Karius Spectrum test results. Receives: Diagnostic Test: Metagenomic plasma-based test for agnostic pathogen detection |
| Control | No intervention | This arm will not receive Karius Spectrum test results. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time 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.
Measured: 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.
Measured: 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.
Secondary outcomes (4)
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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: All AEs/SAEs will be collected from the time of blood draw through Day 30.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2025
- Study start27 Oct 2025
- Primary completion15 Sep 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for InfectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Model description
- Both the interventional group and control group will undergo a blood draw. The interventional group will receive Karius Spectrum test results. The control group will not receive Karius Spectrum test results.
- Masking
- None (open label)
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karius, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kat Kwiatkowski, PhD, Principal investigator, Karius, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07110636
- Sponsor's protocol ID
- KAR-0025
- Acronym
- OPTIMUM
- Status last verified
- Jan 2026
- First submitted
- 17 Jun 2025
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Randomized Basket Trial Evaluating the Clinical Utility of Plasma-based Microbial Cell-free Metagenomic Sequencing for Diagnosis and Management of Suspected Infections in Adult Immunocompromised Outpatients
- ClinicalTrials.gov ID
- NCT07110636
- Acronym / sponsor ID
- OPTIMUM / KAR-0025
- Keywords
- Karius, Karius Spectrum, Infection detection, metagenomic testing, Pathogen detection, Bacterial Infection, Fungal Infection, Parasitic Infection
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Karius, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Oct 2025 (actual)
- Primary completion
- 15 Sep 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 7 Aug 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Both the interventional group and control group will undergo a blood draw. The interventional group will receive Karius Spectrum test results. The control group will not receive Karius Spectrum test results.
| Arm | Type | Receives |
|---|---|---|
| Interventional | Experimental | Diagnostic Test: Metagenomic plasma-based test for agnostic pathogen detectionThis arm will receive Karius Spectrum test results. |
| Control | No intervention | –This arm will not receive Karius Spectrum test results. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Basket Protocol* All participants must meet inclusion
- For Participants enrolled in Sub-Protocol A- Solid Organ Transplant
- <!-- -->
- For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant* All Sub-Protocol B subjects must meet the following:
Key exclusion criteria (11 listed)
- Basket Protocol* All participants must not meet the following:
- For Participants enrolled in Sub-Protocol A- Solid Organ Transplant
- <!-- -->
- For Participants enrolled in Sub-Protocol B- Hematological Malignancies and Transplant* All Sub-Protocol B subjects must not meet the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metagenomic plasma-based test for agnostic pathogen detectionKarius Spectrum metagenomic plasma-based test. | Diagnostic test | Interventional |
Primary outcome
Time to Identification of a Pathogen Specific Etiology
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.
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 to Pathogen-Directed Treatment
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.
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.
4 secondary outcomes
Duration of Antimicrobial Therapy
Time frame: 30 days following enrollment.
Percentage of participants receiving pathogen-directed treatment
Time frame: 30 days following enrollment.
Time to Clinically Meaningful Detection (CMD)
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
Time frame: All AEs/SAEs will be collected from the time of blood draw through Day 30.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kat Kwiatkowski, PhD principal investigator
Karius, Inc.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Metagenomic plasma-based test for agnostic pathogen detection in people with Infection and Infections, Bacterial, run by Karius, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kat Kwiatkowski, PhD (866-452-7487, kat.kwiatkowski@kariusdx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Identification of a Pathogen Specific Etiology (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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2026.