Pneumonia in the ImmunoCompromised - Use of the Karius Test for the Detection of Undiagnosed Pathogens

Completed

• Conditions: Pneumonia Fungal; Pneumonia, Bacterial; Pneumonia, Viral; Pneumonia Cavitary; Immunocompromised Host
• Interventions: Diagnostic Test: Karius Test

• Registration Number: NCT04047719
• Lead Sponsor: Karius, Inc.

Brief Summary

Given the need for a more sensitive pathogen detection test in patients with immunocompromised pneumonia, this study will evaluate the performance of the Karius Test, a novel NGS blood test for the diagnosis of infectious diseases. We will compare the performance of the Karius Test to the results of microbiologic tests obtained as part of usual care for immunocompromised patients undergoing evaluation for suspected pneumonia.

Detailed Description

Pneumonia is a major cause of morbidity and mortality in highly immunocompromised individuals such as patients with hematologic malignancies and/or hematopoietic stem cell transplant. These patients can be infected by a broad range of potential pathogens, including viral, bacterial, and fungal etiologies and sometimes with multiple pathogens simultaneously. Diagnostic testing often fails to identify a microbial etiology for lower respiratory illness even with bronchoalveolar lavage (BAL). In fact, culture methods, PCR, and antigen testing on BAL samples yields a positive result only 30-67% of the time. Additionally, Idiopathic Pulmonary Syndrome (IPS), a non-infectious pulmonary complication of transplant, can have many overlapping symptoms with infectious pneumonia. Treatment for IPS is administration of steroids which can exacerbate infections. Given these reasons, there is a need for better diagnostics to aid in the management of immunocompromised patients with pneumonia.

Karius has developed a microbial cell-free plasma next-generation sequencing test for pathogen detection capable of detecting \>1,000 organisms including DNA viruses, bacteria, yeasts, molds, and other eukaryotic pathogens. The test is performed in a CLIA-certified/CAP-accredited laboratory with results typically provided within one day from sample receipt. Given the need for a more sensitive diagnostic test for pneumonia in this population, we are evaluating the performance of the Karius Test for pathogen detection.

Study Timeline

• Study First Submitted: 2019-08-05
• Study First Submitted QC: 2019-08-05
• Study First Posted: 2019-08-07
• Study Start: 2019-11-05
• Primary Completion: 2022-06-06
• Study Completion: 2022-06-06
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 257

Inclusion Criteria

Subjects must meet all of the criteria in Section A and all of the criteria in either Section B, Section C or Section D.

Section A:

1. Patient is ≥ 18 years of age.
2. Is currently admitted to the hospital.
3. Has a suspected infectious pneumonia warranting diagnostic evaluation and treatment.
4. Has undergone a diagnostic bronchoscopy for the evaluation of microbiologic etiology of pneumonia within 1 day prior to or has a scheduled bronchoscopy within 5 days following enrollment.
5. Patient or patient's Legally Authorized Representative (LAR) has provided consent for the study.

Section B:

1. Has one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Lymphoma (any type), Multiple Myeloma (MM) or malignant transformation of Chronic Lymphocytic Leukemia (CLL/SLL).

2. Are immunocompromised defined as having at least one of the following:

   1. Received chemotherapy within the last 45 days.
   2. A relapse of hematologic malignancy for which chemotherapy treatment is anticipated within the next 45 days.
   3. ANC<500 for a minimum of 14 days and within 8 weeks prior to enrollment.

Section C:

1. Has undergone autologous hematopoietic stem cell transplantation (e.g. bone marrow transplantation) for one of the following hematologic malignancies: Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), Myelodysplastic Syndrome (MDS), Lymphoma (any type), or Multiple Myeloma (MM);), or malignant transformation of Chronic Lymphocytic Leukemia (CLL/SLL).

2. Are immunocompromised defined as having at least one of the following:

   1. Undergone autologous hematopoietic stem cell transplantation (HSCT) within the past 6 months.
   2. Received chemotherapy within the last 45 days.
   3. A relapse of hematologic malignancy for which chemotherapy treatment is anticipated within the next 45 days.

Section D:

1. Has undergone allogeneic hematopoietic stem cell transplantation (e.g., bone marrow transplantation) for any clinical indication.

2. Are immunocompromised defined as having at least one of the following:

   1. Has undergone hematopoietic stem cell transplantation (HCST) within the past 1 year.
   2. Has active graft versus host disease (GVHD) requiring immunosuppressive pharmacologic treatment.

Exclusion Criteria

1. Patient is moribund and, in the opinion of the treating physician, is not expected to survive >24 hours beyond the time of potential study enrollment visit.
2. Microbiologic etiology of index pneumonia event has already been identified per local Standard of Care testing.
3. Patient was previously enrolled in this study.
4. Patient has any condition that, in the opinion of the treating physician, will prevent the patient from completing the study. (Note: a qualified patient may still enroll in the study if they decline to have exploratory research sample collected.)
5. Patient is positive for SARS-COV-2 by any molecular testing within the 14 days prior to enrollment.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Intent-to-Diagnose Population	Karius Test	All subjects enrolled in the study that have at least one Karius Test with a valid result

Primary Outcome Measures

Name	Time	Method
Additive clinical diagnostic value	7 days	Percent of patients with ≥1 pathogen identified by the Karius Test collected at enrollment that is adjudicated as a probable cause of the subject's index pneumonia event with no pathogen identified as a probable cause of the subject's index pneumonia event from an adjudicated composite of all microbiologic test results performed per Standard of Care with results available within 7 days of study enrollment.

Trial Locations

Locations (10)

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Fred Hutchinson Cancer Center; 🇺🇸 Seattle, Washington, United States

UCSF Department of Medicine; 🇺🇸 San Francisco, California, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of Colorado Denver; 🇺🇸 Aurora, Colorado, United States

Tulane Section of Infectious Disease; 🇺🇸 New Orleans, Louisiana, United States