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

Sponsor

Karius, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04047719

Collaborator

Duke Clinical Research Institute (Other)

195

Enrollment

Locations

25.9

Anticipated Duration (Months)

19.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Bacterial Pneumonia, Viral Pneumonia Fungal Pneumonia Cavitary Immunocompromised Host	Diagnostic Test: Karius Test

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 Design

Study Type:

Observational

Anticipated Enrollment :

195 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Nov 5, 2019

Anticipated Primary Completion Date :

Sep 30, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Intent-to-Diagnose Population All subjects enrolled in the study that have at least one Karius Test with a valid result	Diagnostic Test: Karius Test Karius Test for detection of microbial cell free DNA (mcfDNA) in plasma

Arm

Intervention/Treatment

Intent-to-Diagnose Population

All subjects enrolled in the study that have at least one Karius Test with a valid result

Diagnostic Test: Karius Test

Karius Test for detection of microbial cell free DNA (mcfDNA) in plasma

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Patient is ≥ 18 years of age.
Is currently admitted to the hospital.
Has a suspected infectious pneumonia warranting diagnostic evaluation and treatment.
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.
Patient or patient's Legally Authorized Representative (LAR) has provided consent for the study.

Section B:

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).
Are immunocompromised defined as having at least one of the following:
Received chemotherapy within the last 45 days.
A relapse of hematologic malignancy for which chemotherapy treatment is anticipated within the next 45 days.
ANC<500 for a minimum of 14 days and within 8 weeks prior to enrollment.

Section C:

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).
Are immunocompromised defined as having at least one of the following:
Undergone autologous hematopoietic stem cell transplantation (HSCT) within the past 6 months.
Received chemotherapy within the last 45 days.
A relapse of hematologic malignancy for which chemotherapy treatment is anticipated within the next 45 days.

Section D:

Has undergone allogeneic hematopoietic stem cell transplantation (e.g., bone marrow transplantation) for any clinical indication.
Are immunocompromised defined as having at least one of the following:
Has undergone hematopoietic stem cell transplantation (HCST) within the past 1 year.
Has active graft versus host disease (GVHD) requiring immunosuppressive pharmacologic treatment.

Exclusion Criteria:

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.
Microbiologic etiology of index pneumonia event has already been identified per local Standard of Care testing.
Patient was previously enrolled in this study.
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.)
Patient is positive for SARS-COV-2 by any molecular testing within the 14 days prior to enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
2	UCSF Department of Medicine	San Francisco	California	United States	94143
3	University of Colorado Denver	Aurora	Colorado	United States	80045
4	Tulane Section of Infectious Disease	New Orleans	Louisiana	United States	70112
5	Weill Cornell Medicine	New York	New York	United States	10021
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	Duke University	Durham	North Carolina	United States	27710
8	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15025
9	MD Anderson Cancer Center	Houston	Texas	United States	77030
10	Fred Hutchinson Cancer Center	Seattle	Washington	United States	98109