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

Pneumonia, Viral Clinical Trial

— PICKUP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04047719
• Other study ID #: KDC-010
• Status: Completed
• Start date: November 5, 2019
• Est. completion date: June 6, 2022

Study information

• Verified date: February 2023
• Source: Karius, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 257
• Est. completion date: June 6, 2022
• Est. primary completion date: June 6, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Immunocompromised Host
• Pneumonia
• Pneumonia Cavitary
• Pneumonia Fungal
• Pneumonia, Bacterial
• Pneumonia, Viral

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado Denver	Aurora	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University	Durham	North Carolina
United States	MD Anderson Cancer Center	Houston	Texas
United States	Tulane Section of Infectious Disease	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	UCSF Department of Medicine	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Karius, Inc.	Duke Clinical Research Institute

Country where clinical trial is conducted

United States, 

References & Publications (8)

Alix-Panabieres C, Pantel K. Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy. Cancer Discov. 2016 May;6(5):479-91. doi: 10.1158/2159-8290.CD-15-1483. Epub 2016 Mar 11. — View Citation

Blauwkamp TA, Thair S, Rosen MJ, Blair L, Lindner MS, Vilfan ID, Kawli T, Christians FC, Venkatasubrahmanyam S, Wall GD, Cheung A, Rogers ZN, Meshulam-Simon G, Huijse L, Balakrishnan S, Quinn JV, Hollemon D, Hong DK, Vaughn ML, Kertesz M, Bercovici S, Wilber JC, Yang S. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol. 2019 Apr;4(4):663-674. doi: 10.1038/s41564-018-0349-6. Epub 2019 Feb 11. — View Citation

Chen CS, Boeckh M, Seidel K, Clark JG, Kansu E, Madtes DK, Wagner JL, Witherspoon RP, Anasetti C, Appelbaum FR, Bensinger WI, Deeg HJ, Martin PJ, Sanders JE, Storb R, Storek J, Wade J, Siadak M, Flowers ME, Sullivan KM. Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2003 Sep;32(5):515-22. doi: 10.1038/sj.bmt.1704162. — View Citation

Evans SE, Ost DE. Pneumonia in the neutropenic cancer patient. Curr Opin Pulm Med. 2015 May;21(3):260-71. doi: 10.1097/MCP.0000000000000156. — View Citation

Harris B, Geyer AI. Diagnostic Evaluation of Pulmonary Abnormalities in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation. Clin Chest Med. 2017 Jun;38(2):317-331. doi: 10.1016/j.ccm.2016.12.008. — View Citation

Hohenthal U, Itala M, Salonen J, Sipila J, Rantakokko-Jalava K, Meurman O, Nikoskelainen J, Vainionpaa R, Kotilainen P. Bronchoalveolar lavage in immunocompromised patients with haematological malignancy--value of new microbiological methods. Eur J Haematol. 2005 Mar;74(3):203-11. doi: 10.1111/j.1600-0609.2004.00373.x. — View Citation

Norton ME, Baer RJ, Wapner RJ, Kuppermann M, Jelliffe-Pawlowski LL, Currier RJ. Cell-free DNA vs sequential screening for the detection of fetal chromosomal abnormalities. Am J Obstet Gynecol. 2016 Jun;214(6):727.e1-6. doi: 10.1016/j.ajog.2015.12.018. Epub 2015 Dec 18. — View Citation

Schuster MG, Cleveland AA, Dubberke ER, Kauffman CA, Avery RK, Husain S, Paterson DL, Silveira FP, Chiller TM, Benedict K, Murphy K, Pappas PG. Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ Transplant Infection Project, a Multicenter, Prospective, Cohort Study. Open Forum Infect Dis. 2017 Mar 22;4(2):ofx050. doi: 10.1093/ofid/ofx050. eCollection 2017 Spring. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Additive clinical diagnostic value	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.	7 days