Next Generation Pathogen Sequencing for Prediction of Adverse Events

• ClinicalTrials.gov Identifier: NCT03226158
• Recruitment Status: Active, not recruiting
• First Posted: July 21, 2017
• Last Update Posted: March 30, 2023
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: Karius, Inc.
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Study Description

Brief Summary:

The majority of children and adolescents diagnosed with cancer will experience one or more episodes of fever or infection during their course of therapy. The most common microbiologically documented infection is bloodstream infection (BSI), which can be associated with severe sepsis or death. Current methods of diagnosis require a significant load of live bacteria in the blood making early detection difficult. Delayed diagnosis and delayed optimal therapy of BSIs are associated with increased morbidity and mortality.

This study seeks to identify whether next generation sequencing (NGS) of pathogens can identify patients with impending bloodstream infection. This would enable preemptive targeted therapy to replace antibacterial prophylaxis which often leads ot high-density broad-spectrum antibiotic exposure and contributes to subsequent development of antibiotic resistance.

PRIMARY OBJECTIVE:

• To estimate the sensitivity and specificity of next generation pathogen sequencing for prediction of bloodstream infection in children with cancer at high risk of infection.

Condition or disease
Bloodstream Infection

Detailed Description:

Plasma samples collected but not required for clinical care (discarded samples) will be collected and stored. Results of NGS will be compared between patients who develop BSI immediately (within 72 hours) after sample collection, those who develop other infectious syndromes, and those who remain well. Clinical data describing baseline information about the patient and malignancy, antibiotic and chemotherapy exposure, microbiology testing, hematology results, and infection-related events will be collected prospectively from the electronic medical record.

An initial exploratory phase will examine approximately 50 participants to determine whether the effectiveness of predicting infections. The study may then enroll up to 200 participants to collection additional data for analysis.

Study Design

• Study Type: Observational
• Actual Enrollment: 160 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Prediction of Adverse Events in Children and Adolescents With Cancer at High Risk of Infection (PREDSEQ)
• Actual Study Start Date: August 9, 2017
• Actual Primary Completion Date: March 1, 2022
• Estimated Study Completion Date: December 1, 2023

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Proportion of NGS-positive results [ Time Frame: Once (within 72 hours of enrollment) ]
   To estimate the sensitivity of next generation pathogen sequencing for prediction of BSI, the proportion of NGS-positive results in all positive BSI cultures will be given.
2. Proportion of NGS-negative results [ Time Frame: Once (within 72 hours of enrollment) ]
   To estimate the specificity of next generation pathogen sequencing for prediction of BSI, the proportion of NGS-negative results in all negative BSI cultures will be given.

Biospecimen Retention:   Samples With DNA

Plasma samples collected but not required for clinical care will undergo next generation pathogen sequencing.

Eligibility Criteria

• Ages Eligible for Study: up to 24 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Participants who are being treated at St. Jude Children's Research Hospital and who have a high risk of infection.

Criteria

Inclusion Criteria:

• Under 25 years of age at time of study enrollment
• Undergoing care for cancer at St. Jude
• In a category of patients who are considered by the investigator to be at high risk of infection
• Expected to receive care at St. Jude for at least 7 days

Exclusion Criteria:

• Any condition that would, in the opinion of the investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Contacts and Locations

Locations

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

St. Jude Children's Research Hospital

Karius, Inc.

Investigators

• Principal Investigator: Joshua Wolf, MBBS, BA; St. Jude Children's Research Hospital

More Information

Additional Information:

St. Jude Children's Research Hospital 

Clinical Trials Open at St. Jude 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Goggin KP, Gonzalez-Pena V, Inaba Y, Allison KJ, Hong DK, Ahmed AA, Hollemon D, Natarajan S, Mahmud O, Kuenzinger W, Youssef S, Brenner A, Maron G, Choi J, Rubnitz JE, Sun Y, Tang L, Wolf J, Gawad C. Evaluation of Plasma Microbial Cell-Free DNA Sequencing to Predict Bloodstream Infection in Pediatric Patients With Relapsed or Refractory Cancer. JAMA Oncol. 2020 Apr 1;6(4):552-556. doi: 10.1001/jamaoncol.2019.4120. Erratum In: JAMA Oncol. 2020 Feb 27;:

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT03226158
• Other Study ID Numbers: PREDSEQ
• First Posted: July 21, 2017
• Last Update Posted: March 30, 2023
• Last Verified: March 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:

Next generation pathogen sequencing (NGPS); Pediatric; Cancer; Bloodstream infection (BSI)

Additional relevant MeSH terms:

Infections; Sepsis; Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation