Granzyme A in Patients With E. Coli Bacteremic Urinary Tract Infections

NCT03991793 | Unknown

• 1 other identifier: PI19/070
• Study Type: observational
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: Survival in Granzyme A gene (gzmA) knocked-out mice was significantly longer than in wild-type mice in a murine peritonitis model (cecal ligation puncture). Hypothesis: GZM A has a pathogenic role in sepsis in humans and gzmA polymorphisms can help to predict the risk of sepsis among patients with systemic infections (E. coli bacteremic urinary tract infections). Objectives:

• Design and setting: Prospective nested case-control study
• Study population: consecutive adult patients with bacteremic urinary tract infections (UTIs) caused by E. coli
• Exclusion criteria: Patients with conditions that significantly compromise immune status or patients exposed to urologic procedures
• Estimated sample size: 50 patients with a sepsis/ non sepsis 1:1 ratio. Septic and non septic patients will be matched on gender, age (+/- 10 years), comorbidity (Charlson score +/-1), time symptom onset to blood culture (+/- 24h)
• Measurements: GZM A serum levels will be determined on day 0, day 2-3, day 30. GZM A kinetics, gzmA polymorphisms (whole exome sequencing).Whole genome sequencing of E. coli isolates retrieved from blood cultures will be performed.
• Analysis: Association between GZM A levels and gzmA polymorphisms and sepsis will be analyzed adjusting for patient, infection and microorganism-related factors (multivariate analysis).

Conditions

Bloodstream Infection; Sepsis; Pathogenesis; Escherichia Coli Bacteremia

Keywords

Granzyme A; Sepsis; Pathogenesis; Escherichia coli Bloodstream Infection; Immunopathology

Outcome Measures

Primary Outcomes (1)

• Granzyme A serum levels

  GZM A serum concentration (GZM A serum levels) will be determined at day 0 by an ELISA commercial assay (Human Granzyme A ELISA development kit; Mabtech)

  day 0

Secondary Outcomes (2)

• gzmA polymorphisms

  day 0

• Granzyme A serum kinetics

  day 2-3 and day 30

Study Arms (2)

Sepsis

Severe sepsis or septic shock (2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference)

Control

Absence of severe sepsis or septic shock (2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with E. coli bloodstream infection from a urinary source

You may qualify if:

• E. coli bacteremic urinary tract infection

You may not qualify if:

• Immunocompromised hosts: HIV/AIDS, Neutropenia, Solid neoplasia, Hematological neoplasia, patients receiving immunosuppressive therapy
• Systemic antibiotic therapy in the 2 months preceding the bloodstream infection
• Anatomical or functional urological abnormalities that require urological procedures in the previous 2 months

Sponsors & Collaborators

• Instituto de Investigación Sanitaria Aragón: lead

Related Publications (2)

• Arias MA, Jimenez de Bagues MP, Aguilo N, Menao S, Hervas-Stubbs S, de Martino A, Alcaraz A, Simon MM, Froelich CJ, Pardo J. Elucidating sources and roles of granzymes A and B during bacterial infection and sepsis. Cell Rep. 2014 Jul 24;8(2):420-9. doi: 10.1016/j.celrep.2014.06.012. Epub 2014 Jul 10.

  PMID: 25017060 RESULT

• Garcia-Laorden MI, Stroo I, Terpstra S, Florquin S, Medema JP, van T Veer C, de Vos AF, van der Poll T. Expression and Function of Granzymes A and B in Escherichia coli Peritonitis and Sepsis. Mediators Inflamm. 2017;2017:4137563. doi: 10.1155/2017/4137563. Epub 2017 Jun 12.

  PMID: 28694562 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples (serum) for GZM A levels and gzmA polymorphisms E. coli strains

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• José Ramón P Paño-Pardo

  Instituto de Investigación Sanitaria Aragon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José R Paño-Pardo, MD

CONTACT

+34 976 765700; jrpanno@salud.aragon.es

Elena Morte, MD

CONTACT

emromea@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator. Assistant Professor

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 19, 2019
• Study Start: June 20, 2019
• Primary Completion: May 30, 2020
• Study Completion: December 31, 2020
• Last Updated: June 19, 2019

Record last verified: 2019-06