Platelet Immune Responses in Aging and Influenza and Sepsis (INVACS)

NCT03010410 | Unknown

• 1 other identifier: 1040298
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Aging is associated with immunosenescence and impaired host defense mechanisms, contributing to influenza-related morbidity and mortality. Preliminary data demonstrate that the platelet transcriptome is markedly different between healthy subjects and influenza patients. Interferon-induced transmembrane proteins (IFITM) family members are among the transcripts significantly increased in platelets during influenza and expression of IFITM-3 is impaired in elderly subjects, a pattern associated with increased mortality. This study will build on these data and investigate if aging influences the expression of platelet IFITM family members in patients with influenza and sepsis. This study will prospectively determine if aging alters the induction of (IFITMs) in platelets from hospitalized influenza and sepsis patients. The study will also determine if diminished expression of IFITM family members correlates with an increased risk of adverse outcomes in older influenza and sepsis patients.

Conditions

Sepsis; Influenza

Outcome Measures

Primary Outcomes (1)

• 90 day mortality

  For the increased risk of mortality outcome, 90-day mortality will be the primary outcome variable. This will be modeled using mixed effects logistic regression, using days 0, 3, and 7 as repeated measurements. In this fashion, IFITM-3 and mortality are time-varying. A separate model will be fitted for the younger and older groups, since age group is expected to be collinear with IFITM-3 protein.

  90 days

Secondary Outcomes (3)

• 28 day mortality

  28 days

• Interferon-induced transmembrane protein expression in platelets

  24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90

• IFITM-3 mRNA

  24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.

Study Arms (4)

Influenza/respiratory virus pts <65 yrs

Patients with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses

Influenza/respiratory virus pts ≥ 65 yrs

Patients with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses

Sepsis/septic shock patients < 65 yrs

Sepsis and septic shock patients

Sepsis/septic shock patients ≥ 65 yrs

sepsis and septic shock patients

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

This will be a prospective observational cohort study comparing older (age≥65) and younger (age\<65) influenza and sepsis patients.

You may qualify if:

• ≥18 years old at the time of enrollment
• Meet one of the following three main criteria:
• A. INFLUENZA (AND OTHER RESPIRATORY VIRUS) PATIENTS:
• Patients admitted to the intensive care unit (ICU) with a primary microbiologic diagnosis of influenza (any strain) or other routinely clinically identified respiratory viruses within 1 week of symptom onset. Influenza or other respiratory virus will be diagnosed using an RT-PCR viral panel on a respiratory tract specimen, as is currently standard of care on patients admitted to the ICUs at IMC with respiratory symptoms.
• B. SEPSIS PATIENTS:
• Sepsis patients must have
• Suspected or confirmed infection
• AND
• Organ dysfunction as defined by a SOFA \>= 2 above baseline (if no baseline data available, SOFA assumed to be 0)
• C. SEPTIC SHOCK PATIENTS:
• AFTER INFUSION OF 20ML/KG CRYSTALLOID OR EQUIVALENT, Septic shock patients must have
• Suspected or confirmed infection
• AND
• Lactate \> 2 mmol/L
• AND

You may not qualify if:

• Have a congenital or acquired immunodeficiency disorder (e.g., chronic variable immune deficiency, agammaglobulinemia, hypogammaglobulinemia, leukocyte adhesion defects, IgA deficiency, etc.)
• Have neutropenia (\<1,000/mm3)
• Have received immunosuppressant medications within the previous 30 days (e.g., prednisone or prednisone equivalent at a dose≥10mg daily for ≥14 days or any cyclosporine, TNF-alpha antagonists, tacrolimus, sirolimus, interferons, mycophenolate, biological agents, methotrexate, azathioprine, polyclonal/monoclonal antibodies, etc.)
• Have any history of bone marrow or organ transplantation
• Have an active malignancy (not including non-melanoma skin cancer or localized prostate cancer), or have received chemotherapy drugs within the last 6 months.
• Have been admitted to the ICU for greater than 72 hours
• Have a Hemoglobin level \<7gm/dl
• Have clinically significant bleeding

Sponsors & Collaborators

• Intermountain Health Care, Inc.: lead
• University of Utah: collaborator

Study Sites (1)

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

The study will bank remaining platelet lysates for future assays.

MeSH Terms

Conditions

Sepsis; Influenza, Human

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Samuel M Brown, MD MS

  Intermountain Health Care, Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Center for Humanizing Critical Care

Study Record Dates

• First Submitted: January 3, 2017
• First Posted: January 5, 2017
• Study Start: December 21, 2014
• Primary Completion: October 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)