SepsisNCT03010410
Platelet Immune Responses in Aging and Influenza and Sepsis (INVACS)
An observational study of Sepsis and Influenza, run by Intermountain Health Care, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2014to Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.
Who may be able to join
- ≥18 years old at the time of enrollment
- Meet one of the following three main criteria:
- 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.
- OR
- SEPSIS PATIENTS:
Show all 19Show fewer
- 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)
- OR
- 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
- Receiving vasopressors
- All patients must be enrolled into the study within 72 hours of ICU admission
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.
- Medical subject headings
- Sepsis, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (3)
28 day mortality
The same sample of influenza patients will be used for mortality analysis. Based on published and unpublished data, 28-day mortality in critically-ill influenza patients admitted to ICUs ranges from 10-40%, even during non-pandemic periods. Based on these estimates, our sample size (n=75 younger and n=75 older) provides 84% power (two-sided alpha 0.05 comparison) to detect a difference in incidence of 29% and 9%, which is a conservative estimate of the difference between the younger and older groups.
Measured: 28 days
Interferon-induced transmembrane protein expression in platelets
Recent evidence also demonstrates that IFITM-3 acts as a membrane organizer by facilitating clathrin-mediated endocytosis (CME). This membrane-organizing process allows cells to internalize molecules and viruses. CME regulates platelet membrane organization. IFITM-3 is demonstrated as necessary for host defenses against influenza virus. Moreover, with absent or reduced levels of IFITM-3, cells do not effectively restrict viral replication, an impaired response that may influence adverse clinical outcomes.
Measured: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90
IFITM-3 mRNA
Platelet IFITM-3 protein levels have been seen to be increased in influenza patients and correlated with IFITM-3 mRNA (r2=0.33, p<0.005). However, in hospitalized influenza patients, platelet IFITM-3 mRNA and protein expression was decreased in older, compared to young patients.
It is hypothesized that influenza will induce expression of IFITM family members in platelets; IFITM's expression will be reduced in older compared to young influenza patients. This hypothesis will be tested to determine whether or not influenza induces IFITM-3 expression in human platelets and compare older and young subjects. Here, an outcome of IFITM-3 protein will be tracked in conjunction with mRNA.
Measured: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2017 (estimated)
- Study start21 Dec 2014
- Primary completionOct 2019 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Intermountain Health Care, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- University of Utah
- Responsible party
- Principal investigator, Samuel Brown, Intermountain Health Care, Inc.
- Investigators
- Samuel M Brown, MD MS, Principal investigator, Intermountain Health Care, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03010410
- Sponsor's protocol ID
- 1040298
- Status last verified
- Aug 2019
- First submitted
- 3 Jan 2017
- Last updated
- 13 Aug 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet Immune Responses in Aging and Influenza and Sepsis (INVACS)
- ClinicalTrials.gov ID
- NCT03010410
- Acronym / sponsor ID
- 1040298
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Intermountain Health Care, Inc.University, hospital or other
- Collaborators
- University of Utah
- Study start
- 21 Dec 2014 (actual)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 5 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This will be a prospective observational cohort study comparing older (age≥65) and younger (age<65) influenza and sepsis patients.
Key inclusion criteria (19 listed)
- ≥18 years old at the time of enrollment
- Meet one of the following three main criteria:
- 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.
- OR
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
90 day mortality
Time frame: 90 days
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.
3 secondary outcomes
28 day mortality
Time frame: 28 days
Interferon-induced transmembrane protein expression in platelets
Time frame: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90
IFITM-3 mRNA
Time frame: 24(±12) hours of diagnosis (day 0 or 1), day 3, 5, and 90.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Samuel M Brown, MD MS principal investigator
Intermountain Health Care, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Influenza, run by Intermountain Health Care, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
90 day mortality (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.