Sepsis
Conditions
Brief summary
Carbon-12 and carbon-13 are naturally-abundant isotopes in exhaled breath carbon dioxide. The ratio of carbon-13 to carbon-12 in exhaled breath is known as the breath delta value (BDV). This study is seeking to determine if the breath delta value of critically ill adults is an early indicator of the onset of infection that may lead to sepsis.
Detailed description
Sepsis is a major complication for any patient, and its management is an acknowledged challenge for intensivists. Sepsis has unpredictable onset and progression, and is a leading cause of death in ICUs with a mortality rate of 30-50%. Annually in the US, 1.4M cases involve hospitalization, 750,000 cases of severe sepsis or septic shock, and \ 260,000 cases of sepsis related death have been reported in recent years. Current experience of UF Health investigators in surgical ICUs is 1 -2 sepsis, severe sepsis, or septic shock patients per day, of which \ 10% are trauma patients. Of trauma patients, \ 8% develop sepsis during their ICU stay. Breath delta value is hypothesized to be a biomarker of infection. Breath delta value is not a defined clinical outcome related to human health, because this study is seeking to establish breath delta value as a biomarker of infection. This study is measuring the feasibility of the Isomark Canary™ device. If the Canary does not detect a significant decrease in breath delta value in those subjects who subsequently get an infection, it will not be feasible to use it for this purpose. Breath delta value will be collected to determine its relationship to infection, no health outcomes are being measured. This study is designed to determine if the BDV of adult ICU patients is an early indicator of the onset of infection that may lead to sepsis. The objectives of this study are: (1) to measure variation of BDV with time in adult ICU patients who agree to participate as research subjects; (2) to determine the magnitude of change of BDV in subjects who are subsequently diagnosed with severe infection and sepsis; (3) to define variation of BDV in adult trauma subjects who do not develop severe infection.
Interventions
DEVICEIsomark Canary™
Isomark, LLC is a Madison, Wisconsin-based company that has developed an investigational device, the Isomark Canary™, that is intended to determine the breath delta value of breath samples collected from critically ill patients.
Sponsors
University of Florida
Ohio State University
Washington University School of Medicine
University of Colorado, Denver
Isomark, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. age 18 years or older 2. critically ill patient admitted to trauma or surgical ICU 3. expected duration of hospital stay at least 120 hours (five days) from time of study enrollment 4. subject/LAR speaks a language of which the IRB has approved a consent form
Exclusion criteria
1. known infection at the time of enrollment per infection definitions in section 6.2 2. known use of systemic antibiotic, antimicrobial and/or antifungal therapy within the last 7 days (See Antibiotic Use section below) 3. prolonged antibiotic or antimicrobial use during the perioperative period (See Antibiotic Use section below) 4. currently active cancer, or receiving treatment for cancer (including but not limited to: radiation, chemotherapy, systemic orals, etc) 5. receiving high frequency ventilatory support 6. if not intubated, unable to cooperate with providing a breath sample 7. expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family/medical team (e.g., likely to withdraw life support measures within 24 hrs of screening) 8. female who is pregnant or lactating (negative serum or urine pregnancy test results within 48 hours of enrollment or to be performed during screening) 9. prisoner 10. known participation in an interventional research study within 30 days prior to enrollment (note: to be eligible, any interventional treatment must have ended at least 30 days ago) 11. Individuals who are directly affiliated with sponsor or study staff, or their immediate families. Immediate family is defined as spouse, domestic partner, parent, child, or sibling whether legally adopted or biological. 12. Any patient that is deemed unfit for study participation, per the Investigator's discretion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Breath Delta Value | Baseline to ICU discharge or 7 days, whichever came first | The variation in breath delta value was assessed regardless of infection status. Exhaled breath samples were collected from participants upon enrollment and every four hours thereafter until the end of the subject's study duration per protocol. Each subject was used as its own control for the purpose of trend analysis.The first breath sample collected was considered an individual's baseline sample. The change in the breath delta value was calculated from this baseline sample. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Infection Diagnosis | Days 1 through 7 | Daily analysis infection status from blood samples given from each participant. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Predictive Value of BDV for Infection Diagnosis | 7 days | Based on an ROC analysis the optimal cutoff value for indicating the presence of infection using the BDV is 1.4‰. Based on this cutoff value the sensitivity and specificity were calculated. Sensitivity, or the true positive rate, is the proportion of actual positives that are correctly identified. In this case, the sensitivity is the percentage of people who have an infection and were identified by the Isomark Canary as having an 'infection'. The specificity, or the true negative rate, is the promotion of actual negatives that are correctly identified as negative. In this case, the specificity is the proportion of people without infections that were correctly classified by the Isomark Canary as having 'no infection'. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Critically Ill Subjects at Risk for Infection Critically ill adult ICU subjects who are not suspected of having an infection at the time of ICU admission were enrolled as study subjects. | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Discharged in less than 5 days | 5 |
| Overall Study | Incorrectly place ventilator adaptor | 1 |
| Overall Study | Met exclusion criteria | 3 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Unable to provide breath sample | 1 |
Baseline characteristics
| Characteristic | Critically Ill Subjects at Risk for Infection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Change in Breath Delta Value
The variation in breath delta value was assessed regardless of infection status. Exhaled breath samples were collected from participants upon enrollment and every four hours thereafter until the end of the subject's study duration per protocol. Each subject was used as its own control for the purpose of trend analysis.The first breath sample collected was considered an individual's baseline sample. The change in the breath delta value was calculated from this baseline sample.
Time frame: Baseline to ICU discharge or 7 days, whichever came first
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Exhaled Breath | Change in Breath Delta Value | 0.44 parts per mil (‰) | Standard Error 1.09 |
Secondary
Number of Participants With an Infection Diagnosis
Daily analysis infection status from blood samples given from each participant.
Time frame: Days 1 through 7
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exhaled Breath | Number of Participants With an Infection Diagnosis | 11 Participants |
Other Pre-specified
Positive and Negative Predictive Value of BDV for Infection Diagnosis
Based on an ROC analysis the optimal cutoff value for indicating the presence of infection using the BDV is 1.4‰. Based on this cutoff value the sensitivity and specificity were calculated. Sensitivity, or the true positive rate, is the proportion of actual positives that are correctly identified. In this case, the sensitivity is the percentage of people who have an infection and were identified by the Isomark Canary as having an 'infection'. The specificity, or the true negative rate, is the promotion of actual negatives that are correctly identified as negative. In this case, the specificity is the proportion of people without infections that were correctly classified by the Isomark Canary as having 'no infection'.
Time frame: 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Exhaled Breath | Positive and Negative Predictive Value of BDV for Infection Diagnosis | 90.1 percent |
| Specificity | Positive and Negative Predictive Value of BDV for Infection Diagnosis | 66.7 percent |