SepsisPliNOSa® TestNCT01371929
Plasma Inducible Nitric Oxide Synthase (iNOS) Assay and Sepsis Study
An observational study of Sepsis and Severe Sepsis, run by Research & Diagnostic Antibodies.
Trial summary
The primary objective is to demonstrate that the plasma inducible nitric oxide synthase (iNOS) assay (PliNOSa® test) has an acceptable relative risk ratio for predicting the onset of sepsis within 72 hours of testing when performed on the first day a patient is admitted or transferred to the intensive care unit (ICU)… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Severe Sepsis, Septic Shock
- How many people
- 166 participants
- Where
- No sites listed yet
- Study dates
- 4 Feb 2013to 30 Sep 2015
- 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: The study population will consist of 290 consecutively enrolled critically ill ICU patients who are considered to be at risk of becoming septic based upon their clinical presentation due to trauma, or a surgical procedure, or threatened or actual respiratory failure, or hemodynamic instability; and recruited from three clinical sites. The first 40 study subjects will comprise the pilot cohort and the remaining 250 study subjects will comprise the pivotal cohort.
Who may be able to join
- Male or female
- 18 years of age or older
- May be designated Do Not Attempt to Resuscitate / Do Not Intubate (DNAR / DNI) if they are committed to FULL CARE
- Study subject or their legal representative must have read, understood and provided written informed consent after the clinical study has been fully explained and their questions answered
- Subject must be admitted to or transferred to an Intensive Care Unit (ICU) and expected to require ICU-level of Care >24 hours for any of the following reasons:
- Following a surgical procedure
Show all 11Show fewer
- Following a traumatic injury
- For threatened or actual respiratory failure
- For hemodynamic instability
- Subject is considered to be at risk of developing sepsis during the next 72 hours based upon his/her clinical presentation
- Must have an in-dwelling line from which blood can be drawn.
Who cannot join
- Cannot be already septic, severely septic or in septic shock as defined by a recent positive culture (< 48 hrs) plus 2 or more of the signs and symptoms of sepsis listed in Table 1, "Diagnostic Criteria for Sepsis" in Levy MM, et al (2003) Crit Care Med, 31#4:1250-1256.
- Cannot be moribund (not expected to survive 48 hours)
- Cannot be expected to be discharged from the ICU in under 3 days
- Cannot be pregnant
- Cannot be a prisoner
About this study
Official title: Evaluation of the PliNOSa® Test as an Aid in the Risk Assessment for the Onset of Sepsis
The primary objective is to demonstrate that the plasma inducible nitric oxide synthase (iNOS) assay (PliNOSa® test) has an acceptable relative risk ratio for predicting the onset of sepsis within 72 hours of testing when performed on the first day a patient is admitted or transferred to the intensive care unit (ICU) and is considered to be at risk of becoming septic. The PliNOSa® test measures inducible nitric oxide synthase (iNOS) in plasma and uses a pre-determined iNOS cut-off value to identify patients at risk for the onset of the sepsis pathology.
Read the detailed description
At present, an accurate and definitive clinical test to predict early the onset of the sepsis pathology does not exist. At least 7 million people per year enter into the early stages of the sepsis pathology, which will lead to more than 250,000 deaths per year in the USA and more than 750,000 worldwide. An early, accurate, and reliable test that can assess an intensive care unit (ICU) patient's risk of becoming septic would be a major medical breakthrough. A large unmet clinical laboratory need exists for a test that can aid physicians in assessing their patient's risk for the onset of the sepsis pathology. The current culture procedures suffer from a number of problems. (1) They are slow. The first answer is obtained only after 24 hours of culture, and an absolute answer requires a minimum of 48 hours of culture. (2) Blood culture only yields positive results (i.e. sepsis is present) in approximately 28% of patients who become septic, thus over 70% of the patients do not yield positive blood cultures. Everyone in the sepsis field agrees that better IVD tests for the sepsis pathology are desperately needed. Our PliNOSa IVD test based upon the presence of iNOS in plasma should identify those patients as being at risk for developing sepsis since our assay is not dependent upon the culturing of live bacteria or other micro-organisms.
Sepsis develops from a variety of bacterial and fungal sources stemming from the patient's inability to fight infection, and is commonly acquired while recovering from severe injuries and surgery in hospitals. An early, accurate, and reliable clinical diagnostics test for the onset of sepsis currently does not exist, but an enormous clinical laboratory need does exist. In January 2008, Levenson reviewed the current status of the clinical diagnosis of sepsis and concluded [1] that none of the currently FDA cleared risk-assessment tests work well and [2] that new biomarkers specific for the sepsis pathology would be a major medical breakthrough. In 2000, the Institute of Medicine of the National Academy of Science estimated the cost to the US healthcare system to be $17 - 29 billion annually. The presence in plasma of a normally intracellular protein, inducible nitric oxide synthase (iNOS), has been found to be an early and accurate biomarker for the onset of the sepsis pathology. Data gathered using our in vitro diagnostic (IVD) test to analyze more than 1,200 blood samples collected during our clinical studies on 350 study subjects (295 ICU patients and 55 healthy volunteers) demonstrated that iNOS is present only in plasma samples obtained from people suffering from the onset of sepsis. In our three clinical studies, the latter two of which were partially funded by the NIH, our candidate IVD test for plasma iNOS was found to predict the onset of sepsis 24 - 72 hours before the appearance of the physiological symptoms of the pathology.
The superiority of plasma iNOS as compared to other potential biochemical markers of SIRS (pre-sepsis) and sepsis was assessed using the data from our third clinical study. Four cohorts from this study were analyzed for the plasma levels for four potential biomarkers of the sepsis pathology: iNOS, procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα). The four cohorts are (1) 36 normal healthy individuals as Group A; (2) critically injured patients who remained SIRS and septic negative throughout the entire study period as Group B; (3) critically ill patients who became septic during the study period, with their plasma levels 24 hours before the symptoms of sepsis were recognized by the attending doctors as Group C; and (4) confirmed septic patients who were enrolled in our study and had not received antibiotics prior to their enrollment as Group D. Only plasma iNOS was found to differentiate between non-septic critically ill patients (Group B) and the critically ill patients who were developing sepsis (Group C) or were already septic (Group D). The plasma level of procalcitonin, one of the FDA cleared IVD tests, was not specific for sepsis since a number of normal healthy volunteers and many of the non-SIRS and non-septic patients had elevated plasma levels of procalcitonin (PCT).
To summarize, infections in intensive care units and other hospital settings can be caused by different types of organisms, such as bacteria and fungi. These infections annually cause more than 7,000,000 cases of SIRS (pre-sepsis) that can deteriorate to sepsis, severe sepsis with organ dysfunction, and septic shock with multiple organ failure. To date, three clinical studies have been conducted on this project in which 295 ICU patients and 55 healthy volunteers have been enrolled and studied. The data obtained during these prior clinical studies clearly demonstrate that a measurable increase in the plasma level of iNOS occurs during the onset of the sepsis pathology. The main focus of this research proposal is to gather the data needed to obtain FDA clearance to market our new PliNOSa® test by demonstrating in a statistically significant number of critically ill ICU patients that the presence of iNOS in plasma is a reliable early biomarker as a risk assessment aid for the onset of sepsis.
- Conditions
- Sepsis, Severe Sepsis, Septic Shock
- Medical subject headings
- Sepsis, Shock, Septic
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 |
|---|---|---|
| ICU patients who become septic | Patients considered to be at risk of becoming septic based upon his/her clinical presentation during admittance or transfer to an ICU will be tested for the presence of plasma iNOS using our PliNOSa test on the day of ICU entry and their sepsis status will be followed for three days to determine if they develop sepsis, severe sepsis, or septic shock. Approximately, 50% of the enrolled patients are expected to develop sepsis, severe sepsis, or septic shock. | |
| ICU patients who do not become septic | Patients considered to be at risk of becoming septic based upon his/her clinical presentation during admittance or transfer to an ICU will be tested for the presence of plasma iNOS using our PliNOSa test on the day of ICU entry and their sepsis status will be followed for three days to determine if they develop sepsis, severe sepsis, or septic shock. Approximately, 50% of the enrolled patients are expected NOT to develop sepsis, severe sepsis, or septic shock. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of the PliNOSa test for a Positive Percent Agreement greater than 75% or a Negative Percent Agreement greater than 75% for predicting in ICU patients the onset of sepsis diagnosed within 72 hours of a plasma sample collected on study day 1.
A successful result (rejection of the null hypothesis) will be achieved if the Positive Percent Agreement is greater than 75% or the Negative Percent Agreement is greater than 75%.
Measured: First 72 hours after entry into the ICU
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2011 (estimated)
- Study start4 Feb 2013
- Primary completion30 Sep 2015
- Study completion30 Sep 2015
Why it stopped: NIH funding ended prior to full enrollment in the clinical study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 166 participants (actual)
Sponsor and investigators
- Lead sponsor
- Research & Diagnostic Antibodies
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Principal investigator, Dr. Robert Webber, Research & Diagnostic Antibodies
- Investigators
- Robert J Webber, Ph.D., Principal investigator, Research & Diagnostic Antibodies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01371929
- Sponsor's protocol ID
- RDAbs 11-001
- Other IDs
- 1RC3GM093717-01
- Acronym
- PliNOSa® Test
- Status last verified
- Nov 2023
- First submitted
- 8 Jun 2011
- Last updated
- 18 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Webber RJ, Sweet RM, Webber DS. Inducible Nitric Oxide Synthase in Circulating Microvesicles: Discovery, Evolution, and Evidence as a Novel Biomarker and the Probable Causative Agent for Sepsis. J Appl Lab Med. 2019 Jan;3(4):698-711. doi: 10.1373/jalm.2018.026377.
PubMed 30937423Webber RJ, Rodriguez JG, Webber DS, Dunnebacke TH. Development, characterization, and epitope mapping of a panel of twenty-four monoclonal antibodies specific for human inducible nitric oxide synthase. Hybridoma (Larchmt). 2005 Feb;24(1):6-13. doi: 10.1089/hyb.2005.24.6.
PubMed 15785204Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL Jr, Platt R; Academic Medical Center Consortium Sepsis Project Working Group. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997 Jul 16;278(3):234-40.
PubMed 9218672Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. doi: 10.1056/NEJMoa022139.
PubMed 12700374Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.
PubMed 12682500Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):762-74. doi: 10.1001/jama.2016.0288.
PubMed 26903335Gambim MH, do Carmo Ade O, Marti L, Verissimo-Filho S, Lopes LR, Janiszewski M. Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care. 2007;11(5):R107. doi: 10.1186/cc6133.
PubMed 17894858Azevedo LC, Janiszewski M, Pontieri V, Pedro Mde A, Bassi E, Tucci PJ, Laurindo FR. Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit Care. 2007;11(6):R120. doi: 10.1186/cc6176.
PubMed 17996049Mortaza S, Martinez MC, Baron-Menguy C, Burban M, de la Bourdonnaye M, Fizanne L, Pierrot M, Cales P, Henrion D, Andriantsitohaina R, Mercat A, Asfar P, Meziani F. Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats. Crit Care Med. 2009 Jun;37(6):2045-50. doi: 10.1097/CCM.0b013e3181a00629.
PubMed 19384196Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014 Apr;20(4):195-203. doi: 10.1016/j.molmed.2014.01.007. Epub 2014 Feb 24.
PubMed 24581450Tse MT. Trial watch: Sepsis study failure highlights need for trial design rethink. Nat Rev Drug Discov. 2013 May;12(5):334. doi: 10.1038/nrd4016. No abstract available.
PubMed 23629495
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the PliNOSa® Test as an Aid in the Risk Assessment for the Onset of Sepsis
- ClinicalTrials.gov ID
- NCT01371929
- Acronym / sponsor ID
- PliNOSa® Test / RDAbs 11-001
- Conditions
- Sepsis, Severe Sepsis, Septic Shock
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: NIH funding ended prior to full enrollment in the clinical study
- Enrolment
- 166 participants (actual)
- Lead sponsor
- Research & Diagnostic AntibodiesIndustry (pharma, biotech, devices)
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- 4 Feb 2013 (actual)
- Primary completion
- 30 Sep 2015 (actual)
- Study completion
- 30 Sep 2015 (actual)
- First posted
- 13 Jun 2011 (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.
The primary objective is to demonstrate that the plasma inducible nitric oxide synthase (iNOS) assay (PliNOSa® test) has an acceptable relative risk ratio for predicting the onset of sepsis within 72 hours of testing when performed on the first day a patient is admitted or transferred to the intensive care unit (ICU) and is considered to be at risk of becoming septic. The PliNOSa® test measures inducible nitric oxide synthase (iNOS) in plasma and uses a pre-determined iNOS cut-off value to identify patients at risk for the onset of the sepsis pathology.
Detailed description
At present, an accurate and definitive clinical test to predict early the onset of the sepsis pathology does not exist. At least 7 million people per year enter into the early stages of the sepsis pathology, which will lead to more than 250,000 deaths per year in the USA and more than 750,000 worldwide. An early, accurate, and reliable test that can assess an intensive care unit (ICU) patient's risk of becoming septic would be a major medical breakthrough. A large unmet clinical laboratory need exists for a test that can aid physicians in assessing their patient's risk for the onset of the sepsis pathology. The current culture procedures suffer from a number of problems. (1) They are slow. The first answer is obtained only after 24 hours of culture, and an absolute answer requires a minimum of 48 hours of culture. (2) Blood culture only yields positive results (i.e. sepsis is present) in approximately 28% of patients who become septic, thus over 70% of the patients do not yield positive blood cultures. Everyone in the sepsis field agrees that better IVD tests for the sepsis pathology are desperately needed. Our PliNOSa IVD test based upon the presence of iNOS in plasma should identify those patients as being at risk for developing sepsis since our assay is not dependent upon the culturing of live bacteria or other micro-organisms.
Sepsis develops from a variety of bacterial and fungal sources stemming from the patient's inability to fight infection, and is commonly acquired while recovering from severe injuries and surgery in hospitals. An early, accurate, and reliable clinical diagnostics test for the onset of sepsis currently does not exist, but an enormous clinical laboratory need does exist. In January 2008, Levenson reviewed the current status of the clinical diagnosis of sepsis and concluded [1] that none of the currently FDA cleared risk-assessment tests work well and [2] that new biomarkers specific for the sepsis pathology would be a major medical breakthrough. In 2000, the Institute of Medicine of the National Academy of Science estimated the cost to the US healthcare system to be $17 - 29 billion annually. The presence in plasma of a normally intracellular protein, inducible nitric oxide synthase (iNOS), has been found to be an early and accurate biomarker for the onset of the sepsis pathology. Data gathered using our in vitro diagnostic (IVD) test to analyze more than 1,200 blood samples collected during our clinical studies on 350 study subjects (295 ICU patients and 55 healthy volunteers) demonstrated that iNOS is present only in plasma samples obtained from people suffering from the onset of sepsis. In our three clinical studies, the latter two of which were partially funded by the NIH, our candidate IVD test for plasma iNOS was found to predict the onset of sepsis 24 - 72 hours before the appearance of the physiological symptoms of the pathology.
The superiority of plasma iNOS as compared to other potential biochemical markers of SIRS (pre-sepsis) and sepsis was assessed using the data from our third clinical study. Four cohorts from this study were analyzed for the plasma levels for four potential biomarkers of the sepsis pathology: iNOS, procalcitonin (PCT), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNFα). The four cohorts are (1) 36 normal healthy individuals as Group A; (2) critically injured patients who remained SIRS and septic negative throughout the entire study period as Group B; (3) critically ill patients who became septic during the study period, with their plasma levels 24 hours before the symptoms of sepsis were recognized by the attending doctors as Group C; and (4) confirmed septic patients who were enrolled in our study and had not received antibiotics prior to their enrollment as Group D. Only plasma iNOS was found to differentiate between non-septic critically ill patients (Group B) and the critically ill patients who were developing sepsis (Group C) or were already septic (Group D). The plasma level of procalcitonin, one of the FDA cleared IVD tests, was not specific for sepsis since a number of normal healthy volunteers and many of the non-SIRS and non-septic patients had elevated plasma levels of procalcitonin (PCT).
To summarize, infections in intensive care units and other hospital settings can be caused by different types of organisms, such as bacteria and fungi. These infections annually cause more than 7,000,000 cases of SIRS (pre-sepsis) that can deteriorate to sepsis, severe sepsis with organ dysfunction, and septic shock with multiple organ failure. To date, three clinical studies have been conducted on this project in which 295 ICU patients and 55 healthy volunteers have been enrolled and studied. The data obtained during these prior clinical studies clearly demonstrate that a measurable increase in the plasma level of iNOS occurs during the onset of the sepsis pathology. The main focus of this research proposal is to gather the data needed to obtain FDA clearance to market our new PliNOSa® test by demonstrating in a statistically significant number of critically ill ICU patients that the presence of iNOS in plasma is a reliable early biomarker as a risk assessment aid for the onset of sepsis.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICU patients who become septic | – | –Patients considered to be at risk of becoming septic based upon his/her clinical presentation during admittance or transfer to an ICU will be tested for the presence of plasma iNOS using our PliNOSa test on the day of ICU entry and their sepsis status will be followed for three days to determine if they develop sepsis, severe sepsis, or septic shock. Approximately, 50% of the enrolled patients are expected to develop sepsis, severe sepsis, or septic shock. |
| ICU patients who do not become septic | – | –Patients considered to be at risk of becoming septic based upon his/her clinical presentation during admittance or transfer to an ICU will be tested for the presence of plasma iNOS using our PliNOSa test on the day of ICU entry and their sepsis status will be followed for three days to determine if they develop sepsis, severe sepsis, or septic shock. Approximately, 50% of the enrolled patients are expected NOT to develop sepsis, severe sepsis, or septic shock. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population will consist of 290 consecutively enrolled critically ill ICU patients who are considered to be at risk of becoming septic based upon their clinical presentation due to trauma, or a surgical procedure, or threatened or actual respiratory failure, or hemodynamic instability; and recruited from three clinical sites. The first 40 study subjects will comprise the pilot cohort and the remaining 250 study subjects will comprise the pivotal cohort.
Key inclusion criteria (11 listed)
- Male or female
- 18 years of age or older
- May be designated Do Not Attempt to Resuscitate / Do Not Intubate (DNAR / DNI) if they are committed to FULL CARE
- Study subject or their legal representative must have read, understood and provided written informed consent after the clinical study has been fully explained and their questions answered
- Subject must be admitted to or transferred to an Intensive Care Unit (ICU) and expected to require ICU-level of Care >24 hours for any of the following reasons:
Key exclusion criteria (5 listed)
- Cannot be already septic, severely septic or in septic shock as defined by a recent positive culture (< 48 hrs) plus 2 or more of the signs and symptoms of sepsis listed in Table 1, "Diagnostic Criteria for Sepsis" in Levy MM, et al (2003) Crit Care Med, 31#4:1250-1256.
- Cannot be moribund (not expected to survive 48 hours)
- Cannot be expected to be discharged from the ICU in under 3 days
- Cannot be pregnant
- Cannot be a prisoner
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
Evaluation of the PliNOSa test for a Positive Percent Agreement greater than 75% or a Negative Percent Agreement greater than 75% for predicting in ICU patients the onset of sepsis diagnosed within 72 hours of a plasma sample collected on study day 1.
Time frame: First 72 hours after entry into the ICU
A successful result (rejection of the null hypothesis) will be achieved if the Positive Percent Agreement is greater than 75% or the Negative Percent Agreement is greater than 75%.
Results and safety
The study was stopped early (reason given: NIH funding ended prior to full enrollment in the clinical study). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Background: PubMed 30937423Webber RJ, Sweet RM, Webber DS. Inducible Nitric Oxide Synthase in Circulating Microvesicles: Discovery, Evolution, and Evidence as a Novel Biomarker and the Probable Causative Agent for Sepsis. J Appl Lab Med. 2019 Jan;3(4):698-711. doi: 10.1373/jalm.2018.026377.
- Background: PubMed 15785204Webber RJ, Rodriguez JG, Webber DS, Dunnebacke TH. Development, characterization, and epitope mapping of a panel of twenty-four monoclonal antibodies specific for human inducible nitric oxide synthase. Hybridoma (Larchmt). 2005 Feb;24(1):6-13. doi: 10.1089/hyb.2005.24.6.
- Background: PubMed 9218672Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, Black E, Schwartz JS, Moore R, Johnson BL Jr, Platt R; Academic Medical Center Consortium Sepsis Project Working Group. Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA. 1997 Jul 16;278(3):234-40.
- Background: PubMed 12700374Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003 Apr 17;348(16):1546-54. doi: 10.1056/NEJMoa022139.
- Background: PubMed 12682500Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G; SCCM/ESICM/ACCP/ATS/SIS. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003 Apr;31(4):1250-6. doi: 10.1097/01.CCM.0000050454.01978.3B.
- Background: PubMed 26903335Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, Rubenfeld G, Kahn JM, Shankar-Hari M, Singer M, Deutschman CS, Escobar GJ, Angus DC. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):762-74. doi: 10.1001/jama.2016.0288.
- Background: PubMed 17894858Gambim MH, do Carmo Ade O, Marti L, Verissimo-Filho S, Lopes LR, Janiszewski M. Platelet-derived exosomes induce endothelial cell apoptosis through peroxynitrite generation: experimental evidence for a novel mechanism of septic vascular dysfunction. Crit Care. 2007;11(5):R107. doi: 10.1186/cc6133.
- Background: PubMed 17996049Azevedo LC, Janiszewski M, Pontieri V, Pedro Mde A, Bassi E, Tucci PJ, Laurindo FR. Platelet-derived exosomes from septic shock patients induce myocardial dysfunction. Crit Care. 2007;11(6):R120. doi: 10.1186/cc6176.
- Background: PubMed 19384196Mortaza S, Martinez MC, Baron-Menguy C, Burban M, de la Bourdonnaye M, Fizanne L, Pierrot M, Cales P, Henrion D, Andriantsitohaina R, Mercat A, Asfar P, Meziani F. Detrimental hemodynamic and inflammatory effects of microparticles originating from septic rats. Crit Care Med. 2009 Jun;37(6):2045-50. doi: 10.1097/CCM.0b013e3181a00629.
- Background: PubMed 24581450Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med. 2014 Apr;20(4):195-203. doi: 10.1016/j.molmed.2014.01.007. Epub 2014 Feb 24.
- Background: PubMed 23629495Tse MT. Trial watch: Sepsis study failure highlights need for trial design rethink. Nat Rev Drug Discov. 2013 May;12(5):334. doi: 10.1038/nrd4016. No abstract available.
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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.
Robert J Webber, Ph.D. principal investigator
Research & Diagnostic Antibodies
Questions about this trial
What is this clinical trial studying?
An observational study of Sepsis and Severe Sepsis, run by Research & Diagnostic Antibodies.
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 11 inclusion and 5 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: stopped early, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was stopped early (reason given: NIH funding ended prior to full enrollment in the clinical 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?
Evaluation of the PliNOSa test for a Positive Percent Agreement greater than 75% or a Negative Percent Agreement greater than 75% for predicting in ICU patients the onset of sepsis diagnosed within 72 hours of a plasma sample collected on study day 1. (time frame: First 72 hours after entry into the ICU). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01371929, which also lists 11 linked publications.
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 18 Nov 2023.