Plasma Inducible Nitric Oxide Synthase (iNOS) Assay and Sepsis Study

NCT01371929 | Terminated DMC

• 2 other identifiers: RDAbs 11-0011RC3GM093717-01
• Study Type: observational
• Target: 166
• Locations: 0 countries
• Sites: N/A

Brief 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) 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.

Conditions

Sepsis; Severe Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (1)

• 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%.

  First 72 hours after entry into the ICU

Study Arms (2)

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.

Eligibility Criteria

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

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.

You may qualify if:

• Male or female
• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Research & Diagnostic Antibodies: lead
• National Institute of General Medical Sciences (NIGMS): collaborator

Related Publications (11)

• 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.

  PMID: 30937423 BACKGROUND

• Webber 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.

  PMID: 15785204 BACKGROUND

• Sands 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.

  PMID: 9218672 BACKGROUND

• Martin 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.

  PMID: 12700374 BACKGROUND

• Levy 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.

  PMID: 12682500 BACKGROUND

• Seymour 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.

  PMID: 26903335 BACKGROUND

• Gambim 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.

  PMID: 17894858 BACKGROUND

• Azevedo 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.

  PMID: 17996049 BACKGROUND

• Mortaza 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.

  PMID: 19384196 BACKGROUND

• Marshall 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.

  PMID: 24581450 BACKGROUND

• Tse 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.

  PMID: 23629495 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

heparinized plasma samples

MeSH Terms

Conditions

Sepsis; Shock, Septic

Condition Hierarchy (Ancestors)

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

Study Officials

• Robert J Webber, Ph.D.

  Research & Diagnostic Antibodies

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President

Study Record Dates

• First Submitted: June 8, 2011
• First Posted: June 13, 2011
• Study Start: February 4, 2013
• Primary Completion: September 30, 2015
• Study Completion: September 30, 2015
• Last Updated: November 18, 2023

Record last verified: 2023-11