Sepsis Clinical Trial
— VAMp-sepsisOfficial title:
Validation of Molecular and Protein Biomarkers in Sepsis
Background:
Sepsis (blood poisoning) is a clinical syndrome characterised by a dysregulated host response
to infection causing life-threatening organ dysfunction which results in admission to an
intensive care unit. It typically shows an initial harmful inflammation resulting from the
immune system's overreaction to a severe infection. It is a major healthcare problem,
affecting millions of people worldwide. In the UK, it kills over 37,000 people/year, costing
the NHS £2.5 billion a year, and is increasing in incidence. Despite extensive efforts to
tackle this burden, at present, however, there are no specific and effective therapies for
this illness.
Sepsis is a potentially life-threatening condition caused by a severe infection. When someone
develops sepsis, inflammation occurs not just at the site of the infection but throughout the
whole body. This widespread inflammation can be very harmful. It is known that similar
responses occur in other conditions, not relating to infection.
The investigators are recruiting patients with severe infections causing organ failure (also
known as severe sepsis/ septicaemia and septic shock) and also patients where widespread
inflammation, not related to infection, causes organ failure. In this study the investigators
hope to find out whether certain groups of genetic and blood based protein markers of sepsis
can forewarn the clinicians to this condition and also highlight patients who are responding
well to the treatment.
Although it is known that the majority of the patients suffering from sepsis will survive
their ICU stay and leave the hospital alive, there is insufficient data how these patients do
on a longer term, i.e. after some time at home. To date there is little information on the
ability of the observed genetic and blood based protein markers to predict the functional
status of the patients surviving these conditions.
Status | Recruiting |
Enrollment | 270 |
Est. completion date | November 2021 |
Est. primary completion date | November 2021 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Inclusion Criteria for community-acquired Sepsis and Septic Shock 1. Age => 18 2. Admission to hospital within 72 hours of symptoms onset and development of clinical signs of sepsis 3. Diagnosis of sepsis - SEPSIS is defined as a (1) DEFINED FOCUS OF INFECTION AND (2) SOFA>2, with at least ONE organ specific SOFA subscore =2. 1. (1) DEFINED FOCUS OF INFECTION is indicated by either i. An organism grown in blood or sterile site OR ii. An abscess or infected tissue (e.g. pneumonia, peritonitis, urinary tract, vascular line infection, soft tissue, etc). 2. (2) The SOFA score criteria are described in the Appendix [7] - SEPTIC SHOCK is defined as SEPSIS plus the presence of hypotension requiring the use of vasopressors to maintain mean arterial pressure of 65 mmHg or greater and having a serum lactate level greater than 2 mmol/L persisting after adequate fluid resuscitation [8] Inclusion Criteria for Critically Ill patients without infection 1. Patients admitted to the ICU following out-of hospital cardiac arrest OR Patients admitted to the ICU following major trauma (ISS>12) OR Patients admitted to the ICU following pancreatitis 2. Have multiorgan failure as defined by SOFA>2, with at least ONE organ specific SOFA subscore =2. 3. Patients must not be receiving antibiotics for treatment of known or suspected infection 4. patient already has or will require arterial cannulation as part of standard treatment Exclusion Criteria: - 1. Patients who are on immune-modulating therapy (e.g., methotrexate, prednisolone >5mg/day, or other immunosuppressants) for any length of time within 6 months of index admission 2. Patients with acquired cellular immune deficiency (E.g. active HIV infection or AIDS); 3. Patients with concurrent blood-borne viral infections (E.g. Hepatitis B or C) 4. Patients with any haematological malignancy in their past medical history; 5. Patients who are on chronic haemodialysis; 6. Solid organ transplant recipients; 7. Patients who have biopsy, image or endoscopy proven liver cirrhosis; 8. Patients who are not expected to survive beyond 90 days due to the advancement of their underlying disease. |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Hampshire Hospitals NHS Foundation Trust | Basingstoke | |
United Kingdom | Public Health England | London | |
United Kingdom | Aneurin Bevan University Health Board | Newport | Gwent |
Lead Sponsor | Collaborator |
---|---|
Public Health England | Aneurin Bevan University Health Board, Cardiff University |
United Kingdom,
Cohen J, Vincent JL, Adhikari NK, Machado FR, Angus DC, Calandra T, Jaton K, Giulieri S, Delaloye J, Opal S, Tracey K, van der Poll T, Pelfrene E. Sepsis: a roadmap for future research. Lancet Infect Dis. 2015 May;15(5):581-614. doi: 10.1016/S1473-3099(15)70112-X. Epub 2015 Apr 19. Review. Erratum in: Lancet Infect Dis. 2015 Aug;15(8):875. — View Citation
Kempsell KE, Ball G, Szakmany T. Issues in biomarker identification, validation and development for disease diagnostics in Public Health. Expert Rev Mol Diagn. 2016;16(4):383-6. doi: 10.1586/14737159.2016.1133300. Epub 2016 Jan 22. — View Citation
Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority - A WHO Resolution. N Engl J Med. 2017 Aug 3;377(5):414-417. doi: 10.1056/NEJMp1707170. Epub 2017 Jun 28. — View Citation
Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, Angus DC, Rubenfeld GD, Singer M; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):775-87. doi: 10.1001/jama.2016.0289. Review. — View Citation
Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287. — View Citation
Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015 May 13;7(287):287ra71. doi: 10.1126/scitranslmed.aaa5993. — View Citation
Sweeney TE, Thomas NJ, Howrylak JA, Wong HR, Rogers AJ, Khatri P. Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust Diagnostic for Acute Respiratory Distress Syndrome. Crit Care Med. 2018 Feb;46(2):244-251. doi: 10.1097/CCM.0000000000002839. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | mRNA expression levels | mRNA expression levels from peripheral blood cells | Day 1 ICU/Hospital admission | |
Secondary | Mortality | All-cause mortality | 30 days | |
Secondary | Mortality | All-cause mortality | 90 days | |
Secondary | Health related quality of life | EuroQol Group 5 Domain questionnaire (EQ-5D). Range 1 to 5 in the domains. Higher values indicate worse health outcomes in the subdomains. | 6 months |
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