Sepsis Clinical Trial
Official title:
Plasma Protein Biomarker Based Diagnostics of Outcome in Sepsis & CAP
We propose to develop novel diagnostic tests for severe sepsis and community acquired
pneumonia (CAP). This program, entitled Community Acquired Pneumonia & Sepsis Outcome
Diagnostics (CAPSOD), is a multidisciplinary collaboration involving investigators at six
organizations: NCGR; Duke University Medical Center, Durham, NC; Henry Ford Hospital,
Detroit, MI; Eli Lilly and Company, Indianapolis, IN; Indiana Centers for Applied Protein
Sciences, Indianapolis, IN; and ProSanos Corp., La Jolla, CA.
In the United States, Community Acquired Pneumonia is the sixth leading cause of death and
the number one cause of death from infectious diseases. Of the 5.6 million annual cases of
CAP, 1.1 million require hospitalization for intensive therapy. Sepsis, commonly known as
blood poisoning or bloodstream infection, is the tenth leading cause of death in the US and
the number one cause of death in non-cardiac intensive care units. Incidence of sepsis is
increasing by 9% each year and mortality rates vary between 25 and 50%. Cost to the US
healthcare system exceeds $20 billion each year.
In patients with suspected sepsis or early CAP, rapid identification of patients who will
develop severe sepsis or CAP is critical for effective management and positive outcome. The
CAPSOD study is designed to identify novel tests for early diagnosis of severe sepsis and
CAP. When performed in patients at the earliest stages of disease, these tests will have
prognostic value, rapidly identifying those who will have poor outcomes or complicated
courses.
CAPSOD will prospectively enroll patients with sepsis and CAP at Duke University Medical
Center and Henry Ford Hospital. The study will use advanced bioinformatic, metabolomic,
proteomic and mRNA sequencing technologies to identify specific protein changes, or
biomarkers, in patient blood samples that predict outcome in sepsis and CAP. Development of
biomarker-based tests will permit patient selection for appropriate disposition, such as the
intensive care unit, and use of intensive medical therapies, thereby reducing mortality and
increasing effectiveness of resource allocation.
Status | Recruiting |
Enrollment | 1200 |
Est. completion date | July 2010 |
Est. primary completion date | July 2010 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 6 Years and older |
Eligibility |
Inclusion Criteria: 1. Patient has known or acute infection or suspected infection AND patient must meet at least 2 of the following 4 criteria to be enrolled 1. A core temperature of >= 38°C (100.4°F) or <= 36°C (96.8°F) 2. Patients > 18 years of age, Heart rate of >= 90 beats/min Patients 13-18 years of age, Heart rate of >= 110 beats/min Patients 6-12 years of age, Heart rate of >= 130 beats/min 3. Patients > 18 years of age, Respiratory rate of >= 20 breaths/min Patients 13-18 years of age, Respiratory rate of >= 14 breaths/min Patients 6-12 years of age, Respiratory rate of >= 18 breaths/min OR PaCO2 of <= 32 mm Hg OR Use of Mechanical Ventilation for an acute respiratory process 4. Patients > 18 years of age, White cell count >= 12,000/mm3 or <= 4,000/mm3 Patients 13-18 years of age, White cell count >= 11,000/mm3 or <= 4,500/mm3 Patients 6-12 years of age, White cell count >= 13,500/mm3 or <= 4,500/mm3 OR A differential count showing > 10% immature neutrophils Exclusion Criteria: 1. Patient is less than 6 years of age. 2. Patient is not expected to survive 28 days because of uncorrectable medical condition (apart from pneumonia or sepsis), such as poorly controlled neoplasm or other end-stage disease, or patient has active DNR order 3. Human immunodeficiency virus (HIV) infection with a last known CD4 count of <50 mm3 4. Acute presence of a cerebral vascular event, active gastrointestinal hemorrhage, seizure (acute episode), drug overdose, burn injury, trauma 5. Patient is pregnant |
Observational Model: Cohort, Time Perspective: Prospective
Country | Name | City | State |
---|---|---|---|
United States | Henry Ford Hospital | Detroit | Michigan |
United States | Duke University Medical Center | Durham | North Carolina |
United States | Durham VA Medical Center | Durham | North Carolina |
Lead Sponsor | Collaborator |
---|---|
National Center for Genome Resources | Duke University, Durham VA Medical Center, Henry Ford Hospital, Hoffmann-La Roche, National Institute of Allergy and Infectious Diseases (NIAID), Pfizer |
United States,
Heuer JG, Cummins DJ, Edmonds BT. Multiplex proteomic approaches to sepsis research: case studies employing new technologies. Expert Rev Proteomics. 2005 Oct;2(5):669-80. Review. — View Citation
Heuer JG, Sharma GR, Gerlitz B, Zhang T, Bailey DL, Ding C, Berg DT, Perkins D, Stephens EJ, Holmes KC, Grubbs RL, Fynboe KA, Chen YF, Grinnell B, Jakubowski JA. Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis. Crit Care Med. 2004 Jul;32(7):1570-8. — View Citation
Kader HA, Tchernev VT, Satyaraj E, Lejnine S, Kotler G, Kingsmore SF, Patel DD. Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn's disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol. 2005 Feb;100(2):414-23. — View Citation
Kaukola T, Satyaraj E, Patel DD, Tchernev VT, Grimwade BG, Kingsmore SF, Koskela P, Tammela O, Vainionpää L, Pihko H, Aärimaa T, Hallman M. Cerebral palsy is characterized by protein mediators in cord serum. Ann Neurol. 2004 Feb;55(2):186-94. — View Citation
Kingsmore SF, Patel DD. Multiplexed protein profiling on antibody-based microarrays by rolling circle amplification. Curr Opin Biotechnol. 2003 Feb;14(1):74-81. Review. — View Citation
O'Brien LA, Gupta A, Grinnell BW. Activated protein C and sepsis. Front Biosci. 2006 Jan 1;11:676-98. Review. — View Citation
Perlee L, Christiansen J, Dondero R, Grimwade B, Lejnine S, Mullenix M, Shao W, Sorette M, Tchernev V, Patel D, Kingsmore S. Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics. Proteome Sci. 2004 Dec 15;2(1):9. — View Citation
Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. — View Citation
Rivers EP, McIntyre L, Morro DC, Rivers KK. Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ. 2005 Oct 25;173(9):1054-65. Review. — View Citation
Rivers EP, Nguyen HB, Huang DT, Donnino M. Early goal-directed therapy. Crit Care Med. 2004 Jan;32(1):314-5; author reply 315. — View Citation
Schweitzer B, Roberts S, Grimwade B, Shao W, Wang M, Fu Q, Shu Q, Laroche I, Zhou Z, Tchernev VT, Christiansen J, Velleca M, Kingsmore SF. Multiplexed protein profiling on microarrays by rolling-circle amplification. Nat Biotechnol. 2002 Apr;20(4):359-65. — View Citation
* Note: There are 11 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Death | Day 3 | No | |
Primary | Septic Shock | Day 3 | No | |
Primary | Severe Sepsis | Day 3 | No | |
Secondary | Time to death | 28 days | No | |
Secondary | Death | Day 5 | No | |
Secondary | Death | Day 7 | No | |
Secondary | Death | Day 28 | No | |
Secondary | Time to severe sepsis | 28 days | No | |
Secondary | Severe sepsis | Day 5 | No | |
Secondary | Severe sepsis | Day 7 | No | |
Secondary | Severe sepsis | Day 28 | No | |
Secondary | Time to septic shock | 28 days | No | |
Secondary | Septic Shock | Day 5 | No | |
Secondary | Septic Shock | Day 7 | No | |
Secondary | Septic shock | Day 28 | No | |
Secondary | Cryptic shock (ScvO2<65 or Lactate >2.5 and MAP >65 mmHg [>18 years of age] or SBP >90 [<18 years of age]) | Day 3 | No | |
Secondary | Time to Cryptic shock (ScvO2<65 or Lactate >2.5 and MAP >65 mmHg [>18 years of age] or SBP >90 [<18 years of age]) | Day 28 | No | |
Secondary | Cryptic shock (ScvO2<65 or Lactate >2.5 and MAP >65 mmHg [>18 years of age] or SBP >90 [<18 years of age]) | Day 5 | No | |
Secondary | Cryptic shock (ScvO2<65 or Lactate >2.5 and MAP >65 mmHg [>18 years of age] or SBP >90 [<18 years of age]) | Day 7 | No | |
Secondary | Cryptic shock (ScvO2<65 or Lactate >2.5 and MAP >65 mmHg [>18 years of age] or SBP >90 [<18 years of age]) | Day 28 | No | |
Secondary | Hospitalization | 24 hours | No | |
Secondary | Length of hospital stay | Days | No | |
Secondary | ICU admission | 28 days | No | |
Secondary | Length of ICU admission | Days | No | |
Secondary | Disposition | 28 day | No | |
Secondary | Renal dysfunction | 28 days | No | |
Secondary | Respiratory dysfunction | 28 days | No | |
Secondary | Hematology dysfunction | 28 days | No | |
Secondary | Metabolic dysfunction | 28 days | No | |
Secondary | Renal SOFA score | 28 days | No | |
Secondary | Lung SOFA score | 28 days | No | |
Secondary | Coagulation SOFA score | 28 days | No | |
Secondary | Liver SOFA score | 28 days | No | |
Secondary | CVS SOFA score | 28 dadys | No | |
Secondary | Time to respiratory SOFA Score | 28 days | No | |
Secondary | Time to coagulation SOFA score | 28 days | No | |
Secondary | Time to liver SOFA score | 28 days | No | |
Secondary | Time to CVS SOFA score | 28 days | No | |
Secondary | Time to Renal SOFA score | 28 days | No | |
Secondary | DIC score >5 (modified ISTH scoring system) | 28 days | No | |
Secondary | Time to DIC score > 5 | Days | No | |
Secondary | Development of ALI | 28 days | Yes | |
Secondary | Development of ARDS | 28 days | No | |
Secondary | Time to ALI | Days | No | |
Secondary | Time to ARDS | Days | No | |
Secondary | Ventilator | 28 days | No | |
Secondary | Ventilator days | Days | No | |
Secondary | MELD score | 28 days | No | |
Secondary | Effect of early goal directed therapy on primary and secondary end-points | 28 days | No | |
Secondary | Effect of Activated Protein C on primary and secondary end-points | 28 days | No | |
Secondary | Effect of stress-dose corticosteroids on primary and secondary end-points | 28 days | No | |
Secondary | Effect of intensive glycemic control on primary and secondary end-points | 28 days | No | |
Secondary | APACHE II score | enrollment | No | |
Secondary | APACHE II score | 24 hours | No | |
Secondary | PRISM III score | enrollment | No | |
Secondary | PRISM III score | 24 hours | No | |
Secondary | SOFA score | enrollment | No | |
Secondary | SOFA score | 24 hours | No | |
Secondary | CAP mortality | Day 3 | No | |
Secondary | CAP and severe sepsis | Day 3 | No | |
Secondary | CAP and septic shock | Day 3 | No | |
Secondary | Severe CAP (ATS criteria) | Day 3 | No | |
Secondary | Severe CAP (BTS criteria) | Day 3 | No | |
Secondary | Pneumococcal sepsis | Day 7 | No | |
Secondary | Staphylococcus aureus sepsis | Day 7 | No | |
Secondary | Gram negative rod sepsis | Day 7 | No | |
Secondary | Fungal sepsis | Day 7 | No | |
Secondary | SeptiFast result | Enrollment | No | |
Secondary | SeptiFast result | 24 hours | No | |
Secondary | Microbiologic culture result | Day 28 | No | |
Secondary | Urinary legionella antigen | 7 days | No | |
Secondary | Microbiologic culture | 7 days | No | |
Secondary | CAP, time to death | days | No | |
Secondary | CAP, mortality | Day 5 | No | |
Secondary | CAP, mortality | Day 7 | No | |
Secondary | CAP, mortality | Day 28 | No | |
Secondary | CAP, time to severe sepsis | Days | No | |
Secondary | CAP, severe sepsis | Day 5 | No | |
Secondary | CAP, severe sepsis | Day 7 | No | |
Secondary | CAP, severe sepsis | Day 28 | No | |
Secondary | CAP, time to septic shock | days | No | |
Secondary | CAP, septic shock | Day 5 | No | |
Secondary | CAP, septic shock | Day 7 | No | |
Secondary | CAP, septic shock | Day 28 | No | |
Secondary | Time to severe CAP (ATS and BTS criteria) | Days | No | |
Secondary | Severe CAP (ATS and BTS criteria) | Day 5 | No | |
Secondary | Severe CAP (ATS and BTS criteria) | Day 7 | No | |
Secondary | Severe CAP (ATS and BTS criteria) | Day 28 | No | |
Secondary | CAP, mechanical ventilation | 28 days | No | |
Secondary | CAP, time to mechanical ventilation | Days | No | |
Secondary | CAP, length of mechanical ventilation | Days | No | |
Secondary | CAP, SOFA respiratory score > 2 | 28 days | No | |
Secondary | CAP, respiratory component of severe sepsis criteria | 28 days | No | |
Secondary | CAP, hospitalized | 24 hours | No | |
Secondary | CAP, length of hospitalization | Days | No | |
Secondary | CAP, ICU admission | 28 days | No | |
Secondary | CAP, length of ICU stay | Days | No | |
Secondary | CAP, Disposition | 28 days | No | |
Secondary | CAP, ALI | 28 days | No | |
Secondary | CAP, ARDS | 28 days | No | |
Secondary | CAP, time to ARDS | days | No | |
Secondary | CAP, time to ALI | Days | No | |
Secondary | CAP, PORT score | enrollment | No | |
Secondary | CAP, PORT score | 24 hours | No |
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