Observational Study of Sepsis and Pneumonia to Develop Diagnostic Tests

NCT00258869 | Unknown DMC

• 2 other identifiers: 0001U01AI066569
• Study Type: observational
• Target: 1,200
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Sepsis; Septicemia; Sepsis Syndrome; Shock, Septic; Community Acquired Pneumonia

Keywords

prospective studies; biological assay; body weights and measures; chemistry, analytical; microchip analytical procedures; spectrum analysis, mass; molecular diagnostic techniques; microbiological techniques; drug administration schedule; data collection; statistics; gene expression profiling; sequence analysis; human experimentation; immunoassay; Trauma severity indices; Glasgow Coma score; Outcome assessment; mortality; computer models; decision modeling; linear models; logistic models; immunologic model; mathematical model; non-linear models; early diagnosis; diagnosis, computer assisted; medical informatics; prognosis; registries; computational biology; systems biology

Outcome Measures

Primary Outcomes (3)

• Death

  Day 3

• Septic Shock

  Day 3

• Severe Sepsis

  Day 3

Secondary Outcomes (101)

• Time to death

  28 days

• Death

  Day 5

• Death

  Day 7

• Death

  Day 28

• Time to severe sepsis

  28 days

Study Arms (1)

1

Emergency department patients with sepsis

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Emergency department patients \> 6 years of age

You may qualify if:

• \. Patient has known or acute infection or suspected infection AND patient must meet at least 2 of the following 4 criteria to be enrolled
• A core temperature of \>= 38°C (100.4°F) or \<= 36°C (96.8°F)
• 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
• 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
• 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

You may not qualify if:

• Patient is less than 6 years of age.
• 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
• Human immunodeficiency virus (HIV) infection with a last known CD4 count of \<50 mm3
• Acute presence of a cerebral vascular event, active gastrointestinal hemorrhage, seizure (acute episode), drug overdose, burn injury, trauma
• Patient is pregnant

Sponsors & Collaborators

• National Center for Genome Resources: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Duke University: collaborator
• Henry Ford Hospital: collaborator
• Durham VA Medical Center: collaborator
• Pfizer: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (3)

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Durham VA Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Related Publications (16)

• Perlee LT, Christiansen J, Dondero R, Grimwade B, Lejnine S, Mullenix M, Shao W, Sorette M, Tchernev VT, Patel DD, Kingsmore SF. Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics. Proteome Sci. 2004 Dec 15;2:9. doi: 10.1186/1477-5956-2-9. eCollection 2004.

  PMID: 15598355 BACKGROUND

• 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. doi: 10.1038/nbt0402-359.

  PMID: 11923841 BACKGROUND

• Kingsmore SF, Patel DD. Multiplexed protein profiling on antibody-based microarrays by rolling circle amplification. Curr Opin Biotechnol. 2003 Feb;14(1):74-81. doi: 10.1016/s0958-1669(02)00019-8.

  PMID: 12566005 BACKGROUND

• Kaukola T, Satyaraj E, Patel DD, Tchernev VT, Grimwade BG, Kingsmore SF, Koskela P, Tammela O, Vainionpaa L, Pihko H, Aarimaa T, Hallman M. Cerebral palsy is characterized by protein mediators in cord serum. Ann Neurol. 2004 Feb;55(2):186-94. doi: 10.1002/ana.10809.

  PMID: 14755722 BACKGROUND

• 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. doi: 10.1111/j.1572-0241.2005.40819.x.

  PMID: 15667502 BACKGROUND

• 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. doi: 10.1586/14789450.2.5.669.

  PMID: 16209647 BACKGROUND

• Rivers EP, Nguyen HB, Huang DT, Donnino M. Early goal-directed therapy. Crit Care Med. 2004 Jan;32(1):314-5; author reply 315. doi: 10.1097/01.CCM.0000104937.09370.53. No abstract available.

  PMID: 14707615 BACKGROUND

• 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. doi: 10.1056/NEJMoa010307.

  PMID: 11794169 BACKGROUND

• 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. doi: 10.1503/cmaj.050632.

  PMID: 16247103 BACKGROUND

• 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. doi: 10.1097/01.ccm.0000129488.54282.1a.

  PMID: 15241104 BACKGROUND

• O'Brien LA, Gupta A, Grinnell BW. Activated protein C and sepsis. Front Biosci. 2006 Jan 1;11:676-98. doi: 10.2741/1827.

  PMID: 16146761 BACKGROUND

• Tsalik EL, Khine A, Talebpour A, Samiei A, Parmar V, Burke TW, Mcclain MT, Ginsburg GS, Woods CW, Henao R, Alavie T. Rapid, Sample-to-Answer Host Gene Expression Test to Diagnose Viral Infection. Open Forum Infect Dis. 2019 Oct 30;6(11):ofz466. doi: 10.1093/ofid/ofz466. eCollection 2019 Nov.

  PMID: 34150923 DERIVED

• Tsalik EL, Henao R, Montgomery JL, Nawrocki JW, Aydin M, Lydon EC, Ko ER, Petzold E, Nicholson BP, Cairns CB, Glickman SW, Quackenbush E, Kingsmore SF, Jaehne AK, Rivers EP, Langley RJ, Fowler VG, McClain MT, Crisp RJ, Ginsburg GS, Burke TW, Hemmert AC, Woods CW; Antibacterial Resistance Leadership Group. Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test. Crit Care Med. 2021 Oct 1;49(10):1651-1663. doi: 10.1097/CCM.0000000000005085.

  PMID: 33938716 DERIVED

• Tsalik EL, Langley RJ, Dinwiddie DL, Miller NA, Yoo B, van Velkinburgh JC, Smith LD, Thiffault I, Jaehne AK, Valente AM, Henao R, Yuan X, Glickman SW, Rice BJ, McClain MT, Carin L, Corey GR, Ginsburg GS, Cairns CB, Otero RM, Fowler VG Jr, Rivers EP, Woods CW, Kingsmore SF. An integrated transcriptome and expressed variant analysis of sepsis survival and death. Genome Med. 2014 Nov 26;6(11):111. doi: 10.1186/s13073-014-0111-5. eCollection 2014.

  PMID: 25538794 DERIVED

• Glickman SW, Cairns CB, Otero RM, Woods CW, Tsalik EL, Langley RJ, van Velkinburgh JC, Park LP, Glickman LT, Fowler VG Jr, Kingsmore SF, Rivers EP. Disease progression in hemodynamically stable patients presenting to the emergency department with sepsis. Acad Emerg Med. 2010 Apr;17(4):383-90. doi: 10.1111/j.1553-2712.2010.00664.x.

  PMID: 20370777 DERIVED

• Tsalik EL, Jones D, Nicholson B, Waring L, Liesenfeld O, Park LP, Glickman SW, Caram LB, Langley RJ, van Velkinburgh JC, Cairns CB, Rivers EP, Otero RM, Kingsmore SF, Lalani T, Fowler VG, Woods CW. Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis. J Clin Microbiol. 2010 Jan;48(1):26-33. doi: 10.1128/JCM.01447-09. Epub 2009 Oct 21.

  PMID: 19846634 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

PaxGene whole blood tubes (RNA and DNA), EDTA plasma, serum (subset), microbiologic isolates

MeSH Terms

Conditions

Sepsis; Systemic Inflammatory Response Syndrome; Shock, Septic; Community-Acquired Pneumonia; Body Weight; Arachnodactyly; Disease

Condition Hierarchy (Ancestors)

Infections; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Community-Acquired Infections; Pneumonia; Respiratory Tract Infections; Respiratory Tract Diseases; Signs and Symptoms; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Stephen F Kingsmore, MB ChB BAO

  National Center for Genome Resources

  PRINCIPAL INVESTIGATOR

• Vance Jr G Fowler, MD

  Duke University

  STUDY DIRECTOR

• Emanuel P Rivers, MD

  Henry Ford Hospital

  STUDY DIRECTOR

• Christopher W Woods, MD

  Duke University

  STUDY DIRECTOR

• Ralph G Corey, MD

  Duke University

  STUDY DIRECTOR

• Ronny Otero, MD

  Henry Ford Hospital

  STUDY DIRECTOR

• Brian W Grinnell, PhD

  Eli Lilly and Company

  STUDY DIRECTOR

• Brian T Edmonds, PhD

  Eli Lilly and Company

  STUDY DIRECTOR

• Mu Wang, PhD

  INCAPS

  STUDY DIRECTOR

• James R Ludwig, PhD

  INCAPS

  STUDY DIRECTOR

Central Study Contacts

Stephen F Kingsmore, MB ChB BAO

CONTACT

505 995 4466; sfk@ncgr.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 23, 2005
• First Posted: November 28, 2005
• Study Start: December 1, 2005
• Primary Completion: July 1, 2010
• Study Completion: July 1, 2010
• Last Updated: November 9, 2010

Record last verified: 2009-01

Locations

US (3)