Pharmacogenomic Biomarker Study for Recombinant Human Activated Protein C Treatment in Severe Sepsis
NCT ID: NCT01486524
Last Updated: 2011-12-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
3000 participants
OBSERVATIONAL
2011-10-31
2012-04-30
Brief Summary
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Detailed Description
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To control for differences in standard of care in different countries and medical centers, the selection of matched control patients will be performed within each cohort. Control patients will be selected to match the DrotAA-treated patients using an algorithm that matches on baseline demographic and disease characteristics that may have influenced the decision to give DrotAA or that may impact survival. A propensity score (the likelihood for having received DrotAA treatment) will be derived using the matching variables that are common in all cohorts. The number of matched control patients for each treated patient will be variable, up to a maximum of 3.
The selection of the control patients via the matching algorithm will be conducted by an independent clinical research organization (CRO) in a blinded manner - specifically without knowledge of survival outcome, other outcome data, and genotype. A two-phase transfer of data from each center will be implemented to ensure that the selection of matched control patients is implemented in a blinded manner. The first step will involve the transfer of the baseline data for all variables needed to conduct the matching. Once the control patients have been identified for each cohort, the outcomes data will be transferred to the CRO in the second phase of data transfer.
Centralized genotyping using a validated Taqman®-based analytical method will be conducted on the DNA samples for all matched patients. The genotyping laboratory will be blinded to treatment and outcome.
The total number of patients in the available cohorts is \>23,000, with approximately 800 who have received DrotAA as part of their standard ICU-based care. After applying eligibility criteria to all patients and selecting the matched control patients, it is expected that the final analysis will include approximately 3000 patients.
Conditions
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Keywords
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Study Design
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RETROSPECTIVE
Study Groups
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DrotAA Treatment Group
Patients with severe sepsis at high risk of death (INDICATED patients) who received treatment with drotrecogin alfa (activated (DrotAA) as part of standard care in ICU. The standard dosing regimen for DrotAA is 96 hours of continuous infusion at a dose of 24 ug/kg/hour. DrotAA is also known as recombinant human activated protein C.
No interventions assigned to this group
Control Group (non-DrotAA treated)
Patients with severe sepsis at high risk of death (INDICATED patients) who did not receive DrotAA treatment as part of their standard care in an ICU. The Control group patients will be selected to match the DrotAA-treated patients based on numerous clinical covariates, including propensity score (for DrotAA treatment).
No interventions assigned to this group
Eligibility Criteria
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Inclusion Criteria
2. Severe sepsis (must meet a, b, and c below)
* Suspected or proven infection
* Systemic Inflammatory Response Syndrome (SIRS)(must meet 2 of 4 criteria)
* Temperature \< 36°C or \> 38°C
* Heart rate \> 90 beats/minute
* Respiratory rate \> 20 breaths/minute or PaC02 \< 32 mm Hg) or on mechanical ventilation
* White blood cell count \< 4,000/mm3 or \> 12,000/mm3
* At least one organ dysfunction due to sepsis based on definitions of clinically significant organ dysfunction
* Cardiovascular dysfunction \[must meet one of (1), (2), or (3) below\]:
* Systolic blood pressure ≤ 90 mmHg and pH ≤ 7.3
* Mean arterial pressure ≤ 70 mmHg and pH ≤ 7.3
* Reported use of a vasopressor alone is sufficient evidence of shock
* Pulmonary dysfunction: PaO2/FiO2 ≤ 300 mmHg
* Central Nervous System dysfunction: Glasgow Coma Scale ≤ 12
* Coagulation dysfunction: platelets ≤ 80,000/mm3
* Renal dysfunction: creatinine ≥ 2.0 mg/dL
* Hepatic dysfunction: bilirubin ≥ 2.0 mg/dL
3. High risk of death (one of a, b, or c below)
* APACHE II ≥ 25
* SAPS II ≥ 54
* Multiple organ dysfunction - two or more clinically significant organ dysfunctions (as defined above), which have occurred within 2 days of each other
4. Platelet counts ≥ 30,000/mm3
5. DrotAA status known
Exclusion Criteria
2. Patients enrolled in local cohort more than 2 years before Xigris \[drotrecogin alfa activated)\] was commercially available
18 Years
ALL
No
Sponsors
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Sirius Genomics Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Djillali Annane, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Versailles
Alexandra DJ Mancini, MSc
Role: STUDY_DIRECTOR
Sirius Genomics Inc.
Locations
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Emory University School of Medicine
Atlanta, Georgia, United States
Johns Hopkins University, Bayview Medical Center
Baltimore, Maryland, United States
Harvard University School of Public Health
Boston, Massachusetts, United States
Vanderbilt University Schoo of Medicine
Nashville, Tennessee, United States
University of British Columbia and Providence Health Care, St. Paul's Hospital
Vancouver, British Columbia, Canada
University of Versailles, Hospital Raymond Poincaré (AP-HP)
Garches, , France
Université Paris Descartes, Sorbonne Paris Cité, Cochin Hotel-Dieu University Hospital
Paris, , France
Imperial College London, Charing Cross Hospital
London, , United Kingdom
Countries
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References
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Annane D, Mira JP, Ware LB, Gordon AC, Hinds CJ, Christiani DC, Sevransky J, Barnes K, Buchman TG, Heagerty PJ, Balshaw R, Lesnikova N, de Nobrega K, Wellman HF, Neira M, Mancini ADJ, Walley KR, Russell JA. Pharmacogenomic biomarkers do not predict response to drotrecogin alfa in patients with severe sepsis. Ann Intensive Care. 2018 Jan 31;8(1):16. doi: 10.1186/s13613-018-0353-2.
Other Identifiers
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SGX301
Identifier Type: -
Identifier Source: org_study_id