Studies of Blood DNA in Patients With Severe Infection DYNAMICS

This study is currently recruiting participants.
Verified September 2012 by Hamilton Health Sciences Corporation
Sponsor:
Information provided by (Responsible Party):
Alison Fox-Robichaud, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier:
NCT01355042
First received: May 16, 2011
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

Severe sepsis (ie. life-threatening infections) is triggered by harmful microorganisms or their toxins in the blood or tissues. These harmful agents damage the lining of blood vessels which can lead to inflammation, blood clot formation, and vessel obstruction. In Canada, there are approximately 90,000 patients with severe sepsis each year. Of these, 30% to 50% will die. The identification of highly reliable outcome predictors in severe sepsis patients is important for several reasons including: to help describe the severity of sepsis, to classify patients for enrollment in clinical studies, and to monitor a patient's response to treatment and procedures. In the investigators lab, the investigators examined the incremental usefulness of adding multiple biomarkers to clinical scoring systems for predicting ICU mortality in patients with severe sepsis. In a preliminary study of 80 patients with sepsis, the investigators found that high levels of plasma DNA predicted ICU death better than any other clinical or biological factor. In this grant, the investigators propose to confirm these findings in an external group of 400 patients in a blinded fashion. The investigators also plan to study how plasma DNA levels change over time and whether high plasma DNA levels can be used to distinguish sepsis from other critically ill conditions. For this the investigators will compare the investigators septic patients to a cohort of 600 patients in the ICU with other conditions. The investigators believe this research has the potential to significantly improve the management and treatment of septic patients.


Condition
Sepsis
Shock
Trauma

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: DYNAMICS: DNA as a Prognostic Marker in ICU Patients Study

Resource links provided by NLM:


Further study details as provided by Hamilton Health Sciences Corporation:

Biospecimen Retention:   Samples With DNA

plasma


Estimated Enrollment: 1000
Study Start Date: November 2010
Estimated Study Completion Date: September 2015
Groups/Cohorts
Severe Sepsis and Septic Shock
Other Critical Ill with or without Shock
Severe Trauma, Neurological Injury, Other Shock (not Septic)

Detailed Description:

DYNAMICS STUDY (DNA as prognostic marker in ICU patients)

Principal Investigator: Patricia Liaw, PhD (McMaster University) Coinvestigator: Alison Fox-Robichaud, MD (McMaster University) Funding source: CIHR, 2010-2015 Budget: $794,086

One-page Protocol summary This is a new 5-year CIHR funded multi-centre prospective observational study. The overall objective is to gain insight into the pathophysiology of plasma DNA (ie. cell-free DNA) in severe sepsis patients and in other critically ill patients. In our pilot study of 80 severe sepsis patients, we found that plasma DNA had extremely high prognostic utility in this patient population. Using Receiver Operating Characteristic (ROC) curves in a multivariate logistic model, we demonstrated that the Area Under the Curve (AUC) for plasma DNA is 0.96 (95% CI 0.93-1.00). Furthermore, plasma DNA levels obtained at "day 1" (ie. within 24 hours of meeting the inclusion criteria for severe sepsis) did not differ significantly from the levels measured in subsequent days. In other words, plasma DNA levels in nonsurvivors were high at "day 1" and remained high; plasma DNA levels in survivors were low at "day 1" and remained low. These finding suggests that at study inclusion for severe sepsis, the nonsurvivor patients had already reached "a point of no return" (with the standard of care available at the time the patients in the pilot study were recruited).

We plan to validate the prognostic utility of plasma DNA prospectively in an independent cohort of severe sepsis patients (n=400). We will also study a broad cohort of non-septic ICU patients (n=600) to determine if elevations in plasma DNA are specific to severe sepsis, or if it is more generally associated with high mortality risk. These non-septic ICU patients include the following: multiple trauma, shock on presentation, neurosurgery, aneurysm, intracranial hemorrhage, burns). The overall research coordinator for this study is Ellen McDonald. Participating centres include Hamilton (Patricia Liaw, Alison Fox-Robichaud, Deborah Cook), Ottawa (Laurlyn McIntyre), London (Claudio Martin, Doug Fraser), Vancouver (Peter Dodek), Toronto (John Marshall, Jennifer Tsang), Laval Quebec (Francois Lallouche), and Calgary (Brent Winston).

Clinical data will be collected daily during the first week, then once a week thereafter for the duration of the patients' stay in the ICU. Blood sample will also be collected on the same schedule except that weekend blood samples will be skipped. Freezerworks Unlimited will be used for barcoding and tracking of all plasma samples. All samples will be shipped to Hamilton for biomarker analyses. Clinical data will be managed with the iDataFax software with statistical support from Janice Pogue at the Population Health and Research Institute (Hamilton). The primary outcome is ICU mortality. The secondary outcomes are (a) the temporal relationships between plasma DNA levels and other markers of inflammation and blood clotting, and (b) the temporal relationships between plasma DNA levels and clinical parameters (e.g. SOFA and MODS scores, interventions, use of blood products and plasma expanders).

This study was approved by the Research Ethics Board at the Hamilton Health Sciences in November 2010. Deferred consent has been approved. Although we are not performing any DNA sequencing analyses on the patient samples (ie. we are simply quantifying how much DNA is in the plasma), we are also collecting Paxgene DNA tubes in the event that future as-yet-undetermined studies require DNA for gene sequencing studies. Our local Ethics Board has approved a separate Genetic Consent form to request and extra blood samples for Paxgene DNA tubes. As of May 2012 we have completed recruitment in the sepsis arm. We are starting to close some sites to enrolment as we near study completion

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients admitted to academic intensive care units

Criteria

Inclusion Criteria:

  • admitted to an intensive care unit with either sepsis or other critical illness in previous 24 hrs

Exclusion Criteria:

  • less than 18 yrs old
  • not expected to survive 72 hrs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01355042

Contacts
Contact: Patricia Liaw, PhD 9055212100 ext 40788 patricia.liaw@taari.ca
Contact: Alison Fox-Robichaud, MD 9055259140 ext 22782 afoxrob@mcmaster.ca

Locations
Canada, Alberta
Alberta Health Services -- Foothills Hospital Recruiting
Calgary, Alberta, Canada
Contact: Brent Winston, MD    403 220 4331    bwinston@ucalgary.ca   
Principal Investigator: Brent Winston, MD         
Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z 1Y6
Contact: Betty Jean Ashley       bjashley@cheos.ubc.ca   
Principal Investigator: Peter Dodek, MD         
Canada, Ontario
Hamilton Health Sciences: General Site Recruiting
Hamilton, Ontario, Canada
Contact: Ellen McDonald, RN       emcdonal@mcmaster.ca   
Principal Investigator: Alison Fox-Robichaud, MD         
St Joseph's Health Care Active, not recruiting
Hamilton, Ontario, Canada
The Ottawa Hospital Active, not recruiting
Ottawa, Ontario, Canada
Canada, Quebec
Centre Hospitalier de l'Universite Laval Recruiting
Laval, Quebec, Canada
Contact: Marie-Claude Ferland       marie-claude.ferland@criucpq.ulaval.ca   
Principal Investigator: Francois Lellouche, MD         
Sponsors and Collaborators
Alison Fox-Robichaud
Investigators
Principal Investigator: Patricia Liaw, PhD Thrombosis and Atherosclerosis Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Alison Fox-Robichaud, Physician, Hamilton Health Sciences Corporation
ClinicalTrials.gov Identifier: NCT01355042     History of Changes
Other Study ID Numbers: CIHR-220268
Study First Received: May 16, 2011
Last Updated: September 12, 2012
Health Authority: Canada: Canadian Institutes of Health Research

Additional relevant MeSH terms:
Sepsis
Shock
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes

ClinicalTrials.gov processed this record on April 17, 2014