- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT01355042
Studies of Blood DNA in Patients With Severe Infection DYNAMICS (DYNAMICS)
DYNAMICS: DNA as a Prognostic Marker in ICU Patients Study
연구 개요
상세 설명
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
연구 유형
등록 (실제)
연락처 및 위치
연구 장소
-
-
Alberta
-
Calgary, Alberta, 캐나다
- Alberta Health Services -- Foothills Hospital
-
-
British Columbia
-
Vancouver, British Columbia, 캐나다, V6Z 1Y6
- St. Paul's Hospital
-
-
Ontario
-
Hamilton, Ontario, 캐나다
- Hamilton Health Sciences: General Site
-
Hamilton, Ontario, 캐나다
- St Joseph's Health Care
-
Ottawa, Ontario, 캐나다
- The Ottawa Hospital
-
-
Quebec
-
Laval, Quebec, 캐나다
- Centre Hospitalier De L'Universite Laval
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
샘플링 방법
연구 인구
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
---|
Severe Sepsis and Septic Shock
|
Other Critical Ill with or without Shock
Severe Trauma, Neurological Injury, Other Shock (not Septic)
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Patricia Liaw, PhD, Thrombosis and Atherosclerosis Research Institute
간행물 및 유용한 링크
일반 간행물
- Jackson Chornenki NL, Coke R, Kwong AC, Dwivedi DJ, Xu MK, McDonald E, Marshall JC, Fox-Robichaud AE, Charbonney E, Liaw PC. Comparison of the source and prognostic utility of cfDNA in trauma and sepsis. Intensive Care Med Exp. 2019 May 22;7(1):29. doi: 10.1186/s40635-019-0251-4.
- Grin PM, Dwivedi DJ, Chathely KM, Trigatti BL, Prat A, Seidah NG, Liaw PC, Fox-Robichaud AE. Low-density lipoprotein (LDL)-dependent uptake of Gram-positive lipoteichoic acid and Gram-negative lipopolysaccharide occurs through LDL receptor. Sci Rep. 2018 Jul 12;8(1):10496. doi: 10.1038/s41598-018-28777-0.
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- CIHR-220268
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .