- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03090919
The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis (INFUSE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Sepsis is life-threatening and dysregulated response to infection that results in endothelial activation and dysfunction that leads to systemic microvascular leak and multiple-organ failure. Emerging evidence indicates that platelets occupy a central role in maintaining the balance between vascular health and the response to environmental changes and vascular injury. Platelets are essential for vascular development and required for normal endothelial integrity. Platelets also function at the interface between thrombosis and inflammation. This study will identify patients that have sepsis with thrombocytopenia and randomize them to receive a unit of platelets or an equivalent volume of saline.
Our overall hypotheis is that normal platelet function is required to maintain vascular integrity and can be at least partially restored over the first 24 hours by platelet transfusion in septic patients with thrombocytopenia.
Study Type
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
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Kentucky
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Lexington, Kentucky, United States, 40536
- University of Kentucky
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- Provision of informed consent prior to any study specific procedures
- Female and/or male, age >18 years
- Diagnosis of sepsis based on the Third International Consensus Definitions for Sepsis and Septic Shock
- Platelet count ≤ 50,000/μL
Exclusion Criteria
- Active major bleeding requiring blood transfusion
- Other causes of thrombocytopenia such as idiopathic thrombocytopenic purpura, high clinical suspicion for heparin-induced thrombocytopenia (or other form of consumptive coagulopathy).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Saline
Subjects randomized to the Saline arm will receive 250cc of physiological saline.
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Experimental: Platelet transfusion
Subjects randomized to platelet transfusion will receive a unit of platelets (~250cc in volume).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biomarkers for vascular integrity
Time Frame: 24 Hours
|
The ratio of Angiopoietin-2 to Angiopoietin-1 is used as a measurement of vascular integrity.
We will determine the change in this ratio by measuring Angiopoietin-2 (pg/mL) and Angiopoietin-1 (pg/mL) at baseline (before infusion) and 24 hours after infusion and compare between the patients receiving a unit of platelets versus the patients receiving saline.
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24 Hours
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Biomarkers for inflammation
Time Frame: 24 Hours
|
IL-6 and TNF-alpha are commonly measured as biomarkers for inflammation.
We will measure the change in concentrations (pg/mL) of IL-6 and TNF-alpha between baseline and 24 hours and compare between the population receiving a unit of platelets versus the population receiving saline.
|
24 Hours
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Transfusion effects on cytokines
Time Frame: 72 Hours
|
Changes in cytokine (e.g.
IL-1beta) concentrations (pg/mL) will be measured at baseline (prior to transfusion) and up to 72 hours after transfusion and compared between the population receiving a unit of platelets versus the population receiving saline.
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72 Hours
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Incidence of Serious Adverse Events
Time Frame: 30 days
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Each subject will be monitored for serious adverse events (e.g.
death, rehospitalization) for 30 days following the platelet/saline transfusion.
Outcome data will be compared between the platelet transfusion arm and the placebo arm.
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30 days
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Transfusion effects on coagulation
Time Frame: 72 Hours
|
Changes in a biomarker for coagulation (prothrombin fragment 1-2) will be measured (pg/mL) at baseline (prior to transfusion) and up to 72 hours after transfusion and compared between the population receiving a unit of platelets versus the population receiving saline.
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72 Hours
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Transfusion effects on platelet number
Time Frame: 72 Hours
|
Changes in platelet count (platelets/mm^3 blood) at baseline (prior to transfusion) and up to 72 hours after transfusion and compared between the population receiving a unit of platelets versus the population receiving saline.
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72 Hours
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Susan S Smyth, MD PhD, University of Kentucky
Publications and helpful links
General Publications
- Li Z, Yang F, Dunn S, Gross AK, Smyth SS. Platelets as immune mediators: their role in host defense responses and sepsis. Thromb Res. 2011 Mar;127(3):184-8. doi: 10.1016/j.thromres.2010.10.010. Epub 2010 Nov 13.
- Hui P, Cook DJ, Lim W, Fraser GA, Arnold DM. The frequency and clinical significance of thrombocytopenia complicating critical illness: a systematic review. Chest. 2011 Feb;139(2):271-278. doi: 10.1378/chest.10-2243. Epub 2010 Nov 11.
- Sharma B, Sharma M, Majumder M, Steier W, Sangal A, Kalawar M. Thrombocytopenia in septic shock patients--a prospective observational study of incidence, risk factors and correlation with clinical outcome. Anaesth Intensive Care. 2007 Dec;35(6):874-80. doi: 10.1177/0310057X0703500604.
- Claushuis TA, van Vught LA, Scicluna BP, Wiewel MA, Klein Klouwenberg PM, Hoogendijk AJ, Ong DS, Cremer OL, Horn J, Franitza M, Toliat MR, Nurnberg P, Zwinderman AH, Bonten MJ, Schultz MJ, van der Poll T; Molecular Diagnosis and Risk Stratification of Sepsis Consortium. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients. Blood. 2016 Jun 16;127(24):3062-72. doi: 10.1182/blood-2015-11-680744. Epub 2016 Mar 8.
- Xiang B, Zhang G, Guo L, Li XA, Morris AJ, Daugherty A, Whiteheart SW, Smyth SS, Li Z. Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway. Nat Commun. 2013;4:2657. doi: 10.1038/ncomms3657.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 16-0784-F6A
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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