The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis

Study Overview
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Brief Summary
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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. 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.

Detailed Description
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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.

Official Title
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The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis

Conditions
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Sepsis, Thrombocytopenia

Intervention / Treatment
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* Biological: Platelet transfusion
* Other: Saline


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to recieve either a platelet transfusion or a saline transfusion.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline<br>Subjects randomized to the Saline arm will receive 250cc of physiological saline. | Other: Saline<br> <br> |
| Experimental: Platelet transfusion<br>Subjects randomized to platelet transfusion will receive a unit of platelets ( 250cc in volume). | Biological: Platelet transfusion<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers for vascular integrity | 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. | 24 Hours | 
| Biomarkers for inflammation | 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion effects on cytokines | 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. | 72 Hours | 
| Incidence of Serious Adverse Events | 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. | 30 days | 
| Transfusion effects on coagulation | 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. | 72 Hours | 
| Transfusion effects on platelet number | 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. | 72 Hours |