Clinical trial NCT03090919: The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis
Official title: The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Sepsis
Thrombocytopenia
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2017-03-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized to recieve either a platelet transfusion or a saline transfusion.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Biomarkers for vascular integrity
timeFrame: 24 Hours
measure: Biomarkers for inflammation
timeFrame: 24 Hours
Secondary outcomes:
measure: Transfusion effects on cytokines
timeFrame: 72 Hours
measure: Incidence of Serious Adverse Events
timeFrame: 30 days
measure: Transfusion effects on coagulation
timeFrame: 72 Hours
measure: Transfusion effects on platelet number
timeFrame: 72 Hours
Other outcomes:
Locations:
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Susan S Smyth, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.