The INFUSE Trial - Intervening With Platelet Transfusions in Sepsis

NCT03090919 | Withdrawn DMC

• 1 other identifier: 16-0784-F6A
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis; Thrombocytopenia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Transfusion effects on cytokines

  72 Hours

• Incidence of Serious Adverse Events

  30 days

• Transfusion effects on coagulation

  72 Hours

• Transfusion effects on platelet number

  72 Hours

Study Arms (2)

Saline

PLACEBO COMPARATOR

Subjects randomized to the Saline arm will receive 250cc of physiological saline.

Other: Saline

Platelet transfusion

EXPERIMENTAL

Subjects randomized to platelet transfusion will receive a unit of platelets (\~250cc in volume).

Biological: Platelet transfusion

Interventions

Platelet transfusion BIOLOGICAL

Platelet transfusion

Saline OTHER

Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Susan Smyth: lead

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (5)

• 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.

  PMID: 21075430 BACKGROUND

• 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.

  PMID: 21071526 BACKGROUND

• 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.

  PMID: 18084977 BACKGROUND

• 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.

  PMID: 26956172 BACKGROUND

• 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.

  PMID: 24150174 BACKGROUND

MeSH Terms

Conditions

Sepsis; Thrombocytopenia

Interventions

Platelet Transfusion; Sodium Chloride

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Blood Component Transfusion; Blood Transfusion; Biological Therapy; Therapeutics; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Susan S Smyth, MD PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principle Investigators

Model Details: Subjects will be randomized to recieve either a platelet transfusion or a saline transfusion.

Study Record Dates

• First Submitted: January 24, 2017
• First Posted: March 27, 2017
• Study Start: January 3, 2017
• Primary Completion: May 31, 2021
• Study Completion: May 31, 2021
• Last Updated: July 28, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)