Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor (XANTHIPPE)
Community Acquired Pneumonia
Hospital Acquired Pneumonia
Acute Lung Injury
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||XANTHIPPE: Examining the Effect of Ticagrelor on Platelet Activation, Platelet-Leukocyte Aggregates, and Acute Lung Injury in Pneumonia|
- Platelet-Leukocyte Aggregates [ Time Frame: 30 day ] [ Designated as safety issue: No ]Platelet-leukocyte aggregates will be measured by flow cytometry.
- Platelet function tests [ Time Frame: 30 day ] [ Designated as safety issue: No ]Platelet function will be monitored by aggregation and by measuring markers of platelet secretion
- Systemic inflammation [ Time Frame: 30 day ] [ Designated as safety issue: No ]Markers of inflammation will be measured in plasma or serum
- Lung function [ Time Frame: During hospital stay up to 30 days. ] [ Designated as safety issue: No ]
In non-ventilated patients, spirometry, maximal voluntary ventilation, maximal inspiratory and expiratory pressure generation, and P/F ratio (PaO2/FiO2)
In ventilated patients, respiratory system static compliance, airway resistance, oxygenation index (PaO2/FiO2), and maximal inspiratory and expiratory pressure generation.
- Significant Bleeding Event [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
The PLATO definition of bleeding will be used to classify events. Life-threatening bleeding is defined as fatal or intracranial or intrapericardial with cardiac tamponade or hypovolemic shock, or severe hypotension requiring pressors or surgery, decrease in hemoglobin of >50mg/ml or transfusion of ≥ 4units of packed red blood cells(pRBCs).
Major bleeding is defined as significantly disabling (intraocular with permanent vision loss), 30 - 50 mg/ml decrease in hemoglobin, or transfusion of 2 - 3 U pRBCs.
Minor bleeding will be captured using PLATO bleeding definition of bleeding that requires medication intervention to stop or treat.
- Mechanical Ventilation [ Time Frame: 30 days ] [ Designated as safety issue: No ]mechanical ventilation or ventilator free days at day 30
- Sepsis [ Time Frame: 30 days ] [ Designated as safety issue: No ]Diagnosis of Sepsis
- Mortality [ Time Frame: 30 days ] [ Designated as safety issue: No ]
- Major Cardiovascular Event [ Time Frame: 30 days ] [ Designated as safety issue: No ]Major cardiovascular event can by myocardial infarction, stroke, or life threatening arrhythmia.
|Study Start Date:||June 2013|
|Study Completion Date:||June 2016|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
180 mg orally once and then 90 mg orally daily for 7 days or until hospital discharge if sooner
Other Name: Brilinta
Placebo Comparator: placebo
One loading dose and then daily for 7 days or until hospital discharge if sooner
While it is well established that platelets are integral to hemostasis, more recent evidence points to an important role for platelets in inflammation and immunity. Platelet activation and sequestration in pulmonary tissue is a key feature in inflammatory or infectious states such as sepsis and acute respiratory distress syndrome (ARDS). Platelets may mediate acute lung injury (ALI) by recruiting neutrophils, triggering neutrophil extracellular DNA nets, and releasing granule contents and microparticles. Anti-platelet therapy in this setting may prevent platelet activation, platelet - leukocyte aggregate formation, and inflammation.
The objective of this pilot study is to determine if ticagrelor therapy in individuals with pneumonia reduces markers of platelet activation, platelet-leukocyte aggregates, inflammation, acute lung injury, and lung mechanics. Because the benefit of anti-platelet therapy may the greatest in patients with more significant lung injury, the investigators will enroll patients with community-acquired pneumonia (CAP) requiring hospitalization or patients with hospital acquired pneumonia (HAP) within 48 hours of diagnosis. On study day 1, subjects will be randomized to receive ticagrelor (180 mg load and 90 mg BID) or placebo. Study medication (ticagrelor or placebo) will be administered twice daily on days 2 - 7 or until hospital discharge, if sooner than 7 days. Blood will be collected and assays performed on day 1 prior to study medication administration (baseline), day 2, 3, 7, day of discharge (if before 7 days), and 30 days for analysis of platelet count, markers of platelet activation, platelet - leukocyte interactions, biomarkers of inflammation, and measurements of lung mechanics.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01883869
|United States, Kentucky|
|University of Kentucky Hospitals|
|Lexington, Kentucky, United States, 40536|
|University of Kentucky Hospital|
|Lexington, Kentucky, United States, 40536|
|Principal Investigator:||Susan S Smyth, MD PhD||University of Kentucky|