Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor

• Status: Completed
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

The hypothesis to be tested is that ticagrelor (Brilinta™) will reduce platelet activation and markers of inflammation in patients with pneumonia.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Kentucky
• Treatments: Ticagrelor

Criteria

Inclusion Criteria:

• Subjects must be 18 years of age or older

• Subjects must diagnosed with Community acquired pneumonia (CAP) or hospital acquired pneumonia (HAP) within 48 hours of diagnosis or presentation to hospital.

• Pneumonia will be defined as patients with a new radiographic finding(s) consistent with pneumonia and at least two of the following signs.

1. Cough

2. Fever: axillary temperature >37.5ºC or tympanic temperature >38.5ºC

3. Hypothermia: axillary temperature <34ºC or tympanic temperature <35ºC.

4. Purulent sputum production or respiratory secretion.

5. Total peripheral white blood cell (WBC) count >10,000/mm3; or >15% band forms, regardless of total peripheral white count; or leucopenia with total WBC < 4500/mm

6. Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony)

7. Hypoxemia - defined as partial O2 pressure <60mmHg while the patient was breathing normal air or a decrease in the partial O2 pressure of >= 25% from an initial range.

Exclusion Criteria:

1. Contraindication to ticagrelor (hypersensitivity or reaction to ticagrelor or another P2Y12 antagonist)

2. Active bleeding or major bleeding history (e.g. intracranial bleeding)

3. Clinically important anemia or thrombocytopenia (platelet count <30)

4. Surgery within 30 days or anticipated major surgery (Thoracic, Abdominal, Brain; placement of lines, tracheostomy, and chest tubes are not considered major).

5. Oral anticoagulant therapy that cannot be stopped.

6. Inability or unwillingness of treating physician to reduce dose of aspirin to 81mg.

7. Fibrinolytic therapy in the last 24 hours.

8. Increased risk of bradycardic events - 2nd or 3rd degree heart block, bradycardia induced syncope - unless pacemaker in place.

9. Underlying immunodeficiency (HIV, neutropenia, receiving immunomodulating agents, active hematologic malignancy, functional or anatomical asplenia and hypogammaglobulinemia).

10. Moderate or severe liver disease defined by Child Pugh score >7 using data from outpatient setting or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 fold upper limits of normal.

11. Renal dialysis

12. Concomitant therapy with strong CYP3A inhibitors; ketoconazole, itraconazole, voriconazole, saquinavir, nelfinavir, indinavir, or atazanavir.

13. Concomitant therapy with CYP3A substate with narrow therapeutic window: cyclosporin, quinidine.

14. Concomitant therapy with CYP3A inducer; rifampin/rifampicin, phenytoin, carbamazepine.

15. Pregnancy or lactation

16. Active treatment for cancer.