Ticagrelor in Severe Community Acquired Pneumonia
Condition: Community Acquired Pneumonia, Severe
MeSH terms: Pneumonia
Intervention: Ticagrelor; Placebo
Intervention description: Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days; Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Intervention MeSH terms: Ticagrelor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: CAP; Pneumonia; Intensive Care Unit; Mechanical Ventilation

Summary:

      The purpose of this study is to determine if the drug ticagrelor will be an effective
      treatment for patients with severe community acquired pneumonia. The primary objective is to
      reduce all-cause mortality in the ticagrelor group compared to the placebo group.
    

Eligibility criteria:

        Inclusion Criteria:

        1. Patients will have new "severe" CAP as defined by

        a. New (within 72 hours of hospital admission) radiographic finding consistent with
        pneumonia and admission or planned admission to an ICU for: i. Mechanical Ventilation
        (invasive or non-invasive) OR ii. Vasopressors (dobutamine and phosphodiesterase are not
        considered vasopressors for this criteria) OR iii. ICU admission due to severe respiratory
        distress or arterial desaturation. b. At least two of the following; i. recent increase in
        dyspnea ii. increased sputum production iii. change of character of sputum iv. White Blood
        Cells > 12,000 or < 4,000 cells/mm3 or >10% bands v. Body temperature >38ºC or <36ºC (any
        route)

        Exclusion Criteria:

          1. More than 72 hours have passed since meeting required inclusion criteria.

          2. Development of pneumonia after 72 hours of current hospitalization.

          3. Underlying disease likely to cause mortality within 90 days of randomization.

          4. A resident in a hospital, not nursing home, within 30 days prior to development of
             pneumonia.

          5. Patients who are moribund (not expected to live for more than 48 hours).

          6. No consent/inability to obtain consent from patient or surrogate.

          7. Patient's physician is unwilling to have patient enter the study.

          8. Age less than 50 years.

          9. Pregnancy.

         10. Breast feeding.

         11. Underlying immunodeficiency (e.g. HIV, neutropenia, active hematologic malignancy,
             functional or anatomical asplenia and hypogammaglobulinemia).

         12. Patient, surrogate, or physician not committed to full support (exception: a patient
             will not be excluded if he/she will receive all supportive care except for attempts at
             resuscitation from cardiac arrest).

         13. Unable to receive or unlikely to absorb enteral study drug (e.g., patients with
             partial or complete mechanical bowel obstruction, intestinal ischemia, infarction, and
             short bowel syndrome).

         14. Hepatic impairment

             a. Child Pugh score > 7 using data from outpatient setting

         15. Conditions that increase the risk of bleeding, e.g.:

               1. Surgery or the likely need for surgery during study, or evidence of active
                  bleeding postoperatively (ICU procedures such as line placement, tracheostomy and
                  chest tubes are not to be considered for this exclusion);

               2. A history of severe head trauma requiring hospitalization or intra-cranial
                  surgery within 3 months;

               3. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, or
                  mass lesions of the central nervous system, hemorrhagic stroke or intracranial
                  hemorrhage, or congenital bleeding diathesis;

               4. Gastrointestinal bleeding within 6 weeks before the study unless a corrective
                  procedure has been performed;

               5. Recent trauma considered to increase the risk of bleeding.

         16. Chronic renal disease requiring renal replacement therapy.

         17. Creatinine > 3 mg/dL.

         18. Platelet count < 50,000 /mm3.

         19. Use of a P2Y12 inhibitor within the 3 months prior to randomization or physician
             intent to initiate one of the CYP3A inhibitors, e.g. ketoconazole, itraconazole,
             voriconazole, clarithromycin, nefazodone, ritonavir, atazanovir, saquinavir,
             nelfinavir, indinavir, or telithromycin.

         20. Use of CYP3A inducers, e.g. rifampin, phenytoin, carbamazepine and phenobarbital.

         21. Simvastatin or Lovastatin doses > 40 mg per day.

         22. Digoxin use.

         23. Receiving aspirin and physician and/or patient unwilling to reduce aspirin dose to
             <100 mg per day.

         24. Daily Non-steroidal anti-inflammatory drugs (NSAID) use as an outpatient (other than
             Aspirin (ASA) as above).

         25. Sick Sinus Syndrome, 2nd or 3rd degree heart block, bradycardia induced syncope -
             unless pacemaker in place.

         26. Otherwise unsuitable for participation in the opinion of the investigator (i.e.,
             homeless, non-compliant, etc.).