This trial is active, not recruiting.

Condition community acquired pneumonia, severe
Treatments ticagrelor, placebo
Phase phase 2
Sponsor Gordon Bernard
Collaborator AstraZeneca
Start date August 2014
End date September 2016
Trial size 568 participants
Trial identifier NCT01998399, 131908


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days
ticagrelor Brilinta
Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days
(Placebo Comparator)
Placebo 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.

Primary Outcomes

All-cause mortality
time frame: 90 day

Secondary Outcomes

Shock free days
time frame: 14 days
Ventilator free days
time frame: 28 days
In-hospital mortality
time frame: Throughout hospitalization
Hospital free days
time frame: 60 days
time frame: 90 days
Composite endpoint: stroke, myocardial infarct, mortality
time frame: 90 days
Myocardial infarction
time frame: 90 days

Eligibility Criteria

Male or female participants at least 50 years old.

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.).

Additional Information

Official title Randomized Trial of Ticagrelor for Severe Community Acquired Pneumonia
Principal investigator Gordon R Bernard, MD
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Vanderbilt University.