Ticagrelor in Severe Community Acquired Pneumonia

Study Overview
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Brief Summary
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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.

Official Title
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Randomized Trial of Ticagrelor for Severe Community Acquired Pneumonia

Conditions
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Community Acquired Pneumonia, Severe

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: More than 72 hours have passed since meeting required inclusion criteria. Development of pneumonia after 72 hours of current hospitalization. Underlying disease likely to cause mortality within 90 days of randomization. A resident in a hospital, not nursing home, within 30 days prior to development of pneumonia. Patients who are moribund (not expected to live for more than 48 hours). No consent/inability to obtain consent from patient or surrogate. Patient's physician is unwilling to have patient enter the study. Age less than 50 years. Pregnancy. Breast feeding. Underlying immunodeficiency (e.g. HIV, neutropenia, active hematologic malignancy, functional or anatomical asplenia and hypogammaglobulinemia). 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). 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). Hepatic impairment a. Child Pugh score > 7 using data from outpatient setting Conditions that increase the risk of bleeding, e.g.: 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); A history of severe head trauma requiring hospitalization or intra-cranial surgery within 3 months; 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; Gastrointestinal bleeding within 6 weeks before the study unless a corrective procedure has been performed; Recent trauma considered to increase the risk of bleeding. Chronic renal disease requiring renal replacement therapy. Creatinine > 3 mg/dL. Platelet count < 50,000 /mm3. 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. Use of CYP3A inducers, e.g. rifampin, phenytoin, carbamazepine and phenobarbital. Simvastatin or Lovastatin doses > 40 mg per day. Digoxin use. Receiving aspirin and physician and/or patient unwilling to reduce aspirin dose to <100 mg per day. Daily Non-steroidal anti-inflammatory drugs (NSAID) use as an outpatient (other than Aspirin (ASA) as above). Sick Sinus Syndrome, 2nd or 3rd degree heart block, bradycardia induced syncope - unless pacemaker in place. Otherwise unsuitable for participation in the opinion of the investigator (i.e., homeless, non-compliant, etc.).

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticagrelor<br>Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days | Drug: Ticagrelor<br>* Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days<br>* Other names: Brilinta;|
| Placebo Comparator: Placebo<br>Placebo 180 mg loading dose followed by 90 mg BID for 90 days. | Drug: Placebo<br>* Placebo 180 mg loading dose followed by 90 mg BID for 90 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | death during 90 day study period | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shock Free Days | Not requiring pressor support for hypotension | 15 days | 
| Ventilator Free Days |  | 29 days | 
| In-hospital Mortality | Did the patient die during the hospitalization? | Throughout hospitalization (About 2 weeks) | 
| Hospital Free Days | Number of days the patient is not in the hospital | 29 days | 
| Stroke | Did the patient develop a stroke during the 90 day study? | 90 days | 
| Stroke, Myocardial Infarct, Mortality | number of participants that suffered stroke, myocardial infarct, mortality | 90 days | 
| Myocardial Infarction | Did the patient have a myocardial infarction during the 90 day study? | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAP, Pneumonia, Intensive Care Unit, Mechanical Ventilation