Clinical trial NCT01998399: Ticagrelor in Severe Community Acquired Pneumonia
Official title: Randomized Trial of Ticagrelor for Severe Community Acquired Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Community Acquired Pneumonia, Severe
Keywords: CAP
Pneumonia
Intensive Care Unit
Mechanical Ventilation
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2013-11-28
Enrollment: 25
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.).

Primary outcomes:
measure: All-cause Mortality
timeFrame: 90 days
Secondary outcomes:
measure: Shock Free Days
timeFrame: 15 days
measure: Ventilator Free Days
timeFrame: 29 days
measure: In-hospital Mortality
timeFrame: Throughout hospitalization (About 2 weeks)
measure: Hospital Free Days
timeFrame: 29 days
measure: Stroke
timeFrame: 90 days
measure: Stroke, Myocardial Infarct, Mortality
timeFrame: 90 days
measure: Myocardial Infarction
timeFrame: 90 days
Other outcomes:
measure: Time to Initiation of Unassisted Breathing
timeFrame: 29 days
measure: Need for Re-instituting Assisted or Mechanical Ventilation After Achieving 48 Consecutive Hours of Unassisted Breathing or Comfort Care Chosen (Withdrawal of Support)
timeFrame: 90 days
measure: Need for Dialysis
timeFrame: 28 days
measure: ICU Length of Stay
timeFrame: 29 days
measure: Hospital Length of Stay
timeFrame: 29 days
measure: Discharge Disposition
timeFrame: 90 days
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Colorado Springs
country: United States
facility: University of Colorado
state: Colorado
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Atlanta
country: United States
facility: Atlanta VA Medical Center
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Springfield
country: United States
facility: Baystate Medical Center
state: Massachusetts
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Greensboro
country: United States
facility: Moses Cone
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Portland
country: United States
facility: Legacy Good Samaritan Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital - Texas Medical Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center San Antonio
state: Texas
city: Temple
country: United States
facility: Scott & White Memorial Hospital
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Vanderbilt University Medical Center
name: Gordon R Bernard, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Jon D Truwit, MD
role: PRINCIPAL_INVESTIGATOR
References: