Ticagrelor in Severe Community Acquired Pneumonia

Phase 2

Terminated

• Conditions: Community Acquired Pneumonia, Severe
• Interventions: Drug: Placebo; Drug: Ticagrelor

• Registration Number: NCT01998399
• Lead Sponsor: Gordon Bernard

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-15
• Study First Submitted QC: 2013-11-23
• Study First Posted: 2013-11-28
• Study Start: 2014-08
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Results First Submitted: 2016-01-08
• Results First Submitted QC: 2016-02-12
• Results First Posted: 2016-03-11
• Status Verified: 2017-11
• Last Update Submitted: 2017-11-07
• Last Update Posted: 2017-12-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

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.).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo 180 mg loading dose followed by 90 mg BID for 90 days.
Ticagrelor	Ticagrelor	Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days

Primary Outcome Measures

Name	Time	Method
All-cause Mortality	90 days	death during 90 day study period

Secondary Outcome Measures

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

Trial Locations

Locations (26)

Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

University of Virginia; 🇺🇸 Charlottesville, Virginia, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

The Ohio State University; 🇺🇸 Columbus, Ohio, United States

Oregon Health Sciences University; 🇺🇸 Portland, Oregon, United States

Scott & White Memorial Hospital; 🇺🇸 Temple, Texas, United States

Denver Health; 🇺🇸 Denver, Colorado, United States

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

Atlanta VA Medical Center; 🇺🇸 Atlanta, Georgia, United States

University of Colorado; 🇺🇸 Colorado Springs, Colorado, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

University of Arizona; 🇺🇸 Tucson, Arizona, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Memorial Hermann Hospital - Texas Medical Center; 🇺🇸 Houston, Texas, United States

Baylor; 🇺🇸 Houston, Texas, United States

South Texas Veterans Health Care System; 🇺🇸 San Antonio, Texas, United States

University of Texas Health Science Center San Antonio; 🇺🇸 San Antonio, Texas, United States

University of Utah; 🇺🇸 Salt Lake City, Utah, United States

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Moses Cone; 🇺🇸 Greensboro, North Carolina, United States

Regions Hospital; 🇺🇸 Saint Paul, Minnesota, United States

Legacy Emanuel Medical Center; 🇺🇸 Portland, Oregon, United States

Legacy Good Samaritan Medical Center; 🇺🇸 Portland, Oregon, United States

Intermountain Medical Center; 🇺🇸 Murray, Utah, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States