Ticagrelor in Severe Community Acquired Pneumonia (TCAP)

Randomized Trial of Ticagrelor for Severe Community Acquired Pneumonia

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.

Study Overview

• Status: Terminated
• Conditions: Community Acquired Pneumonia, Severe
• Intervention / Treatment: Drug: Ticagrelor; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • University of Colorado
    • Denver, Colorado, United States, 80204
      • Denver Health
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • Atlanta VA Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Springfield, Massachusetts, United States, 01199
      • Baystate Medical Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Moses Cone
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Good Samaritan Medical Center
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital - Texas Medical Center
    • Houston, Texas, United States, 77030
      • Baylor
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio
    • San Antonio, Texas, United States, 78229
      • South Texas Veterans Health Care System
    • Temple, Texas, United States, 76508
      • Scott & White Memorial Hospital
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days	Drug: Ticagrelor; Ticagrelor 180 mg loading dose followed by 90 mg BID for 90 days; Other Names: Brilinta
Placebo Comparator: Placebo; Placebo 180 mg loading dose followed by 90 mg BID for 90 days.	Drug: Placebo; Placebo 180 mg loading dose followed by 90 mg BID for 90 days.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Initiation of Unassisted Breathing	Only in patients on mechanical ventilation and assuming patient achieves 48 consecutive hours of unassisted breathing	29 days
Need for Re-instituting Assisted or Mechanical Ventilation After Achieving 48 Consecutive Hours of Unassisted Breathing or Comfort Care Chosen (Withdrawal of Support)		90 days
Need for Dialysis		28 days
ICU Length of Stay	Includes ICU readmission if during same hospital stay	29 days
Hospital Length of Stay	In days	29 days
Discharge Disposition	(Home, other facility, with or without assisted ventilation)	90 days

Collaborators and Investigators

• Sponsor: Gordon Bernard
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Gordon R Bernard, MD, Vanderbilt University Medical Center; Principal Investigator: Jon D Truwit, MD, Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: November 15, 2013
• First Submitted That Met QC Criteria: November 23, 2013
• First Posted (Estimate): November 28, 2013

Study Record Updates

• Last Update Posted (Actual): December 11, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Pneumonia; Intensive Care Unit; Mechanical Ventilation; CAP
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Pneumonia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor
• Other Study ID Numbers: 131908 (Other Identifier: Rutgers, The State University of New Jersey)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO