Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor

NCT01883869 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 13-0374-F6A
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

The hypothesis to be tested is that ticagrelor (Brilinta™) will reduce platelet activation and markers of inflammation in patients with pneumonia.

Conditions

Pneumonia; Community Acquired Pneumonia; Hospital Acquired Pneumonia; Acute Lung Injury

Keywords

Platelet inhibition; Platelet-leukocyte aggregates; Platelet-neutrophil aggregates; CAP; HAP; ALI; Blood Platelets

Outcome Measures

Primary Outcomes (1)

• Platelet-Leukocyte Aggregates

  Platelet-leukocyte aggregates will be measured by flow cytometry.

  30 day

Secondary Outcomes (3)

• Platelet function tests

  30 day

• Systemic inflammation

  30 day

• Lung function

  During hospital stay up to 30 days.

Other Outcomes (5)

• Significant Bleeding Event

  30 days

• Mechanical Ventilation

  30 days

• Sepsis

  30 days

Study Arms (2)

ticagrelor

EXPERIMENTAL

180 mg orally once and then 90 mg orally daily for 7 days or until hospital discharge if sooner

Drug: ticagrelor

placebo

PLACEBO COMPARATOR

One loading dose and then daily for 7 days or until hospital discharge if sooner

Drug: placebo

Interventions

ticagrelor DRUG

Also known as: Brilinta

ticagrelor

placebo DRUG

placebo

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be 18 years of age or older
• Subjects must diagnosed with Community acquired pneumonia (CAP) or hospital acquired pneumonia (HAP) within 48 hours of diagnosis or presentation to hospital.
• Pneumonia will be defined as patients with a new radiographic finding(s) consistent with pneumonia and at least two of the following signs.
• Cough
• Fever: axillary temperature \>37.5ºC or tympanic temperature \>38.5ºC
• Hypothermia: axillary temperature \<34ºC or tympanic temperature \<35ºC.
• Purulent sputum production or respiratory secretion.
• Total peripheral white blood cell (WBC) count \>10,000/mm3; or \>15% band forms, regardless of total peripheral white count; or leucopenia with total WBC \< 4500/mm
• Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds, or egophony)
• Hypoxemia - defined as partial O2 pressure \<60mmHg while the patient was breathing normal air or a decrease in the partial O2 pressure of \>= 25% from an initial range.

You may not qualify if:

• Contraindication to ticagrelor (hypersensitivity or reaction to ticagrelor or another P2Y12 antagonist)
• Active bleeding or major bleeding history (e.g. intracranial bleeding)
• Clinically important anemia or thrombocytopenia (platelet count \<30)
• Surgery within 30 days or anticipated major surgery (Thoracic, Abdominal, Brain; placement of lines, tracheostomy, and chest tubes are not considered major).
• Oral anticoagulant therapy that cannot be stopped.
• Inability or unwillingness of treating physician to reduce dose of aspirin to 81mg.
• Fibrinolytic therapy in the last 24 hours.
• Increased risk of bradycardic events - 2nd or 3rd degree heart block, bradycardia induced syncope - unless pacemaker in place.
• Underlying immunodeficiency (HIV, neutropenia, receiving immunomodulating agents, active hematologic malignancy, functional or anatomical asplenia and hypogammaglobulinemia).
• Moderate or severe liver disease defined by Child Pugh score \>7 using data from outpatient setting or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 5 fold upper limits of normal.
• Renal dialysis
• Concomitant therapy with strong CYP3A inhibitors; ketoconazole, itraconazole, voriconazole, saquinavir, nelfinavir, indinavir, or atazanavir.
• Concomitant therapy with CYP3A substate with narrow therapeutic window: cyclosporin, quinidine.
• Concomitant therapy with CYP3A inducer; rifampin/rifampicin, phenytoin, carbamazepine.
• Pregnancy or lactation

Sponsors & Collaborators

• University of Kentucky: lead

Study Sites (2)

University of Kentucky Hospitals

Lexington, Kentucky, 40536, United States

Location

University of Kentucky Hospital

Lexington, Kentucky, 40536, United States

Location

Related Publications (1)

• Sexton TR, Zhang G, Macaulay TE, Callahan LA, Charnigo R, Vsevolozhskaya OA, Li Z, Smyth S. Ticagrelor Reduces Thromboinflammatory Markers in Patients With Pneumonia. JACC Basic Transl Sci. 2018 Aug 28;3(4):435-449. doi: 10.1016/j.jacbts.2018.05.005. eCollection 2018 Aug.

  PMID: 30175268 DERIVED

MeSH Terms

Conditions

Pneumonia; Community-Acquired Pneumonia; Healthcare-Associated Pneumonia; Acute Lung Injury

Interventions

Ticagrelor

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Community-Acquired Infections; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Injury

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Susan S Smyth, MD PhD

  University of Kentucky

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: May 1, 2013
• First Posted: June 21, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: September 13, 2018

Record last verified: 2018-09

Locations

US (2)