PneumoniaPhase 1XANTHIPPENCT01883869
Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor
A Phase 1 study testing ticagrelor in people with Pneumonia and Community Acquired Pneumonia, run by University of Kentucky at 2 sites in United States.
Trial summary
The hypothesis to be tested is that ticagrelor (Brilinta™) will reduce platelet activation and markers of inflammation in patients with pneumonia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pneumonia, Community Acquired Pneumonia, Hospital Acquired Pneumonia
- What is being tested?
- ticagrelor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2013to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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
- Active treatment for cancer.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Kentucky Hospitals
Lexington, Kentucky, 40536
University of Kentucky Hospital
Lexington, Kentucky, 40536
About this study
Official title: XANTHIPPE: Examining the Effect of Ticagrelor on Platelet Activation, Platelet-Leukocyte Aggregates, and Acute Lung Injury in Pneumonia
The hypothesis to be tested is that ticagrelor (Brilinta™) will reduce platelet activation and markers of inflammation in patients with pneumonia.
Read the detailed description
While it is well established that platelets are integral to hemostasis, more recent evidence points to an important role for platelets in inflammation and immunity. Platelet activation and sequestration in pulmonary tissue is a key feature in inflammatory or infectious states such as sepsis and acute respiratory distress syndrome (ARDS). Platelets may mediate acute lung injury (ALI) by recruiting neutrophils, triggering neutrophil extracellular DNA nets, and releasing granule contents and microparticles. Anti-platelet therapy in this setting may prevent platelet activation, platelet - leukocyte aggregate formation, and inflammation.
The objective of this pilot study is to determine if ticagrelor therapy in individuals with pneumonia reduces markers of platelet activation, platelet-leukocyte aggregates, inflammation, acute lung injury, and lung mechanics. Because the benefit of anti-platelet therapy may the greatest in patients with more significant lung injury, the investigators will enroll patients with community-acquired pneumonia (CAP) requiring hospitalization or patients with hospital acquired pneumonia (HAP) within 48 hours of diagnosis. On study day 1, subjects will be randomized to receive ticagrelor (180 mg load and 90 mg BID) or placebo. Study medication (ticagrelor or placebo) will be administered twice daily on days 2 - 7 or until hospital discharge, if sooner than 7 days. Blood will be collected and assays performed on day 1 prior to study medication administration (baseline), day 2, 3, 7, day of discharge (if before 7 days), and 30 days for analysis of platelet count, markers of platelet activation, platelet - leukocyte interactions, biomarkers of inflammation, and measurements of lung mechanics.
- Being tested
- ticagrelor, placebo
- Keywords
- Platelet inhibition, Platelet-leukocyte aggregates, Platelet-neutrophil aggregates, CAP, HAP, ALI, Blood Platelets
- Medical subject headings
- Pneumonia, Community-Acquired Pneumonia, Healthcare-Associated Pneumonia, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ticagrelorDrug
Also called Brilinta
placeboDrug
placebo
| Study group | Role | What they receive |
|---|---|---|
| ticagrelor | Experimental | 180 mg orally once and then 90 mg orally daily for 7 days or until hospital discharge if sooner Receives: Drug: ticagrelor |
| placebo | Placebo comparator | One loading dose and then daily for 7 days or until hospital discharge if sooner Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Platelet-Leukocyte Aggregates
Platelet-leukocyte aggregates will be measured by flow cytometry.
Measured: 30 day
Secondary outcomes (3)
Platelet function tests
Platelet function will be monitored by aggregation and by measuring markers of platelet secretion
Measured: 30 day
Systemic inflammation
Markers of inflammation will be measured in plasma or serum
Measured: 30 day
Lung function
In non-ventilated patients, spirometry, maximal voluntary ventilation, maximal inspiratory and expiratory pressure generation, and P/F ratio (PaO2/FiO2)
In ventilated patients, respiratory system static compliance, airway resistance, oxygenation index (PaO2/FiO2), and maximal inspiratory and expiratory pressure generation.
Measured: During hospital stay up to 30 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kentucky
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Susan Smyth, University of Kentucky
- Investigators
- Susan S Smyth, MD PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01883869
- Sponsor's protocol ID
- 13-0374-F6A
- Acronym
- XANTHIPPE
- Status last verified
- Sep 2018
- First submitted
- 1 May 2013
- Last updated
- 13 Sep 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30175268
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- XANTHIPPE: Examining the Effect of Ticagrelor on Platelet Activation, Platelet-Leukocyte Aggregates, and Acute Lung Injury in Pneumonia
- ClinicalTrials.gov ID
- NCT01883869
- Acronym / sponsor ID
- XANTHIPPE / 13-0374-F6A
- Keywords
- Platelet inhibition, Platelet-leukocyte aggregates, Platelet-neutrophil aggregates, CAP, HAP, ALI, Blood Platelets
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- University of KentuckyUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 21 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis to be tested is that ticagrelor (Brilinta™) will reduce platelet activation and markers of inflammation in patients with pneumonia.
Detailed description
While it is well established that platelets are integral to hemostasis, more recent evidence points to an important role for platelets in inflammation and immunity. Platelet activation and sequestration in pulmonary tissue is a key feature in inflammatory or infectious states such as sepsis and acute respiratory distress syndrome (ARDS). Platelets may mediate acute lung injury (ALI) by recruiting neutrophils, triggering neutrophil extracellular DNA nets, and releasing granule contents and microparticles. Anti-platelet therapy in this setting may prevent platelet activation, platelet - leukocyte aggregate formation, and inflammation.
The objective of this pilot study is to determine if ticagrelor therapy in individuals with pneumonia reduces markers of platelet activation, platelet-leukocyte aggregates, inflammation, acute lung injury, and lung mechanics. Because the benefit of anti-platelet therapy may the greatest in patients with more significant lung injury, the investigators will enroll patients with community-acquired pneumonia (CAP) requiring hospitalization or patients with hospital acquired pneumonia (HAP) within 48 hours of diagnosis. On study day 1, subjects will be randomized to receive ticagrelor (180 mg load and 90 mg BID) or placebo. Study medication (ticagrelor or placebo) will be administered twice daily on days 2 - 7 or until hospital discharge, if sooner than 7 days. Blood will be collected and assays performed on day 1 prior to study medication administration (baseline), day 2, 3, 7, day of discharge (if before 7 days), and 30 days for analysis of platelet count, markers of platelet activation, platelet - leukocyte interactions, biomarkers of inflammation, and measurements of lung mechanics.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ticagrelor | Experimental | Drug: ticagrelor180 mg orally once and then 90 mg orally daily for 7 days or until hospital discharge if sooner |
| placebo | Placebo comparator | Drug: placeboOne loading dose and then daily for 7 days or until hospital discharge if sooner |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ticagrelorAlso: Brilinta | Drug | ticagrelor |
| placeboplacebo | Drug | placebo |
Primary outcome
Platelet-Leukocyte Aggregates
Time frame: 30 day
Platelet-leukocyte aggregates will be measured by flow cytometry.
3 secondary outcomes
Platelet function tests
Time frame: 30 day
Systemic inflammation
Time frame: 30 day
Lung function
Time frame: During hospital stay up to 30 days.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2018.
- Derived from this study: PubMed 30175268Sexton 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan S Smyth, MD PhD principal investigator
University of Kentucky
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ticagrelor in people with Pneumonia and Community Acquired Pneumonia, run by University of Kentucky at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Platelet-Leukocyte Aggregates (time frame: 30 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01883869, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.