Coronary Artery DiseasePhase 4NCT02201394
Reversing Ticagrelor's Effects With Fresh Platelets
A Phase 4 study testing Ticagrelor loading dose, Aspirin loading dose and Ticagrelor maintenance dose in people with Coronary Artery Disease, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to shorten this period could be useful. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Coronary Artery Disease
- What is being tested?
- Ticagrelor loading dose, Aspirin loading dose and Ticagrelor maintenance dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Jun 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female volunteer between 18 and 75 years old.
- History of stable (i.e. non-acute) cardiovascular disease or the presence of risk factors for cardiovascular disease (i.e. hypertension, diabetes, hyperlipidemia, high calcium score and abnormal findings on angiography or stress test).
Who cannot join
- Conditions associated with hemorrhagic risk, e.g., frequent epistaxis, gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.
- Allergy or hypersensitivity to aspirin or ticagrelor.
- Loss of >400 mL blood or blood donation within past 3 months.
- Positive serology for hepatitis B (HBs Ag) or hepatitis C.
- History of drug abuse or alcohol abuse.
- Positive pregnancy test.
- Evidence of unstable or acute cardiovascular disease (e.g., unstable angina, recent myocardial infarction, congestive heart failure).
- History of clinically relevant pulmonary, hepatic, gastrointestinal, renal, metabolic, hematologic, neurologic, respiratory or psychiatric disease, bleeding, acute infectious disease or signs of acute illness.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Normalizing Platelet Reactivity After Treatment With Ticagrelor
Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to shorten this period could be useful. The present study aims to investigate the possibility of reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets. Fresh platelets will be added to blood samples of treated patients in varying concentrations at specific timepoints to determine the time and amount of fresh platelets needed to normalize platelet reactivity in the treated samples.
Read the detailed description
The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS patients at risk for further cardiovascular events. Any means to shorten this vulnerable period would be of critical value. One possibility to speed up the recovery of the inhibited platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are frequently administered to patients during surgery who had received prior antiplatelet therapy. However, the degree to which these transfusions restore platelet function in the recipient subjects' blood and the time from dosing when they are most effective are unknown. The timing is critical in scenarios where urgent surgery is required because infusion of platelets too soon after antiplatelet dosing could render them useless by the residual drug in circulation.
The aim of the present study is to investigate the restoration of platelet function of ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2 arms mimicking different clinical scenarios:
- Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be given to study subjects and platelet testing will be performed after addition of fresh platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and 48-hours post-dose, to assess the time required for normalizing subject's platelet function after a LD of ticagrelor.
- Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once daily) for 3-7 days. After the last dose, platelet testing will be performed after addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours post-dose to assess the time required for normalizing subject's platelet function after daily treatment with ticagrelor.
Platelet testing will be carried out using the following methodologies:
- Platelet Aggregation - VerifyNow P2Y12 assay.
- Platelet Aggregation - Multiplate Analyzer.
- Conditions
- Coronary Artery Disease
- Being tested
- Ticagrelor loading dose, Aspirin loading dose, Ticagrelor maintenance dose, Aspirin maintenance dose
- Keywords
- Antiplatelet, Ticagrelor, Platelets, Thrombosis, Coronary artery disease
- Medical subject headings
- Coronary Artery Disease, Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor loading doseDrug
Also called Brilinta
Single loading dose of Ticagrelor 180 mg
Aspirin loading doseDrug
Also called Acetylsalicylic acid, ASA
Single loading dose of Aspirin 325 mg
Ticagrelor maintenance doseDrug
Also called Ticagrelor, Brilinta
Ticagrelor 90 mg twice daily x 7 days
Aspirin maintenance doseDrug
Also called Aspirin, ASA
Aspirin 81 mg once daily x 7 days
| Study group | Role | What they receive |
|---|---|---|
| Loading dose | Experimental | Patients with stable CVD given a single ticagrelor loading dose and aspirin loading dose Receives: Drug: Ticagrelor loading dose; Drug: Aspirin loading dose |
| Maintenance dose | Experimental | Patients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week. Receives: Drug: Ticagrelor maintenance dose; Drug: Aspirin maintenance dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
P2Y12 Reaction Unit (PRU)
Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.
Measured: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose
Platelet Aggregation Using Multiplate Analyzer
Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.
Measured: Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Juan J Badimon, Icahn School of Medicine at Mount Sinai
- Investigators
- Juan J Badimon, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201394
- Sponsor's protocol ID
- GCO 13-1802
- Status last verified
- Oct 2017
- First submitted
- 24 Jul 2014
- Last updated
- 5 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Zafar MU, Smith DA, Baber U, Sartori S, Chen K, Lam DW, Linares-Koloffon CA, Rey-Mendoza J, Jimenez Britez G, Escolar G, Fuster V, Badimon JJ. Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor. Circ Cardiovasc Interv. 2017 Aug;10(8):e005120. doi: 10.1161/CIRCINTERVENTIONS.117.005120.
PubMed 28768756
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Normalizing Platelet Reactivity After Treatment With Ticagrelor
- ClinicalTrials.gov ID
- NCT02201394
- Acronym / sponsor ID
- GCO 13-1802
- Conditions
- Coronary Artery Disease
- Keywords
- Antiplatelet, Ticagrelor, Platelets, Thrombosis, Coronary artery disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jul 2014
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 28 Jul 2014 (estimated)
- Results
- Posted 5 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute coronary syndrome (ACS) patients treated with antiplatelet drugs who require coronary artery bypass grafting (CABG) surgery have to wait 5-7 days for the effects of the drugs to wean off. This treatment-devoid period leaves the patient vulnerable, therefore any means to shorten this period could be useful. The present study aims to investigate the possibility of reversing the antiplatelet effects of ticagrelor with the help of fresh donor platelets. Fresh platelets will be added to blood samples of treated patients in varying concentrations at specific timepoints to determine the time and amount of fresh platelets needed to normalize platelet reactivity in the treated samples.
Detailed description
The current American College of Cardiology/American Heart Association (ACC/AHA) guidelines for ACS patients requiring CABG surgery after treatment with dual antiplatelet therapy recommend delaying surgery for 5-7 days after discontinuation of therapy, to allow for the dissipation of its antiplatelet effects. This treatment-devoid waiting period puts the ACS patients at risk for further cardiovascular events. Any means to shorten this vulnerable period would be of critical value. One possibility to speed up the recovery of the inhibited platelets is to administer infusions of fresh platelets. In fact, platelet transfusions are frequently administered to patients during surgery who had received prior antiplatelet therapy. However, the degree to which these transfusions restore platelet function in the recipient subjects' blood and the time from dosing when they are most effective are unknown. The timing is critical in scenarios where urgent surgery is required because infusion of platelets too soon after antiplatelet dosing could render them useless by the residual drug in circulation.
The aim of the present study is to investigate the restoration of platelet function of ticagrelor-treated subjects by adding donor platelets to their blood. The study would have 2 arms mimicking different clinical scenarios:
- Clinical Scenario 1 - Patient given a loading dose (LD) of ticagrelor in the emergency room, requires surgery: A single LD of ticagrelor (180 mg) with aspirin (325 mg) will be given to study subjects and platelet testing will be performed after addition of fresh platelets to their blood ex vivo. Donor platelets will be added at 4-, 6-, 24- and 48-hours post-dose, to assess the time required for normalizing subject's platelet function after a LD of ticagrelor.
- Clinical Scenario 2 - Patient on maintenance dosing (MD) of ticagrelor, requires surgery: Subjects will receive ticagrelor (90 mg twice daily) with aspirin (81 mg once daily) for 3-7 days. After the last dose, platelet testing will be performed after addition of fresh platelets to their blood ex vivo, at 4-, 6-, 24- and 48-hours post-dose to assess the time required for normalizing subject's platelet function after daily treatment with ticagrelor.
Platelet testing will be carried out using the following methodologies:
- Platelet Aggregation - VerifyNow P2Y12 assay.
- Platelet Aggregation - Multiplate Analyzer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Loading dose | Experimental | Drug: Ticagrelor loading dose, Drug: Aspirin loading dosePatients with stable CVD given a single ticagrelor loading dose and aspirin loading dose |
| Maintenance dose | Experimental | Drug: Ticagrelor maintenance dose, Drug: Aspirin maintenance dosePatients with stable CVD given ticagrelor maintenance dose and aspirin maintenance dose for one week. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male or female volunteer between 18 and 75 years old.
- History of stable (i.e. non-acute) cardiovascular disease or the presence of risk factors for cardiovascular disease (i.e. hypertension, diabetes, hyperlipidemia, high calcium score and abnormal findings on angiography or stress test).
Key exclusion criteria (8 listed)
- Conditions associated with hemorrhagic risk, e.g., frequent epistaxis, gastrointestinal ulcer, hemorrhagic vascular lesions, recent surgery.
- Allergy or hypersensitivity to aspirin or ticagrelor.
- Loss of >400 mL blood or blood donation within past 3 months.
- Positive serology for hepatitis B (HBs Ag) or hepatitis C.
- History of drug abuse or alcohol abuse.
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 |
|---|---|---|
| Ticagrelor loading doseAlso: BrilintaSingle loading dose of Ticagrelor 180 mg | Drug | Loading dose |
| Aspirin loading doseAlso: Acetylsalicylic acid, ASASingle loading dose of Aspirin 325 mg | Drug | Loading dose |
| Ticagrelor maintenance doseAlso: Ticagrelor, BrilintaTicagrelor 90 mg twice daily x 7 days | Drug | Maintenance dose |
| Aspirin maintenance doseAlso: Aspirin, ASAAspirin 81 mg once daily x 7 days | Drug | Maintenance dose |
Primary outcome
P2Y12 Reaction Unit (PRU)
Time frame: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose
Platelet function normalization using different concentrations (0%, 25%, 50%, and 75% supplementations) of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using VerifyNow and expressed as P2Y12 Reaction Unit (PRU). The P2Y12 reaction unit (PRU) is an arbitrary unit of measure that represents the amount of platelet aggregation specific to the P2Y12 receptor.
Platelet Aggregation Using Multiplate Analyzer
Time frame: Baseline (pre-treatment), 4, 6, 24, and 48 hours post Loading dose/last Maintenance dose
Platelet function normalization using different concentrations of fresh platelet within 48 hours of Ticagrelor Loading dose/last Maintenance dose, assessed using Multiplate Aggregometry (ADPtest), results expressed as Area Under Curve (U), where 1 U = 10 AU * min.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28768756Zafar MU, Smith DA, Baber U, Sartori S, Chen K, Lam DW, Linares-Koloffon CA, Rey-Mendoza J, Jimenez Britez G, Escolar G, Fuster V, Badimon JJ. Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor. Circ Cardiovasc Interv. 2017 Aug;10(8):e005120. doi: 10.1161/CIRCINTERVENTIONS.117.005120.
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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.
Juan J Badimon, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ticagrelor loading dose, Aspirin loading dose and Ticagrelor maintenance dose in people with Coronary Artery Disease, run by Icahn School of Medicine at Mount Sinai at 1 site 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 2 inclusion and 8 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 5 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
P2Y12 Reaction Unit (PRU) (time frame: Baseline (pre-treatment), 4, 6, 24 and 48 hours post Loading dose/last Maintenance dose). The study lists 2 primary outcomes in all. 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 NCT02201394, 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 5 Dec 2017.