Atrial FibrillationPhase 1NCT02080858
Triple vs. Dual Therapy
A Phase 1 study testing Ticagrelor + Apixaban + ASA and Ticagrelor + Apixaban in people with Atrial Fibrillation and Acute Coronary Syndrome, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Background: The acute coronary syndrome (ACS) is a complication of coronary artery disease (CAD) and associated with increased mortality. Dual antiplatelet therapy of acetylsalicylic acid (ASA) with P2Y12 receptor antagonists such as clopidogrel is a cornerstone in the treatment of patients with advanced CAD. Read more about this study
- Who is it for?
- Ages 18 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Atrial Fibrillation, Acute Coronary Syndrome
- What is being tested?
- Ticagrelor + Apixaban + ASA and Ticagrelor + Apixaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteAustria
- Study dates
- May 2014to Feb 2015
- 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 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy male subjects; 18 - 40 years of age
- body mass index between 18 and 27 kg/m2
- Written informed consent
- Normal findings in medical \& bleeding history
- Non-smoking behaviour
Who cannot join
- Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
- Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease)
- Known disorders with increased bleeding risk (e.g. peridontitis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer)
- Known sensitivity to common causes of bleeding (e.g. nasal)
- History of thromboembolism
- Anaemia (defined as haemoglobin levels < LLN)
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- Impaired liver function (AST, ALT, GGT >2 x ULN, Bilirubin >1.5 x ULN)
- Impaired renal function (serum creatinine > 1.3 mg/dl)
- Any other relevant deviation from the normal range in clinical chemistry, haematology or urine analysis
- HIV-1/2-Ab, HbsAg or HCV-Ab positive serology
- Systolic blood pressure above 145 mmHg, diastolic blood pressure above 95 mmHg
- Known allergy against test agents
- Regular daily consumption of more than on litre of xanthine-containing beverages or more than 40g alcohol
- Participation in another clinical trial during the preceding 3 weeks
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Vienna, Department of Clinical Pharmacology
Vienna, State of Vienna, 1090
About this study
Official title: The Effect of Ticagrelor and Apixaban With or Without Acetylsalicylic Acid on Markers of Coagulation Activation at the Site of Thrombus Formation in Vivo in Healthy Male Subjects and in an ex Vivo Perfusion Chamber Model at High and Low Shear Rate
Background:
The acute coronary syndrome (ACS) is a complication of coronary artery disease (CAD) and associated with increased mortality. Dual antiplatelet therapy of acetylsalicylic acid (ASA) with P2Y12 receptor antagonists such as clopidogrel is a cornerstone in the treatment of patients with advanced CAD. Due to delayed onset of action, intersubject variability or resistance to clopidogrel, different platelet aggregation inhibitors have been developed. Ticagrelor is a reversible P2Y12 receptor antagonist with superior efficacy compared to clopidogrel in the prevention of cardiovascular death in these patients.
Read more
Atrial fibrillation (AF) is also associated with thromboembolic events and substantial mortality. Beside vitamin K antagonists (VKA, phenprocoumon) for stroke prevention in patients with AF, the direct factor Xa inhibitor apixaban has recently received approval for prophylactic treatment of patients with non-valvular AF.
However, there is a lack of efficacy or safety data for the combined impact of antithrombotic drugs in patients requiring arterial and venous thromboembolic prophylaxis due to their underlying co-morbidities. One trial suggests treatment with VKA + clopidogrel without ASA as equal effective as antithrombotic triple therapy (with ASA) in this population. However, the effect in combination with novel oral anticoagulants has not been investigated so far.
Study objectives:
To evaluate the effect of ticagrelor + apixaban in combination with or without ASA at steady state on markers of coagulation activation and on thrombus size in an ex vivo perfusion chamber experiment. Additionally, plasma samples will be analysed for PK-data (ticagrelor \& apixaban concentrations)
Study design:
A single-centre, prospective, sequential, controlled, analyst-blinded study in two groups. Subjects will receive ticagrelor + apixaban in combination with (study A) or without (study B) ASA. All IMPs will be administered at doses indicated for stroke prevention in AF (lower dose: 2.5mg due to ethical concerns) or ACS. Markers on thrombin generation and platelet activation will be studied in venous blood where coagulation is in resting state and in shed blood where the clotting system is activated in the microvasculature in vivo: prothrombin fragment 1+2 (F1+2), thrombin-anti-thrombin (TAT), β-thromboglobulin (β-TG). Additionally, inhibition of factor Xa activity and concentrations of ticagrelor and apixaban will be assessed in venous blood. Further, thrombus size of clots formed in an ex vivo perfusion chamber will be determined by measurement of D-Dimer and p-Selectin levels.
Study population A total of 40 healthy, non-smoking and drug-free male volunteers will be enrolled (study A and B; n = 20 per group).
Main outcome variables:
- β-TG in shed blood
Additional outcome variables:
- F1+2 and TAT in shed blood
- fibrin formation (D-Dimer) and platelet deposition (p-Selectin) in an ex vivo perfusion chamber model of thrombosis
- β-TG, F1+2, TAT \& inhibition of factor Xa in venous blood
- PT, aPTT and ACT in venous blood
- ticagrelor \& apixaban plasma concentrations
- shed blood volume
- Conditions
- Atrial Fibrillation, Acute Coronary Syndrome
- Being tested
- Ticagrelor + Apixaban + ASA, Ticagrelor + Apixaban
- Keywords
- Apixaban, Ticagrelor, ASA, shed blood, perfusion chamber
- Medical subject headings
- Atrial Fibrillation, Acute Coronary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ticagrelor + Apixaban + ASADrug
Ticagrelor + ApixabanDrug
| Study group | Role | What they receive |
|---|---|---|
| Ticagrelor + Apixaban + ASA | Experimental | 180 mg Ticagrelor loading dose + apixaban 2.5 mg bid + 300 mg ASA loading dose (day 1) followed by ticagrelor 90 mg bid + apixaban 2.5 mg + 100 mg ASA od to reach steady state conditions within 4.5 days Receives: Drug: Ticagrelor + Apixaban + ASA |
| Ticagrelor + Apixaban | Active comparator | 180mg ticagrelor loading dose + apixaban 2.5 mg bid (day 1) followed by ticagrelor 90 mg bid + apixaban 2.5 mg to reach steady state conditions within 4.5 days Receives: Drug: Ticagrelor + Apixaban |
What is being measured
The primary outcome is the main question the study is designed to answer.
β-thromboglobulin (β-TG)
Of primary interest is the difference in shed blood β-TG "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
Measured: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
Secondary outcomes (4)
Prothrombin fragment F1+2 (F1+2)
Of primary interest is the difference in shed blood F1+2 "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
Measured: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
Thrombin-Anti-Thrombin (TAT)
Of primary interest is the difference of TAT in shed blood "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
Measured: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
D-dimer
Changes on fibrin formation in an ex vivo perfusion chamber model of thrombosis at high and low shear rate. Of primary interest is the difference in D-Dimer "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
Measured: Changes from baseline, at 3 hours, at trough and peak steady state conditions
P-selectin
Changes on platelet deposition in an ex vivo perfusion chamber model of thrombosis at high and low shear rate. Of primary interest is the difference in D-Dimer "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
Measured: Changes from baseline, at 3 hours, at trough and peak steady state conditions
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2014 (estimated)
- Study startMay 2014
- Primary completionOct 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Michael Wolzt, Prof. MD, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02080858
- Sponsor's protocol ID
- TVDAT-1.0
- Status last verified
- Apr 2015
- First submitted
- 5 Mar 2014
- Last updated
- 7 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Ticagrelor and Apixaban With or Without Acetylsalicylic Acid on Markers of Coagulation Activation at the Site of Thrombus Formation in Vivo in Healthy Male Subjects and in an ex Vivo Perfusion Chamber Model at High and Low Shear Rate
- ClinicalTrials.gov ID
- NCT02080858
- Acronym / sponsor ID
- TVDAT-1.0
- Conditions
- Atrial Fibrillation, Acute Coronary Syndrome
- Keywords
- Apixaban, Ticagrelor, ASA, shed blood, perfusion chamber
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- Oct 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 6 Mar 2014 (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.
Background:
The acute coronary syndrome (ACS) is a complication of coronary artery disease (CAD) and associated with increased mortality. Dual antiplatelet therapy of acetylsalicylic acid (ASA) with P2Y12 receptor antagonists such as clopidogrel is a cornerstone in the treatment of patients with advanced CAD. Due to delayed onset of action, intersubject variability or resistance to clopidogrel, different platelet aggregation inhibitors have been developed. Ticagrelor is a reversible P2Y12 receptor antagonist with superior efficacy compared to clopidogrel in the prevention of cardiovascular death in these patients.
Atrial fibrillation (AF) is also associated with thromboembolic events and substantial mortality. Beside vitamin K antagonists (VKA, phenprocoumon) for stroke prevention in patients with AF, the direct factor Xa inhibitor apixaban has recently received approval for prophylactic treatment of patients with non-valvular AF.
However, there is a lack of efficacy or safety data for the combined impact of antithrombotic drugs in patients requiring arterial and venous thromboembolic prophylaxis due to their underlying co-morbidities. One trial suggests treatment with VKA + clopidogrel without ASA as equal effective as antithrombotic triple therapy (with ASA) in this population. However, the effect in combination with novel oral anticoagulants has not been investigated so far.
Study objectives:
To evaluate the effect of ticagrelor + apixaban in combination with or without ASA at steady state on markers of coagulation activation and on thrombus size in an ex vivo perfusion chamber experiment. Additionally, plasma samples will be analysed for PK-data (ticagrelor \& apixaban concentrations)
Study design:
A single-centre, prospective, sequential, controlled, analyst-blinded study in two groups. Subjects will receive ticagrelor + apixaban in combination with (study A) or without (study B) ASA. All IMPs will be administered at doses indicated for stroke prevention in AF (lower dose: 2.5mg due to ethical concerns) or ACS. Markers on thrombin generation and platelet activation will be studied in venous blood where coagulation is in resting state and in shed blood where the clotting system is activated in the microvasculature in vivo: prothrombin fragment 1+2 (F1+2), thrombin-anti-thrombin (TAT), β-thromboglobulin (β-TG). Additionally, inhibition of factor Xa activity and concentrations of ticagrelor and apixaban will be assessed in venous blood. Further, thrombus size of clots formed in an ex vivo perfusion chamber will be determined by measurement of D-Dimer and p-Selectin levels.
Study population A total of 40 healthy, non-smoking and drug-free male volunteers will be enrolled (study A and B; n = 20 per group).
Main outcome variables:
- β-TG in shed blood
Additional outcome variables:
- F1+2 and TAT in shed blood
- fibrin formation (D-Dimer) and platelet deposition (p-Selectin) in an ex vivo perfusion chamber model of thrombosis
- β-TG, F1+2, TAT \& inhibition of factor Xa in venous blood
- PT, aPTT and ACT in venous blood
- ticagrelor \& apixaban plasma concentrations
- shed blood volume
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ticagrelor + Apixaban + ASA | Experimental | Drug: Ticagrelor + Apixaban + ASA180 mg Ticagrelor loading dose + apixaban 2.5 mg bid + 300 mg ASA loading dose (day 1) followed by ticagrelor 90 mg bid + apixaban 2.5 mg + 100 mg ASA od to reach steady state conditions within 4.5 days |
| Ticagrelor + Apixaban | Active comparator | Drug: Ticagrelor + Apixaban180mg ticagrelor loading dose + apixaban 2.5 mg bid (day 1) followed by ticagrelor 90 mg bid + apixaban 2.5 mg to reach steady state conditions within 4.5 days |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Healthy male subjects; 18 - 40 years of age
- body mass index between 18 and 27 kg/m2
- Written informed consent
- Normal findings in medical \& bleeding history
- Non-smoking behaviour
Key exclusion criteria (14 listed)
- Regular intake of any medication including OTC drugs and herbals within 2 weeks before IMP administration
- Known coagulation disorders (e.g. haemophilia, von Willebrand´s disease)
- Known disorders with increased bleeding risk (e.g. peridontitis, haemorrhoids, acute gastritis, peptic ulcer, intestinal ulcer)
- Known sensitivity to common causes of bleeding (e.g. nasal)
- History of thromboembolism
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 + Apixaban + ASA | Drug | Ticagrelor + Apixaban + ASA |
| Ticagrelor + Apixaban | Drug | Ticagrelor + Apixaban |
Primary outcome
β-thromboglobulin (β-TG)
Time frame: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
Of primary interest is the difference in shed blood β-TG "3h post-dose at steady state (peak)" or "pre-dose at steady state (trough)" and Baseline during triple therapy vs. dual therapy.
4 secondary outcomes
Prothrombin fragment F1+2 (F1+2)
Time frame: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
Thrombin-Anti-Thrombin (TAT)
Time frame: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions
D-dimer
Time frame: Changes from baseline, at 3 hours, at trough and peak steady state conditions
P-selectin
Time frame: Changes from baseline, at 3 hours, at trough and peak steady state conditions
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 7 Apr 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 + Apixaban + ASA and Ticagrelor + Apixaban in people with Atrial Fibrillation and Acute Coronary Syndrome, run by Medical University of Vienna at 1 site in Austria.
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 5 inclusion and 14 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 7 Apr 2015. 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 Austria. 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 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?
β-thromboglobulin (β-TG) (time frame: Changes in shed blood from baseline, at 3 hours, at trough and peak steady state conditions). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Apr 2015.