Acute Myocardial InfarctionPhase 3NCT03232398
Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
A Phase 3 study testing Apixaban Oral Tablet [Eliquis] and Warfarin in people with Acute Myocardial Infarction and Left Ventricular Thrombosis, run by Hadassah Medical Organization at 1 site in Israel.
Trial summary
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Acute Myocardial Infarction, Left Ventricular Thrombosis, Anticoagulants and Bleeding Disorders
- What is being tested?
- Apixaban Oral Tablet [Eliquis] and Warfarin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jan 2018to 31 May 2021
- Phase
- Phase 3
- 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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography
- Acute MI in last 3 months prior to enrollment
Who cannot join
- Patients with contraindications for chronic anti coagulation
- Patients with severe renal failure (CrCl< 15 ml/min)
Trial locations and contacts
1 site in 1 country.
About this study
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI.
In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent [3]. Although there are no randomized trials evaluating the efficacy of anticoagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anticoagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction. Currently the practice guidelines recommend anticoagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation. To date there are no data on the use of novel oral anticoagulants (NOACS) for stroke prevention in the setting of LV thrombus after acute MI.
Read more
The proposed aim of this randomized open label non inferiority clinical trial is to assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.
Population: Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography (TTE) 3 to 7 days post admission for acute ST-elevation MI
Intervention: The patients will be randomly assigned to treatment with apixaban or s.c enoxaparin 1mg/Kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months.
The study Outcomes are the presence of LV thrombus as assessed be echo, major bleeding, and stroke or systemic embolism and death from any cause.
Read the detailed description
Background and Study Rationale:
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. The risk for stroke after myocardial infarction (MI) is estimated to be 44-fold higher within the first 30 days, and remains 2 to 3 times higher than expected during the subsequent 3 years. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI [2].
In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent. Although there are no randomized trials evaluating the efficacy of anti coagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anti coagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction.
Treatment of myocardial infarction has evolved dramatically in the past 20 years, and the vast majorities of patients undergo early coronary intervention and receive dual anti platelet therapy (DAPT). As a result, anterior MI alone does not warrant anti coagulation without evidence of LV thrombus since the combination of oral anti coagulation with DAPT carries an increased risk of bleeding. Practice guidelines recommend anti coagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation [5].
Recently oral thrombin inhibitors and factor Xa inhibitors (terms as novel oral anticoagulants - NOACS) have been introduced for stroke prevention in patients with non-valvular atrial fibrillation [6-8]. These agents were shown to be at least as effective as Vitamin K antagonists (VKA) such as warfarin in prevention of systemic embolism, while having an improved safety profile with less risk of bleeding.
To date there are no data on the use of NOACS for stroke prevention in the setting of LV thrombus after acute MI. Consequently, the effectiveness and safety of anti coagulation therapy with these novel agents in patients with LV thrombus warrants further investigation. The devastating impact of a stroke after an MI on morbidity and mortality, and the increasing number of patients at risk because of improved post-MI survival, making the goal of prevention of post MI stroke a major public health concern. The proposed study aims to address this important clinical topic.
Objective:
To assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.
Design Randomized open label non inferiority clinical trial.
- Conditions
- Acute Myocardial Infarction, Left Ventricular Thrombosis, Anticoagulants and Bleeding Disorders
- Being tested
- Apixaban Oral Tablet [Eliquis], Warfarin
- Medical subject headings
- Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban Oral Tablet [Eliquis]Drug
Also called Eliquis
Apixaban 5 mg BID for 3 months. Apixaban 2.5-mg BID doses will be used in a subset of patients with two or more of the following criteria: an age of at least 80 years, a body weight of no more than 60 kg, or a serum creatinine level of 1.5 mg per deciliter (133 μmol per liter) or more. Patients with advanced renal failure (CrCl between 15 ml/min and 29 mi/min) will also receive 2.5 mg BID.
WarfarinDrug
Also called Coumadin
Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Active comparator | Apixaban Oral Tablet [Eliquis] Receives: Drug: Apixaban Oral Tablet [Eliquis]; Drug: Warfarin |
| Warfarin | Active comparator | Warfarin - Vitamin K antagonist Receives: Drug: Apixaban Oral Tablet [Eliquis]; Drug: Warfarin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence and dimensions of Left ventricular thrombus (LV) as assessed by 2D echocardiography
The primary efficacy endpoint will be the presence of LV thrombus as assessed be echocardiography after 3 months of treatment with oral anti coagulation. Dimensions of the LV thrombus (if still present) will be compared to the thrombus dimensions at baseline.
Measured: 3 months
Secondary outcomes (3)
Stroke or systemic embolism
Clinically significant stroke or systemic embolism requiring hospitalization
Measured: 3 months
Major bleeding
Major bleeding, according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH)
Measured: 3 months
All cause mortality
Death from any cause.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2017
- Study start1 Jan 2018
- Primary completion31 Mar 2021
- Study completion31 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acute Myocardial InfarctionStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, RONNY ALCALAI, Hadassah Medical Organization
- Investigators
- Ronny Alcalai, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03232398
- Sponsor's protocol ID
- Hadassah 0607-16
- Status last verified
- Aug 2021
- First submitted
- 16 Jul 2017
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Yawn BP, Roger VL. A community-based study of stroke incidence after myocardial infarction. Ann Intern Med. 2005 Dec 6;143(11):785-92. doi: 10.7326/0003-4819-143-11-200512060-00006.
PubMed 16330789Fuster V, Halperin JL. Left ventricular thrombi and cerebral embolism. N Engl J Med. 1989 Feb 9;320(6):392-4. doi: 10.1056/NEJM198902093200610. No abstract available.
PubMed 2913497Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993 Oct;22(4):1004-9. doi: 10.1016/0735-1097(93)90409-t.
PubMed 8409034Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.
PubMed 21870978Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
PubMed 15842354
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
- ClinicalTrials.gov ID
- NCT03232398
- Acronym / sponsor ID
- Hadassah 0607-16
- Conditions
- Acute Myocardial Infarction, Left Ventricular Thrombosis, Anticoagulants and Bleeding Disorders
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 May 2021 (actual)
- First posted
- 28 Jul 2017 (actual)
- 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.
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI.
In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent [3]. Although there are no randomized trials evaluating the efficacy of anticoagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anticoagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction. Currently the practice guidelines recommend anticoagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation. To date there are no data on the use of novel oral anticoagulants (NOACS) for stroke prevention in the setting of LV thrombus after acute MI.
The proposed aim of this randomized open label non inferiority clinical trial is to assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.
Population: Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography (TTE) 3 to 7 days post admission for acute ST-elevation MI
Intervention: The patients will be randomly assigned to treatment with apixaban or s.c enoxaparin 1mg/Kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months.
The study Outcomes are the presence of LV thrombus as assessed be echo, major bleeding, and stroke or systemic embolism and death from any cause.
Detailed description
Background and Study Rationale:
Patients with acute ST-segment elevation myocardial infarction (STEMI) have an elevated risk of stroke, most of which are cardio-embolic in origin as a result of left ventricular (LV) thrombus formation. The risk for stroke after myocardial infarction (MI) is estimated to be 44-fold higher within the first 30 days, and remains 2 to 3 times higher than expected during the subsequent 3 years. Anterior-wall location of a MI, in particular, can lead to the complications of LV aneurysm and/or thrombus, which some estimate occurs in approximately up to one-third of individuals within the first 2 weeks following an anterior MI [2].
In the absence of anti coagulation, the risk of embolization in patients with a documented LV thrombus has been reported to be between 10 and 15 percent. Although there are no randomized trials evaluating the efficacy of anti coagulation in patients with an LV thrombus after MI, observational studies provide substantial supporting evidence for the recommendation to anti coagulate patients with documented LV thrombus in order to reduce the risk of embolization. The observation that most events occur within the first three months from the MI forms the basis for the recommendation that anticoagulant therapy should be started early and continued for at least three to six months after myocardial infarction.
Treatment of myocardial infarction has evolved dramatically in the past 20 years, and the vast majorities of patients undergo early coronary intervention and receive dual anti platelet therapy (DAPT). As a result, anterior MI alone does not warrant anti coagulation without evidence of LV thrombus since the combination of oral anti coagulation with DAPT carries an increased risk of bleeding. Practice guidelines recommend anti coagulation after MI only in certain settings such as the presence of LV thrombus or atrial fibrillation [5].
Recently oral thrombin inhibitors and factor Xa inhibitors (terms as novel oral anticoagulants - NOACS) have been introduced for stroke prevention in patients with non-valvular atrial fibrillation [6-8]. These agents were shown to be at least as effective as Vitamin K antagonists (VKA) such as warfarin in prevention of systemic embolism, while having an improved safety profile with less risk of bleeding.
To date there are no data on the use of NOACS for stroke prevention in the setting of LV thrombus after acute MI. Consequently, the effectiveness and safety of anti coagulation therapy with these novel agents in patients with LV thrombus warrants further investigation. The devastating impact of a stroke after an MI on morbidity and mortality, and the increasing number of patients at risk because of improved post-MI survival, making the goal of prevention of post MI stroke a major public health concern. The proposed study aims to address this important clinical topic.
Objective:
To assess whether apixaban is as effective as VKA for the treatment of LV thrombus after acute ST segment elevation MI.
Design Randomized open label non inferiority clinical trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Active comparator | Drug: Apixaban Oral Tablet [Eliquis], Drug: WarfarinApixaban Oral Tablet [Eliquis] |
| Warfarin | Active comparator | Drug: Apixaban Oral Tablet [Eliquis], Drug: WarfarinWarfarin - Vitamin K antagonist |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography
- Acute MI in last 3 months prior to enrollment
Key exclusion criteria (2 listed)
- Patients with contraindications for chronic anti coagulation
- Patients with severe renal failure (CrCl< 15 ml/min)
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 |
|---|---|---|
| Apixaban Oral Tablet [Eliquis]Also: EliquisApixaban 5 mg BID for 3 months. Apixaban 2.5-mg BID doses will be used in a subset of patients with two or more of the following criteria: an age of at least 80 years, a body weight of no more than 60 kg, or a serum creatinine level of 1.5 mg per deciliter (133 μmol per liter) or more. Patients with advanced renal failure (CrCl between 15 ml/min and 29 mi/min) will also receive 2.5 mg BID. | Drug | Apixaban, Warfarin |
| WarfarinAlso: CoumadinDose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months | Drug | Apixaban, Warfarin |
Primary outcome
Presence and dimensions of Left ventricular thrombus (LV) as assessed by 2D echocardiography
Time frame: 3 months
The primary efficacy endpoint will be the presence of LV thrombus as assessed be echocardiography after 3 months of treatment with oral anti coagulation. Dimensions of the LV thrombus (if still present) will be compared to the thrombus dimensions at baseline.
3 secondary outcomes
Stroke or systemic embolism
Time frame: 3 months
Major bleeding
Time frame: 3 months
All cause mortality
Time frame: 3 months
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 25 Aug 2021.
- Background: PubMed 16330789Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Yawn BP, Roger VL. A community-based study of stroke incidence after myocardial infarction. Ann Intern Med. 2005 Dec 6;143(11):785-92. doi: 10.7326/0003-4819-143-11-200512060-00006.
- Background: PubMed 2913497Fuster V, Halperin JL. Left ventricular thrombi and cerebral embolism. N Engl J Med. 1989 Feb 9;320(6):392-4. doi: 10.1056/NEJM198902093200610. No abstract available.
- Background: PubMed 8409034Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol. 1993 Oct;22(4):1004-9. doi: 10.1016/0735-1097(93)90409-t.
- Background: PubMed 21870978Granger CB, Alexander JH, McMurray JJ, Lopes RD, Hylek EM, Hanna M, Al-Khalidi HR, Ansell J, Atar D, Avezum A, Bahit MC, Diaz R, Easton JD, Ezekowitz JA, Flaker G, Garcia D, Geraldes M, Gersh BJ, Golitsyn S, Goto S, Hermosillo AG, Hohnloser SH, Horowitz J, Mohan P, Jansky P, Lewis BS, Lopez-Sendon JL, Pais P, Parkhomenko A, Verheugt FW, Zhu J, Wallentin L; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011 Sep 15;365(11):981-92. doi: 10.1056/NEJMoa1107039. Epub 2011 Aug 27.
- Background: PubMed 15842354Schulman S, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005 Apr;3(4):692-4. doi: 10.1111/j.1538-7836.2005.01204.x.
- Individual participant dataSharing planned: No
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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.
Ronny Alcalai principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban Oral Tablet [Eliquis] and Warfarin in people with Acute Myocardial Infarction and Left Ventricular Thrombosis, run by Hadassah Medical Organization at 1 site in Israel.
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 2 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 25 Aug 2021. 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 Israel. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Presence and dimensions of Left ventricular thrombus (LV) as assessed by 2D echocardiography (time frame: 3 months). 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 NCT03232398, which also lists 5 linked publications.
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 25 Aug 2021.