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Trial record 78 of 157 for:    warfarin AND Vitamin K

Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus

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ClinicalTrials.gov Identifier: NCT03232398
Recruitment Status : Recruiting
First Posted : July 28, 2017
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
RONNY ALCALAI, Hadassah Medical Organization

Tracking Information
First Submitted Date  ICMJE July 16, 2017
First Posted Date  ICMJE July 28, 2017
Last Update Posted Date August 7, 2019
Actual Study Start Date  ICMJE January 1, 2018
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03232398 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
  • Stroke or systemic embolism [ Time Frame: 3 months ]
    Clinically significant stroke or systemic embolism requiring hospitalization
  • Major bleeding [ Time Frame: 3 months ]
    Major bleeding, according to the criteria of the International Society on Thrombosis and Haemostasis (ISTH)
  • All cause mortality [ Time Frame: 3 months ]
    Death from any cause.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
Official Title  ICMJE Apixaban Versus Warfarin in Patients With Left Ventricular (LV) Thrombus
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description:
The primary efficacy endpoint will be the presence of LV thrombus as assessed be echocardiography after 3 months of treatment. Echocardiography images will be reviewed for the presence of LV thrombus by two experts who will be blinded to the study drug.
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myocardial Infarction
  • Left Ventricular Thrombosis
  • Anticoagulants and Bleeding Disorders
Intervention  ICMJE
  • Drug: Apixaban Oral Tablet [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.
    Other Name: Eliquis
  • Drug: Warfarin
    Dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months
    Other Name: Coumadin
Study Arms  ICMJE
  • Active Comparator: Apixaban
    Apixaban Oral Tablet [Eliquis]
    Interventions:
    • Drug: Apixaban Oral Tablet [Eliquis]
    • Drug: Warfarin
  • Active Comparator: Warfarin
    Warfarin - Vitamin K antagonist
    Interventions:
    • Drug: Apixaban Oral Tablet [Eliquis]
    • Drug: Warfarin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 25, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 31, 2020
Estimated Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with evidence of LV thrombus as assessed by trans-thoracic echocardiography
  • Acute MI in last 3 months prior to enrollment

Exclusion Criteria:

  • Patients with contraindications for chronic anti coagulation
  • Patients with severe renal failure (CrCl< 15 ml/min)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Ronny Alcalai, MD +972508946269 ronny@hadassah.org.il
Contact: David Leibowitz, MD +97225844530 oleibo@hadassah.org.il
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03232398
Other Study ID Numbers  ICMJE Hadassah 0607-16
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party RONNY ALCALAI, Hadassah Medical Organization
Study Sponsor  ICMJE Hadassah Medical Organization
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Ronny Alcalai Hadassah Medical Organization
PRS Account Hadassah Medical Organization
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP