Left Atrial Thrombus Reduction - Effect of Dabigatran Versus Phenprocoumon

Phenprocoumon Versus Dabigatran in Subjects With Atrial Fibrillation and Left Atrial Thrombus - a Prospective, Randomized, Controlled, Open-label One Year Follow-up Pilot Study

This is a single-center, randomized, two treatment groups, open, phase IV clinical study in subjects with atrial fibrillation and left atrial thrombus. At Visit 0 (Screening Visit) subjects with left atrial thrombus established in transesophageal echocardiography (TEE) are eligible to entry in the study. If the subjects fulfill all other in- and exclusion criteria and undersign the informed consent the baseline cranial magnet resonance imaging (MRI) can be performed followed by randomization to one of the two treatment groups (Phenprocoumon or Dabigatran) at Visit 1 (Baseline Visit). The subjects will be treated for 12 months with Phenprocoumon (INR adjusted once daily) or Dabigatran 150 mg twice daily. Routinely clinical follow up visits will be done at week 4, month 3, month 6, month 9 and month 12. Follow up TEE will be performed after 4 weeks and after 12 months also the follow up cranial MRI at this visit. If the subject was randomized in the VKA group routinely INR measurements will performed.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation; Left Atrial Thrombosis
• Intervention / Treatment: Drug: Dabigatranetexilate; Drug: Phenprocoumon

Detailed Description

Bakground and study rationale: Left atrial (LA) thrombi are found in 2.5 - 18% of subjects with atrial fibrillation (AF) depending on the subject population. Subjects with LA thrombi have a particularly increased risk for cerebral and peripheral embolism. Consequently, oral anticoagulation is recommended in those subjects. Transesophageal echocardiography (TEE) is suited and is capable of visualizing and deecting LA thrombi. Cranial magnetic resonance imaging (MRI) has a high accurancy for detecting ailent cerebral mircoembolism. However, under continued effective anticoagulation with the vitamin K antagonist (VKA) Phenprocoumon we have shown that only 56% of LA thrombi resolve during a 12 months TEE observational period. At 1 month only 16% of the thrombi disappeared. However, cureent treatment guidelines recommend 4 weeks of effective anticoagulations prior cardioversion, independent of LA thrombus. In our subject population 84% of LA thrombi would have still been presented at 4 weeks VKA therapy and thus, would have had an increased risk of thromboembolism, if cardioversion, in accordance with current guidelines, would have performed. It is well known that thrombin plays a central role in the formation, growth, maintenance, and consolidation of thrombus. Direct thrombin inhibition has been shown to block these processes and leads to inhibition of thrombus. In vivo, it has been shown to reduce 90% of the preformed, half-hour-old-thrombus. This effect is probably due to better inhibition of the catalytically active clot-bound thrombin. Newer oral anticoagulants, like the direct thrombin inhibitor Dabigatran are therefore very promising for resolution of LA thrombi in comparison to VKA, which has not been investigated previously.

Efficacy variables: Expliration of possible differences for the reduction of left atrial thrombus size evaluated by TEE (primary) and silent cerebral embolism (secondary) detected by cranial MRI at baseline anf after a 12 month treated period with Phenprocoumon or Dabigatran in order to gain mire detailed information and to generate valid hypotheses for further clinical trials.

Overview: This is a single-center, randomized, two treatment groups, open, phase IV clinical study in subjects with atrial fibrillation and left atrial thrombus. At visit 0 (Screening visit) subjects with left atrial thrombus established in TEE are eligable to entry in the study. If the subjects fulfill all other in- and exclusion criteria and undersign the informed consent the baseline cranial MRI can be performed follwoed by randomization to one of the two treatment groups (Phenprocoumon or Dabigatran) at Visit 1 (Baseline visit). The subjects will be treated for 12 months with Phenprocoumon (INR adjusted once daily) or Dabigatran 150 mg twice daily. Routinly clinical follow up visits bill be done at week 4, month 3, month 6, month 9 and month 12. Follow up TEE will be performed after week 4 and month 12 also the follow up cranial MRI at this visit. If the subject was randomized in the VKA group routinely INR measurements will performed.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany, 89081
    • Recruiting
    • Department of Internal Medicine II, University Hospital Ulm
    • Contact: Peter Bernhardt, MD; Phone Number: +49 731 500-45060; Email: peter.bernhardt@uniklinik-ulm.de
    • Contact: Brigitte Ruess; Phone Number: +49 731 500-45246; Email: brigitte.ruess@uniklinik-ulm.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• signed and dated written informed consent
• atrail fibrillation
• left atrial thrombus
• negative pregnancy test in woman with childbearin potentail
• subjects who have the ability to understand and comply the instructions for participation

Exclusion Criteria:

• low body weight < 50 kg
• instable cardiac or respiratory condition
• contraindication for Phenprocoumon or Dabigatran
• severely reduced renal function (CrCl < 30 ml/min)
• inadequate hepatic function (AST and ALT higher than 2 x ULN)
• Contraindication for MRI
• Durg/alcohol abusus
• Pregnant or nursing woman
• subject is an employee of any involved study investigator
• Parallel participation in another clinical trial
• Treatment with another investigational product

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dabigatranetexilate; Dabigatran capsula 150 mg; oral; bid; treatment period 12 months	Drug: Dabigatranetexilate; After inclusion of the subjects with LA thrombus, they are treated according to the randomization either with Dabigatran (150 mg bid) or Phenprocoumon (INR adjusted once) for the treatment period of 12 months.; Other Names: Pradaxa
Active Comparator: Phenprocoumon; Phenprocoumon INR adjusted; oral; once daily; treatment period 12 months	Drug: Phenprocoumon; After inclusion of the subjects with LA thrombus, they are treated according to the randomization either with Dabigatran (150 mg bid) or Phenprocoumon (INR adjusted once) for the treatment period of 12 months.; Other Names: Marcumar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
left atrial thrombus resolution	thrombus size evaluated by transeshophageal echocardiography	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cerebral emolism	cerebral embolic events detected by magnetic resonance imaging	12 months

Collaborators and Investigators

• Sponsor: University of Ulm
• Collaborators: Boehringer Ingelheim
• Investigators: Principal Investigator: Peter Bernhardt, MD, University Hospital Ulm, Department of Internal Medicine II

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: October 28, 2015
• First Submitted That Met QC Criteria: October 28, 2015
• First Posted (Estimate): October 29, 2015

Study Record Updates

• Last Update Posted (Estimate): November 13, 2015
• Last Update Submitted That Met QC Criteria: November 12, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: left atrial thrombus size; transesophageale echocardiography; silent cerebral embolism
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Arrhythmias, Cardiac; Atrial Fibrillation; Thrombosis; Anticoagulants; Phenprocoumon
• Other Study ID Numbers: BI 1160.206