Left Atrial Thrombus Reduction - Effect of Dabigatran Versus Phenprocoumon

Atrial Fibrillation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02591225
• Other study ID #: BI 1160.206
• Status: Recruiting
• Phase: Phase 4
• First received: October 28, 2015
• Last updated: November 12, 2015
• Start date: October 2015

Study information

• Verified date: November 2015
• Source: University of Ulm
• Contact: Brigitte Ruess
• Phone: +4973150045250
• Email: brigitte.ruess[@]uniklinik-ulm.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 79 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Left Atrial Thrombosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Germany	Department of Internal Medicine II, University Hospital Ulm	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
University of Ulm	Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	left atrial thrombus resolution	thrombus size evaluated by transeshophageal echocardiography	12 months	No
Secondary	cerebral emolism	cerebral embolic events detected by magnetic resonance imaging	12 months	No