Resolution of Left Atrial-Appendage Thrombus - Effects of Dabigatran in Patients With AF

NCT02256683 | Terminated Phase 2 DMC

• 2 other identifiers: 2013-0082013-005364-26
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 14

Brief Summary

The primary objective of this study is to assess whether Dabigatran leads to a faster complete left atrial appendage (LAA) thrombus resolution as compared to Phenprocoumon. The secondary objectives of this trial are to assess the impact of Dabigatran versus Phenprocoumon on complete LAA thrombus resolution rate until week 6 and change in LAA thrombus volume under treatment as well as to assess and compare safety and tolerability of both drugs. A total of 110 patients with atrial fibrillation and LAA thrombus will be randomized to receive either Dabigatran (150 mg bid) or Phenprocoumon (INR 2-3) for a least three weeks. Thrombus resolution will be determined by transoesophageal echocardiography (TEE) 3 weeks after start of study treatment and subsequently at week 4 and 6 if necessary, i.e. LAA thrombus has not yet resolved. The study is terminated for each patient with the resolution of the LAA thrombus. For those patients whose thrombus still exists after 6 weeks treatment, the study is also terminated. Further treatments will be decided at the discretion of the treating physician.

Conditions

Atrial Fibrillation or Atrial Flutter; Thrombosis of Left Atrial Appendage

Keywords

atrial fibrillation; atrial flutter; Atrial-Appendage Thrombus; Thrombus resolution; Dabigatran; Phenprocoumon; Transesophageal Echocardiography

Outcome Measures

Primary Outcomes (1)

• Time to complete left atrial appendage (LAA) thrombus resolution

  Transoesophageal echocardiography (TEE) will be performed at screening and after three weeks of treatment. In case of persistence of the LAA thrombus after three weeks, study treatment will be continued for a maximum of further 3 weeks and the patients will undergo a TEE at weeks 4 and 6 for LAA thrombus assessment until LAA thrombus resolution can be confirmed. The study is finished for each patient with the resolution of the LAA thrombus. For patients with a thrombus persisting after 6 weeks treatment, the study will also be terminated. At each TEE examination existence of a LAA thrombus is documented (YES/NO).

  3 up to 6 weeks

Secondary Outcomes (8)

• Complete LAA thrombus resolution until week 6 (yes/no)

  3 up to 6 weeks

• Change in LAA thrombus volume under treatment

  3 up to 6 weeks

• Occurrence of any adverse event

  3 up to 6 weeks

• Occurrence of major bleedings

  3 up to 6 weeks

• Occurrence of strokes (all-type, haemorrhagic, ischemic) ascertained by CCT or cMRT

  3 up to 6 weeks

Study Arms (2)

Dabigatran

EXPERIMENTAL

Dabigatran etexilate (Pradaxa®) 150 mg capsule by mouth twice daly for 3 up to 6 weeks depending on treatment response

Drug: Dabigatran etexilate

Phenprocoumon

ACTIVE COMPARATOR

Phenprocoumon (Marcumar®) 3 mg capsule by mouth according to INR (2-3) for 3 up to 6 weeks depending on treatment response

Drug: Phenprocoumon

Interventions

Dabigatran etexilate DRUG

After inclusion of the patients with LAA thrombus, they are treated according to the randomization either with Pradaxa® (150 mg bid) or Marcumar® (INR 2-3) for at least three weeks. Thrombus resolution will be determined by transesophageal echocardiography (TEE) 3 weeks after start of treatment and subsequently at week 4 and 6 if necessary, i.e. LAA thrombus has not yet resolved. The study is terminated for each patient with the resolution of the LAA thrombus or after 6 weeks of study treatment.

Also known as: Pradaxa®

Dabigatran

Phenprocoumon DRUG

After inclusion of the patients with LAA thrombus, they are treated according to the randomization either with Pradaxa® (150 mg bid) or Marcumar® (INR 2-3) for at least three weeks. Thrombus resolution will be determined by transesophageal echocardiography (TEE) 3 weeks after start of treatment and subsequently at week 4 and 6 if necessary, i.e. LAA thrombus has not yet resolved. The study is terminated for each patient with the resolution of the LAA thrombus or after 6 weeks of study treatment.

Also known as: Marcumar®

Phenprocoumon

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with documented non-valvular AF or atrial flutter (12-lead ECG)
• Newly diagnosed or confirmed LAA thrombus in TEE (time of detection ≤ 28 days)
• Patients 18 years old
• CHA2DS2-VASc Score 1
• CrCL 30 mL/min (Cockcroft-Gault)
• Women with childbearing potential have to practice a medically accepted contraception
• Ability of patient to understand the character and the individual consequences of the clinical trial
• Signed and dated informed consent before start of any specific trial procedures

You may not qualify if:

• Patients \> 80 years
• Low body weight (\< 50 kg)
• Previous failure of LAA thrombus resolution with a VKA or factor Xa antagonist
• Occurrence of LAA thrombus under long-term treatment (\> 3 months) with vitamin K antagonists with an exception in the case of continued INR out of the target range
• Contraindications for oral anticoagulation therapy (see current Fachinformation for Pradaxa® (150 mg) and Marcumar® (3 mg))
• History of heart valve disorder (i.e., prosthetic valve or hemodynamically relevant valve disease)
• Valvular heart disease requiring intervention (including mechanical valves)
• Acute myocardial infarction or MI within the last 26 weeks
• Acute coronary syndrome (e.g. instable angina pectoris, STEMI, NSTEMI)
• Chronic Heart Failure (\> NYHA IIIa)
• Previous haemorrhagic stroke
• TIA within the last 90 days
• Clinical relevant bleeding within the last 26 weeks
• Acute and subacute bacterial endocarditis
• Recurrent pulmonary embolism

Sponsors & Collaborators

• Johannes Gutenberg University Mainz: lead
• Boehringer Ingelheim: collaborator
• Atrial Fibrillation Network: collaborator

Study Sites (14)

University Heart Center; Department of Cardiology and Angiology II

Bad Krozingen, D-79189, Germany

Location

Charité Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

Vivantes Clinical Center Am Urban; General Internal Medicine and conservative intensive care

Berlin, D-10967, Germany

Location

Klinikum Coburg GmbH

Coburg, 96450, Germany

Location

University Heart Center; Department of Cardiology

Cologne, D-50937, Germany

Location

University Heart Center; Department of Invasive Electrophysiology

Dresden, D-01307, Germany

Location

University Heart Center; Department of Cardiology, Electrophysiology

Hamburg, D-20246, Germany

Location

Hannover Medical School; Department of Cardiology and Angiology

Hanover, D-30625, Germany

Location

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

Location

Universitätsmedizin Leipzig

Leipzig, 04103, Germany

Location

University Hospital Mainz, II. Medical Clinic, Dept. of Electrophysiology

Mainz, D-55131, Germany

Location

University Medical Center

Münster, D-48149, Germany

Location

St. Vincenz-Hospital GmbH

Paderborn, D-33098, Germany

Location

Rostock University Hospital; Rhythmology and Clinical Electrophysiology

Rostock, D-18057, Germany

Location

MeSH Terms

Conditions

Atrial Fibrillation; Atrial Flutter

Interventions

Dabigatran; Phenprocoumon

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans

Study Officials

• Thomas Rostock, MD

  University Medical Center of the Johannes Gutenberg-University Mainz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Univ.-Prof. Dr. med.

Study Record Dates

• First Submitted: September 12, 2014
• First Posted: October 6, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: July 26, 2019

Record last verified: 2019-07

Locations

DE (14)