Dabigatran Etexilate in Patients With Mechanical Heart Valves (RE-ALIGN)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01452347
First received: October 11, 2011
Last updated: July 11, 2014
Last verified: July 2014
  Purpose

To validate the dosing algorithm for dabigatran etexilate in patients receiving a mechanical heart valve.


Condition Intervention Phase
Heart Valve Diseases
Drug: warfarin 1mg
Drug: dabigatran etexilate intermediate dose
Drug: dabigatran etexilate low dose
Drug: warfarin 5mg
Drug: dabigatran etexilate high dose
Drug: warfarin 3mg
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Randomised, Phase II Study to Evaluate the sAfety and Pharmacokinetics of oraL dabIGatran Etexilate in Patients After Heart Valve replacemeNt

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations at Steady State (C Trough,ss) at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]

    Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE) .

    Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population.


  • Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]

    Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE).

    Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population.


  • Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]

    Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE).

    Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population.


  • Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at End of Trial (EoT) at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]

    Comparisons between dabigatran trough plasma levels as predicted by simulations to those observed in the study are performed to validate the dosing algorithm for Dabigatran Etexilate (DE).

    (As the trial was stopped prematurely, EOT may not be 12 weeks after randomisation for most of the patients)

    Despite the primary endpoint only being assessed in patients who received dabigatran etexilate, Warfarin was included as a comparator treatment in this study in order to facilitate informal comparisons of outcome events, and to look for efficacy signals in this previously unexplored population.



Secondary Outcome Measures:
  • Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 1 [ Time Frame: Week 1 ] [ Designated as safety issue: No ]
    Percentage of patients with observed Ctrough,ss value < 50 ng/mL are presented. This outcome measure was only analysed for all patients together and not by dose group.

  • Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
    Percentage of patients with observed Ctrough,ss value < 50 ng/mL are presented. This outcome measure was only analysed for all patients together and not by dose group.

  • Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    Percentage of patients with observed Ctrough,ss value < 50 ng/mL are presented. This outcome measure was only analysed for all patients together and not by dose group.

  • Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at End of Trial (EoT) Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Percentage of patients with observed Ctrough,ss value < 50 ng/mL (As the trial was stopped prematurely, EOT may not be 12 weeks after randomisation for most of the patients) This outcome measure was only analysed for all patients together and not by dose group.


Enrollment: 328
Study Start Date: October 2011
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran etexilate
Patient dose dependent on screening CrCl levels and TT
Drug: dabigatran etexilate intermediate dose
active treatment (medium)
Drug: dabigatran etexilate low dose
active treatment (low)
Drug: dabigatran etexilate high dose
active treatment (high)
Active Comparator: warfarin
warfarin doses to maintain INR levels
Drug: warfarin 1mg
comparator warfarin
Drug: warfarin 5mg
comparator warfarin
Drug: warfarin 3mg
comparator warfarin

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Patients aged 18-75
  2. Patients who have received a bileaflet mechanical heart valve

Exclusion criteria:

  1. Prior valve surgery
  2. Uncontrolled hypertension
  3. severe renal impairment
  4. active liver disease
  5. increased risk of bleeding
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01452347

  Hide Study Locations
Locations
Belgium
1160.113.32007 Boehringer Ingelheim Investigational Site
Brussel, Belgium
1160.113.32003 Boehringer Ingelheim Investigational Site
Bruxelles, Belgium
1160.113.32002 Boehringer Ingelheim Investigational Site
Genk, Belgium
1160.113.32005 Boehringer Ingelheim Investigational Site
Gent, Belgium
1160.113.32001 Boehringer Ingelheim Investigational Site
Leuven, Belgium
Canada, Alberta
1160.113.11002 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, Manitoba
1160.113.11006 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba, Canada
Canada, New Brunswick
1160.113.11001 Boehringer Ingelheim Investigational Site
Saint John, New Brunswick, Canada
Canada, Ontario
1160.113.11009 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
1160.113.11011 Boehringer Ingelheim Investigational Site
London, Ontario, Canada
1160.113.11012 Boehringer Ingelheim Investigational Site
Newmarket, Ontario, Canada
1160.113.11007 Boehringer Ingelheim Investigational Site
Toronto, Ontario, Canada
Czech Republic
1160.113.42002 Boehringer Ingelheim Investigational Site
Brno, Czech Republic
1160.113.42005 Boehringer Ingelheim Investigational Site
Hradec Kralove, Czech Republic
1160.113.42003 Boehringer Ingelheim Investigational Site
Olomouc, Czech Republic
1160.113.42004 Boehringer Ingelheim Investigational Site
Ostrava, Czech Republic
1160.113.42001 Boehringer Ingelheim Investigational Site
Prague 5, Czech Republic
Denmark
1160.113.45001 Boehringer Ingelheim Investigational Site
Copenhagen, Denmark
1160.113.45002 Boehringer Ingelheim Investigational Site
Odense C, Denmark
France
1160.113.33004 Boehringer Ingelheim Investigational Site
Bron, France
1160.113.33001 Boehringer Ingelheim Investigational Site
Paris cedex 18, France
1160.113.33002 Boehringer Ingelheim Investigational Site
Pessac, France
1160.113.33003 Boehringer Ingelheim Investigational Site
Rennes Cedex 2, France
Germany
1160.113.49001 Boehringer Ingelheim Investigational Site
Dresden, Germany
1160.113.49002 Boehringer Ingelheim Investigational Site
Essen, Germany
1160.113.49008 Boehringer Ingelheim Investigational Site
Frankfurt am Main, Germany
1160.113.49004 Boehringer Ingelheim Investigational Site
Freiburg, Germany
1160.113.49003 Boehringer Ingelheim Investigational Site
Heidelberg, Germany
1160.113.49010 Boehringer Ingelheim Investigational Site
Witten, Germany
Netherlands
1160.113.31001 Boehringer Ingelheim Investigational Site
Amsterdam, Netherlands
1160.113.31002 Boehringer Ingelheim Investigational Site
Amsterdam, Netherlands
1160.113.31004 Boehringer Ingelheim Investigational Site
Breda, Netherlands
Norway
1160.113.47002 Boehringer Ingelheim Investigational Site
Bergen, Norway
1160.113.47001 Boehringer Ingelheim Investigational Site
Oslo, Norway
Poland
1160.113.48004 Boehringer Ingelheim Investigational Site
Gdansk, Poland
1160.113.48003 Boehringer Ingelheim Investigational Site
Warszawa, Poland
1160.113.48001 Boehringer Ingelheim Investigational Site
Wroclaw, Poland
Sweden
1160.113.46004 Sahlgrenska Universitetssjukhuset
Göteborg, Sweden
1160.113.46003 Skånes Universitetssjukhus Lund
Lund, Sweden
1160.113.46001 Akademiska Sjukhuset
Uppsala, Sweden
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01452347     History of Changes
Other Study ID Numbers: 1160.113, 2010-022685-27
Study First Received: October 11, 2011
Results First Received: May 23, 2014
Last Updated: July 11, 2014
Health Authority: Belgium: Federal Agency for Medicinal and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Netherlands: Central Committee Research Involving Human Subjects
Norway: Norwegian Medicines Agency
Poland: Registration Medicinal Product Medical Device Biocidal Product
Sweden: Medical Products Agency
United States: Food and Drug Administration

Additional relevant MeSH terms:
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Dabigatran
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014