Dabigatran Etexilate in Patients With Mechanical Heart Valves

NCT01452347 | Terminated Phase 2 Results

• 2 other identifiers: 1160.1132010-022685-27
• Study Type: interventional
• Target: 328
• Locations: 10 countries
• Sites: 40

Brief Summary

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

Conditions

Heart Valve Diseases

Outcome Measures

Primary Outcomes (4)

• Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations at Steady State (C Trough,ss) at Week 1

  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.

  Week 1

• Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 2

  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.

  Week 2

• Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 4

  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.

  Week 4

• Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at End of Trial (EoT) at Week 12

  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.

  Week 12

Secondary Outcomes (4)

• Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 1

  Week 1

• Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 2

  Week 2

• Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 4

  Week 4

• Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at End of Trial (EoT) Week 12

  Week 12

Study Arms (2)

Dabigatran etexilate

EXPERIMENTAL

Patient dose dependent on screening CrCl levels and TT

Drug: dabigatran etexilate intermediate dose; Drug: dabigatran etexilate low dose; Drug: dabigatran etexilate high dose

warfarin

ACTIVE COMPARATOR

warfarin doses to maintain INR levels

Drug: warfarin 1mg; Drug: warfarin 5mg; Drug: warfarin 3mg

Interventions

warfarin 1mg DRUG

comparator warfarin

warfarin

dabigatran etexilate intermediate dose DRUG

active treatment (medium)

Dabigatran etexilate

dabigatran etexilate low dose DRUG

active treatment (low)

Dabigatran etexilate

warfarin 5mg DRUG

comparator warfarin

warfarin

dabigatran etexilate high dose DRUG

active treatment (high)

Dabigatran etexilate

warfarin 3mg DRUG

comparator warfarin

warfarin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18-75
• Patients who have received a bileaflet mechanical heart valve

You may not qualify if:

• Prior valve surgery
• Uncontrolled hypertension
• severe renal impairment
• active liver disease
• increased risk of bleeding

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (40)

1160.113.32003 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1160.113.32007 Boehringer Ingelheim Investigational Site

Brussels, Belgium

Location

1160.113.32002 Boehringer Ingelheim Investigational Site

Genk, Belgium

Location

1160.113.32005 Boehringer Ingelheim Investigational Site

Ghent, Belgium

Location

1160.113.32001 Boehringer Ingelheim Investigational Site

Leuven, Belgium

Location

1160.113.11002 Boehringer Ingelheim Investigational Site

Edmonton, Alberta, Canada

Location

1160.113.11006 Boehringer Ingelheim Investigational Site

Winnipeg, Manitoba, Canada

Location

1160.113.11001 Boehringer Ingelheim Investigational Site

Saint John, New Brunswick, Canada

Location

1160.113.11009 Boehringer Ingelheim Investigational Site

Hamilton, Ontario, Canada

Location

1160.113.11011 Boehringer Ingelheim Investigational Site

London, Ontario, Canada

Location

1160.113.11012 Boehringer Ingelheim Investigational Site

Newmarket, Ontario, Canada

Location

1160.113.11007 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

Location

1160.113.42002 Boehringer Ingelheim Investigational Site

Brno, Czechia

Location

1160.113.42005 Boehringer Ingelheim Investigational Site

Hradec Králové, Czechia

Location

1160.113.42003 Boehringer Ingelheim Investigational Site

Olomouc, Czechia

Location

1160.113.42004 Boehringer Ingelheim Investigational Site

Ostrava, Czechia

Location

1160.113.42001 Boehringer Ingelheim Investigational Site

Prague, Czechia

Location

1160.113.45001 Boehringer Ingelheim Investigational Site

Copenhagen, Denmark

Location

1160.113.45002 Boehringer Ingelheim Investigational Site

Odense C, Denmark

Location

1160.113.33004 Boehringer Ingelheim Investigational Site

Bron, France

Location

1160.113.33001 Boehringer Ingelheim Investigational Site

Paris, France

Location

1160.113.33002 Boehringer Ingelheim Investigational Site

Pessac, France

Location

1160.113.33003 Boehringer Ingelheim Investigational Site

Rennes, France

Location

1160.113.49001 Boehringer Ingelheim Investigational Site

Dresden, Germany

Location

1160.113.49002 Boehringer Ingelheim Investigational Site

Essen, Germany

Location

1160.113.49008 Boehringer Ingelheim Investigational Site

Frankfurt am Main, Germany

Location

1160.113.49004 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, Germany

Location

1160.113.49003 Boehringer Ingelheim Investigational Site

Heidelberg, Germany

Location

1160.113.49010 Boehringer Ingelheim Investigational Site

Witten, Germany

Location

1160.113.31001 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1160.113.31002 Boehringer Ingelheim Investigational Site

Amsterdam, Netherlands

Location

1160.113.31004 Boehringer Ingelheim Investigational Site

Breda, Netherlands

Location

1160.113.47002 Boehringer Ingelheim Investigational Site

Bergen, Norway

Location

1160.113.47001 Boehringer Ingelheim Investigational Site

Oslo, Norway

Location

1160.113.48004 Boehringer Ingelheim Investigational Site

Gdansk, Poland

Location

1160.113.48003 Boehringer Ingelheim Investigational Site

Warsaw, Poland

Location

1160.113.48001 Boehringer Ingelheim Investigational Site

Wroclaw, Poland

Location

1160.113.46004 Sahlgrenska Universitetssjukhuset

Gothenburg, Sweden

Location

1160.113.46003 Skånes Universitetssjukhus Lund

Lund, Sweden

Location

1160.113.46001 Akademiska Sjukhuset

Uppsala, Sweden

Location

Related Publications (1)

• Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, Van de Werf F; RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013 Sep 26;369(13):1206-14. doi: 10.1056/NEJMoa1300615. Epub 2013 Aug 31.

  PMID: 23991661 DERIVED

MeSH Terms

Conditions

Heart Valve Diseases

Interventions

Warfarin; Dabigatran

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This study was terminated prematurely due to safety concerns arising during conduct of the trial.

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim Pharmaceuticals

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2011
• First Posted: October 14, 2011
• Study Start: October 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: August 6, 2014
• Results First Posted: August 6, 2014

Record last verified: 2014-07

Locations

DE (6); NO (2); CA (7); NL (3); PL (3); BE (5); FR (4); DK (2); SE (3); CZ (5)