Heart Valve DiseasesPhase 2RE-ALIGNNCT01452347
Dabigatran Etexilate in Patients With Mechanical Heart Valves
A Phase 2 study testing warfarin 1mg, dabigatran etexilate intermediate dose and dabigatran etexilate low dose in people with Heart Valve Diseases, run by Boehringer Ingelheim at 40 sites in 10 countries.
Trial summary
To validate the dosing algorithm for dabigatran etexilate in patients receiving a mechanical heart valve. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Heart Valve Diseases
- What is being tested?
- warfarin 1mg, dabigatran etexilate intermediate dose and dabigatran etexilate low dose
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 328 participants
- Where
- 40 sitesin 10 countries
- Study dates
- Oct 2011to Jun 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 18-75
- Patients who have received a bileaflet mechanical heart valve
Who cannot join
- Prior valve surgery
- Uncontrolled hypertension
- severe renal impairment
- active liver disease
- increased risk of bleeding
Trial locations and contacts
40 sites in 10 countries.
40 sites in 10 countries
Canada7 sites
1160.113.11002 Boehringer Ingelheim Investigational Site
Edmonton, Alberta
1160.113.11009 Boehringer Ingelheim Investigational Site
Hamilton, Ontario
1160.113.11011 Boehringer Ingelheim Investigational Site
London, Ontario
1160.113.11012 Boehringer Ingelheim Investigational Site
Newmarket, Ontario
1160.113.11001 Boehringer Ingelheim Investigational Site
Saint John, New Brunswick
1160.113.11007 Boehringer Ingelheim Investigational Site
Toronto, Ontario
1160.113.11006 Boehringer Ingelheim Investigational Site
Winnipeg, Manitoba
Germany6 sites
1160.113.49001 Boehringer Ingelheim Investigational Site
Dresden
1160.113.49002 Boehringer Ingelheim Investigational Site
Essen
1160.113.49008 Boehringer Ingelheim Investigational Site
Frankfurt am Main
1160.113.49004 Boehringer Ingelheim Investigational Site
Freiburg im Breisgau
1160.113.49003 Boehringer Ingelheim Investigational Site
Heidelberg
1160.113.49010 Boehringer Ingelheim Investigational Site
Witten
Belgium5 sites
1160.113.32003 Boehringer Ingelheim Investigational Site
Brussels
1160.113.32007 Boehringer Ingelheim Investigational Site
Brussels
1160.113.32002 Boehringer Ingelheim Investigational Site
Genk
1160.113.32005 Boehringer Ingelheim Investigational Site
Ghent
1160.113.32001 Boehringer Ingelheim Investigational Site
Leuven
Czechia5 sites
1160.113.42002 Boehringer Ingelheim Investigational Site
Brno
1160.113.42005 Boehringer Ingelheim Investigational Site
Hradec Králové
1160.113.42003 Boehringer Ingelheim Investigational Site
Olomouc
1160.113.42004 Boehringer Ingelheim Investigational Site
Ostrava
1160.113.42001 Boehringer Ingelheim Investigational Site
Prague
France4 sites
1160.113.33004 Boehringer Ingelheim Investigational Site
Bron
1160.113.33001 Boehringer Ingelheim Investigational Site
Paris
1160.113.33002 Boehringer Ingelheim Investigational Site
Pessac
1160.113.33003 Boehringer Ingelheim Investigational Site
Rennes
Netherlands3 sites
1160.113.31001 Boehringer Ingelheim Investigational Site
Amsterdam
1160.113.31002 Boehringer Ingelheim Investigational Site
Amsterdam
1160.113.31004 Boehringer Ingelheim Investigational Site
Breda
Poland3 sites
1160.113.48004 Boehringer Ingelheim Investigational Site
Gdansk
1160.113.48003 Boehringer Ingelheim Investigational Site
Warsaw
1160.113.48001 Boehringer Ingelheim Investigational Site
Wroclaw
Sweden3 sites
1160.113.46004 Sahlgrenska Universitetssjukhuset
Gothenburg
1160.113.46003 Skånes Universitetssjukhus Lund
Lund
1160.113.46001 Akademiska Sjukhuset
Uppsala
Denmark2 sites
1160.113.45001 Boehringer Ingelheim Investigational Site
Copenhagen
1160.113.45002 Boehringer Ingelheim Investigational Site
Odense C
Norway2 sites
1160.113.47002 Boehringer Ingelheim Investigational Site
Bergen
1160.113.47001 Boehringer Ingelheim Investigational Site
Oslo
About this study
Official title: A Randomised, Phase II Study to Evaluate the sAfety and Pharmacokinetics of oraL dabIGatran Etexilate in Patients After Heart Valve replacemeNt
To validate the dosing algorithm for dabigatran etexilate in patients receiving a mechanical heart valve.
- Conditions
- Heart Valve Diseases
- Being tested
- warfarin 1mg, dabigatran etexilate intermediate dose, dabigatran etexilate low dose, warfarin 5mg, dabigatran etexilate high dose
- Medical subject headings
- Heart Valve Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
warfarin 1mgDrug
comparator warfarin
dabigatran etexilate intermediate doseDrug
active treatment (medium)
dabigatran etexilate low doseDrug
active treatment (low)
warfarin 5mgDrug
comparator warfarin
dabigatran etexilate high doseDrug
active treatment (high)
warfarin 3mgDrug
comparator warfarin
| Study group | Role | What they receive |
|---|---|---|
| Dabigatran etexilate | Experimental | Patient dose dependent on screening CrCl levels and TT Receives: Drug: dabigatran etexilate intermediate dose; Drug: dabigatran etexilate low dose; Drug: dabigatran etexilate high dose |
| warfarin | Active comparator | warfarin doses to maintain INR levels Receives: Drug: warfarin 1mg; Drug: warfarin 5mg; Drug: warfarin 3mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Week 12
Secondary outcomes (4)
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 1
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.
Measured: Week 1
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 2
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.
Measured: Week 2
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 4
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.
Measured: Week 4
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at End of Trial (EoT) Week 12
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.
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart Valve DiseasesStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 328 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01452347
- Sponsor's protocol ID
- 1160.113
- Other IDs
- 2010-022685-27
- Acronym
- RE-ALIGN
- Status last verified
- Jul 2014
- First submitted
- 11 Oct 2011
- Last updated
- 6 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 23991661
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Phase II Study to Evaluate the sAfety and Pharmacokinetics of oraL dabIGatran Etexilate in Patients After Heart Valve replacemeNt
- ClinicalTrials.gov ID
- NCT01452347
- Acronym / sponsor ID
- RE-ALIGN / 1160.113
- Conditions
- Heart Valve Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 328 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- Oct 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 14 Oct 2011 (estimated)
- Results
- Posted 6 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To validate the dosing algorithm for dabigatran etexilate in patients receiving a mechanical heart valve.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dabigatran etexilate | Experimental | Drug: dabigatran etexilate intermediate dose, Drug: dabigatran etexilate low dose, Drug: dabigatran etexilate high dosePatient dose dependent on screening CrCl levels and TT |
| warfarin | Active comparator | Drug: warfarin 1mg, Drug: warfarin 5mg, Drug: warfarin 3mgwarfarin doses to maintain INR levels |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients aged 18-75
- Patients who have received a bileaflet mechanical heart valve
Key exclusion criteria (5 listed)
- Prior valve surgery
- Uncontrolled hypertension
- severe renal impairment
- active liver disease
- increased risk of bleeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| warfarin 1mgcomparator warfarin | Drug | warfarin |
| dabigatran etexilate intermediate doseactive treatment (medium) | Drug | Dabigatran etexilate |
| dabigatran etexilate low doseactive treatment (low) | Drug | Dabigatran etexilate |
| warfarin 5mgcomparator warfarin | Drug | warfarin |
| dabigatran etexilate high doseactive treatment (high) | Drug | Dabigatran etexilate |
| warfarin 3mgcomparator warfarin | Drug | warfarin |
Primary outcome
Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations at Steady State (C Trough,ss) at Week 1
Time frame: 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.
Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 2
Time frame: 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.
Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at Week 4
Time frame: 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.
Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations (C Trough,ss) at End of Trial (EoT) at Week 12
Time frame: 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.
4 secondary outcomes
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 1
Time frame: Week 1
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 2
Time frame: Week 2
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at Week 4
Time frame: Week 4
Percentage of Patients With Observed Trough Dabigatran Plasma Concentrations < 50 ng/mL at End of Trial (EoT) Week 12
Time frame: Week 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23991661Eikelboom 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.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
40 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing warfarin 1mg, dabigatran etexilate intermediate dose and dabigatran etexilate low dose in people with Heart Valve Diseases, run by Boehringer Ingelheim at 40 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in Canada, Germany, Belgium, Czechia, France and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of Observed and Predicted Trough Dabigatran Plasma Concentrations at Steady State (C Trough,ss) at Week 1 (time frame: Week 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01452347, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2014.