Dabigatran Etexilate in Patients With Mechanical Heart Valves

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

Official Title
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A Randomised, Phase II Study to Evaluate the sAfety and Pharmacokinetics of oraL dabIGatran Etexilate in Patients After Heart Valve replacemeNt

Conditions
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Heart Valve Diseases

Intervention / Treatment
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* Drug: warfarin 1mg
* Drug: dabigatran etexilate intermediate dose
* Drug: dabigatran etexilate low dose
* Drug: warfarin 5mg
* Drug: dabigatran etexilate high dose
* Drug: warfarin 3mg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients aged 18-75 Patients who have received a bileaflet mechanical heart valve Exclusion criteria: Prior valve surgery Uncontrolled hypertension severe renal impairment active liver disease increased risk of bleeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran etexilate<br>Patient dose dependent on screening CrCl levels and TT | Drug: dabigatran etexilate intermediate dose<br>* active treatment (medium)<br>Drug: dabigatran etexilate low dose<br>* active treatment (low)<br>Drug: dabigatran etexilate high dose<br>* active treatment (high)<br>|
| Active Comparator: warfarin<br>warfarin doses to maintain INR levels | Drug: warfarin 1mg<br>* comparator warfarin<br>Drug: warfarin 5mg<br>* comparator warfarin<br>Drug: warfarin 3mg<br>* comparator warfarin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | Week 12 |