RE-DEEM Dose Finding Study for Dabigatran Etexilate in Patients With Acute Coronary Syndrome

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the safety and indicators of efficacy of up to 4 doses of orally administered dabigatran etexilate, administered twice daily, compared to placebo when given in addition to dual antiplatelet treatment in patients with an index event (MI) at high risk for new ischaemic cardiovascular events.

Official Title
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RandomizEd Dabigatran Etexilate Dose Finding Study in Patients With Acute Coronary Syndromes Post Index Event With Additional Risk Factors for Cardiovascular Complications Also Receiving Aspirin and Clopidogrel: Multi-centre, Prospective, Placebo Controlled, Cohort Dose Escalation Study (RE-DEEM)

Conditions
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Coronary Disease

Intervention / Treatment
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* Drug: placebo
* Drug: dabigatran etexilate
* Drug: dabigatran etexilate
* Drug: dabigatran etexilate
* Drug: dabigatran etexilate


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Patients with acute coronary syndromes with at least one additional risk factor for cardiovascular complications. Exclusion criteria Long term treatment with any other oral anticoagulant Severe/disabling stroke within last 6 months Conditions associated with increased bleeding risk Anaemia or thrombocytopenia Severe renal impairment Liver disease Positive pregnancy test

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran etexilate 50mg<br>twice daily dosing, | Drug: dabigatran etexilate<br>* capsules, twice daily, 26 weeks treatment<br>|
| Experimental: Dabigatran etexilate 75mg<br>twice daily dosing, patients with moderate renal impairment allocated 50mg bid | Drug: dabigatran etexilate<br>* capsules, twice daily, 26 weeks treatment<br>|
| Experimental: Dabigatran etexilate 110mg<br>twice daily dosing, patients with moderate renal impairment allocated 75mg bid | Drug: dabigatran etexilate<br>* capsules, twice daily, 26 weeks treatment<br>|
| Experimental: dabigatran etexilate 150mg<br>twice daily dosing, patients with moderate renal impairment allocated 110mg bid | Drug: dabigatran etexilate<br>* capsules, twice daily, 26 weeks treatment<br>|
| Placebo Comparator: placebo<br>matched placebo | Drug: placebo<br>* matched placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Displaying the Composite of Major and Clinically Relevant Minor Bleeding Events During Total Observation Time | International Society Thrombosis and Haemostasis (ISTH) definition of a major bleed, and clinically relevant minor bleed. A bleeding event was considered as major if it was fatal, was a symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome), or caused a fall in haemoglobin level of ≥2 g/dL (≥1.24 mmol/L), or led to transfusion of ≥2 units of whole blood or red cells. All non major bleeding events were classified as minor bleeds; minor bleeds were subdivided in clinically relevant minor bleeds and not clinically relevant minor bleeds. A CRBE was defined as an acute or subacute clinically overt bleed that did not meet the criteria of a major bleed but either lead to hospital admission and/or a physician guided medical or surgical treatment and/or a change in antithrombotic therapy (including interruption or discontinuation of study drug). | 6 month treatment period + 2 week post treatment follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Cardiovascular Death (CVD) With Non Fatal Myocardial Infarction (MI) and Non Haemorrhagic Stroke and All Cause Death (ACD), Non Fatal MI, Severe Recurrent Ischaemia (SRI) and Non Haemorrhagic Stroke During Six Months Treatment | Number of Participants with Composite of Cardiovascular death (CVD) with non fatal myocardial infarction (MI) and non haemorrhagic stroke and All cause death (ACD), non fatal MI, severe recurrent ischaemia (SRI) and non haemorrhagic stroke during six months treatment | 6 month treatment period + 2 week post treatment follow up | 
| Individual Occurrence of Death (Cardiovascular and All-cause), Non-fatal MI, Severe Recurrent Ischaemia and Non-haemorrhagic Stroke During Six Months of Treatment | Number of Participants with individual occurrence of death (cardiovascular and all-cause), non-fatal MI, severe recurrent ischaemia and non-haemorrhagic stroke during six months of treatment. | 6 month treatment period + 2 week post treatment follow up | 
| Number of Participants With Any Reduction of D-dimer Concentration |  | at 1 week and 4 weeks | 
| Change From Baseline in log10 D-dimer After 1 and 4 Weeks | Change from baseline in log10 D-dimer concentration after 1 and 4 weeks of dabigatran etexilate treatment compared to placebo. The standard deviation is the geometric standard deviation. | Baseline and at 1 week and 4 weeks | 
| Number of Participants With Bleeding Events During Total Observation Time | International Society Thrombosis and Haemostasis (ISTH) definition of a major bleed, and clinically relevant minor bleed. A bleeding event was considered as major if it was fatal, was a symptomatic bleeding in a critical area or organ (intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome), or caused a fall in haemoglobin level of ≥2 g/dL (≥1.24 mmol/L), or led to transfusion of ≥2 units of whole blood or red cells. All non major bleeding events were classified as minor bleeds; minor bleeds were subdivided in clinically relevant minor bleeds (CRBE) and not clinically relevant minor bleeds. A CRBE was defined as an acute or subacute clinically overt bleed that did not meet the criteria of a major bleed but either lead to hospital admission and/or a physician guided medical or surgical treatment and/or a change in antithrombotic therapy (including interruption or discontinuation of study drug). | 6 month treatment period + 2 week post treatment follow up | 
| Laboratory Analyses | Number of patients with possible clinically significant abnormalities. Clinically significant abnormalities refers to the increase or decrease from baseline. | 6 month treatment period + 2 week post treatment follow up |