Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)

• Number of Participants With Recurrent Symptomatic VTE and All Deaths [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
  VTE or any death which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
• Number of Participants With Recurrent Symptomatic DVT [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
  Symptomatic DVT which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
• Number of Participants With Recurrent Symptomatic Non-fatal PE [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180). For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
  Symptomatic non-fatal PE which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
• Number of Participants Who Died Due to VTE [ Time Frame: From randomisation to 6 months (up to day 180) and to end of ptp (planned to be up to day 224) ] [ Designated as safety issue: No ]
  VTE - related deaths which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
• Number of Participants Who Died (Any Cause) [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ] [ Designated as safety issue: No ]
  Any deaths which occured from randomisation to end of ptp. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.
• Number of Participants With Major Bleeding Events (MBE) [ Time Frame: From first intake of study drug to last intake of study drug + 6 days ] [ Designated as safety issue: Yes ]

  MBEs defined as per the recommendations of the International Society on Thrombosis and Haemostasis. A bleeding event was categorised as an MBE (adjudicated by the independent central assessment committee) if it fulfilled at least one of the following criteria:

  ââ " Fatal bleeding, ââ " Symptomatic bleeding in a critical area or organ, ââ " Bleeding causing a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells.

The general aim of this study is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin Pro re nata (As needed/PRN) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic VTE.

The primary objective is to investigate the efficacy of dabigatran compared to warfarin during the 6 month treatment period. The investigation of other selected efficacy aspects and safety are regarded as secondary objective of this trial.

• Drug: Warfarin
  PRN (to maintain a target INR of 2.0-3.0)
• Drug: Dabigatran etexilate
  150mg bid

• Experimental: Dabigatran etexilate (150mg bid)
  Patients will receive 1 capsule containing 150 mg dabigatran etexilate/matching placebo twice daily
  Intervention: Drug: Dabigatran etexilate
• Active Comparator: Warfarin (INR 2.0-3.0)
  Patients will receive tablets PRN warfarin/matching placebo to maintain a target INR of 2.0-3.0
  Intervention: Drug: Warfarin

Inclusion criteria:

• Acute symptomatic uni- or bilateral Deep Vein Thrombosis (DVT) of the leg involving proximal veins, and/or Pulmonary Embolism (PE)
• Male or female, being 18 years of age or older
• Written informed consent for study participation

Exclusion criteria:

• Persistent symptoms of VTE
• PE requiring urgent intervention
• Use of vena cava filter
• Contraindications to anticoagulant therapy
• Allergy to study medications
• Elevated Aspartate-aminotransferase (AST) or Alanine-aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) or known liver disease expected to have an impact on survival
• Severe renal impairment
• Patients considered unsuitable for inclusion