Thromboembolism
Conditions
Brief summary
The purpose of this trial is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin as needed (pro re nata - prn) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic venous thromboembolism (VTE), following initial treatment (5-10 days) with a parenteral anticoagulant approved for this indication. This trial aims to demonstrate non-inferiority of dabigatran compared with warfarin in patients with acute symptomatic VTE. After achieving non-inferiority, this trial also aims to establish superiority (by means of hierarchical tests) of dabigatran over warfarin.
Interventions
DRUGdabigatran etexilate 150 mg
twice daily
DRUGwarfarin (INR 2-3)
prn to maintain INR (2-3)
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Acute deep vein thrombosis (DVT) of the leg involving proximal veins, and/or pulmonary embolism (PE) iin patients for whom at least 6 months of anticoagulant therapy is considered appropriate 2. Male or female, being 18 years of age or older 3. Written informed consent for study participation
Exclusion criteria
1. Overt symptoms of VTE for longer than 2 weeks prior to enrolment 2. PE satisfying at least one of the following criteria: Haemodynamic instability, embolectomy is indicated or performed, thrombolytic therapy is indicated or performed, or suspected source of PE is other than the legs 3. Actual or anticipated use of vena cava filter 4. Contraindications to anticoagulant therapy 5. Patients who in the investigators opinion should not be treated with warfarin 6. Allergy to heparins or other alternate approved therapy used for initial treatment, warfarin or dabigatran, or to one of the excipients included in these medications 7. Patients who in the investigators judgement are perceived as having an excessive risk of bleeding 8. Known anaemia 9. Need of anticoagulant treatment for disorders other than VTE 10. Recent unstable cardiovascular disease 11. Elevated AST or ALT \> 2x ULN 12. Liver disease expected to have any potential impact on survival 13. Patients who have developed transaminase elevations upon exposure to ximelagatran 14. Severe renal impairment 15. Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception 16. Participation in another clinical trial with an investigational drug during the last 30 days or previous participation in this study 17. Patients considered unsuitable for inclusion by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE | For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Recurrent Symptomatic DVT | 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. | Symptomatic DVT which occured from randomisation to end of post treatment period. 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 | 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. | Symptomatic non-fatal PE which occured from randomisation to end of post treatment period. 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 | 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. | VTE - related deaths which occured from randomisation to end of post treatment period. 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 VTE and All Deaths | 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. | VTE or any death which occured from randomisation to end of post treatment period. 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 Bleeding Events | From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) | Major bleeding events (MBE) were defined as * Fatal bleeding * Symptomatic bleeding in a critical area or organ * 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 Clinically-relevant bleeding events (CRBE) was defined as * spontaneous skin hematoma \>=25 cm² * spontaneous nose bleed \>5 min * macroscopic hematuria spontaneous or \>24 hours if associated with an intervention * spontaneous rectal bleeding (more than spotting on toilet paper) * gingival bleeding \>5 min * leading to hospitalisation and / or requiring surgical treatment * leading to a transfusion of \<2 units of whole blood or red cells * any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above. |
| Number of Participants With Acute Coronary Syndrome (ACS) | From first intake of study drug to end of study conduct | Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group. 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. |
| Laboratory Analyses | From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) | Frequency of patients with possible clinically significant abnormalities. |
| Number of Participants Who Died (Any Cause) | 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. | Any deaths which occured from randomisation to end of post treatment period. 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Mexico, Netherlands, New Zealand, Norway, Portugal, Russia, Slovakia, South Africa, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
There were 2564 patients enrolled/randomised in this trial but only 2539 started treatment
Participants by arm
| Arm | Count |
|---|---|
| Dabigatran 150 mg bid (twice daily) oral | 1,273 |
| Warfarin PRN to maintain an INR of 2.0-3.0 | 1,266 |
| Total | 2,539 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 47 | 40 |
| Overall Study | Lost to Follow-up | 16 | 11 |
| Overall Study | Other | 3 | 1 |
| Overall Study | Protocol Violation | 13 | 20 |
| Overall Study | Withdrawal by Subject | 22 | 25 |
Baseline characteristics
| Characteristic | Dabigatran 150 mg | Total | Warfarin |
|---|---|---|---|
| Acute symptomatic DVT of the leg and/or PE as assessed by investigator No PE and no DVT | 2 participants | 4 participants | 2 participants |
| Acute symptomatic DVT of the leg and/or PE as assessed by investigator Symptomatic DVT | 880 participants | 1749 participants | 869 participants |
| Acute symptomatic DVT of the leg and/or PE as assessed by investigator Symptomatic PE | 270 participants | 541 participants | 271 participants |
| Acute symptomatic DVT of the leg and/or PE as assessed by investigator Symptomatic PE and symptomatic DVT | 121 participants | 245 participants | 124 participants |
| Age, Continuous | 55.0 Year STANDARD_DEVIATION 15.8 | 54.7 Year STANDARD_DEVIATION 16 | 54.4 Year STANDARD_DEVIATION 16.2 |
| Sex: Female, Male Female | 535 Participants | 1055 Participants | 520 Participants |
| Sex: Female, Male Male | 738 Participants | 1484 Participants | 746 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 163 / 1,273 | 209 / 1,266 |
| serious Total, serious adverse events | 165 / 1,273 | 150 / 1,266 |
Outcome results
Primary
Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE
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.
Time frame: For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180)
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE | Participants with event (up to day 180) | 30 Participants |
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE | Participants with event (up to end of ptp) | 34 Participants |
| Warfarin | Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE | Participants with event (up to day 180) | 27 Participants |
| Warfarin | Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE | Participants with event (up to end of ptp) | 32 Participants |
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the primary endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: <0.000195% CI: [0.65, 1.7]Regression, Cox
Comparison: Risk difference vs. Warfarin for Proportion of patients with VTE or death related to VTE at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: <0.000195% CI: [-0.8, 1.5]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and the day 180). The time to first occurrence of the primary endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.95% CI: [0.65, 1.84]Regression, Cox
Secondary
Laboratory Analyses
Frequency of patients with possible clinically significant abnormalities.
Time frame: From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug)
Population: Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Laboratory Analyses | AST decrease | 0 participants |
| Dabigatran 150 mg | Laboratory Analyses | ALT increase | 26 participants |
| Dabigatran 150 mg | Laboratory Analyses | AST increase | 21 participants |
| Dabigatran 150 mg | Laboratory Analyses | ALT decrease | 0 participants |
| Dabigatran 150 mg | Laboratory Analyses | Bilirubin increase | 7 participants |
| Dabigatran 150 mg | Laboratory Analyses | Bilirubin decrease | 0 participants |
| Warfarin | Laboratory Analyses | Bilirubin increase | 13 participants |
| Warfarin | Laboratory Analyses | AST decrease | 0 participants |
| Warfarin | Laboratory Analyses | ALT decrease | 0 participants |
| Warfarin | Laboratory Analyses | ALT increase | 38 participants |
| Warfarin | Laboratory Analyses | Bilirubin decrease | 0 participants |
| Warfarin | Laboratory Analyses | AST increase | 22 participants |
Secondary
Number of Participants Who Died (Any Cause)
Any deaths which occured from randomisation to end of post treatment period. 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.
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.
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants Who Died (Any Cause) | Participants with event (up to day 180) | 21 participants |
| Dabigatran 150 mg | Number of Participants Who Died (Any Cause) | Participants with event (up to end of ptp) | 25 participants |
| Warfarin | Number of Participants Who Died (Any Cause) | Participants with event (up to day 180) | 21 participants |
| Warfarin | Number of Participants Who Died (Any Cause) | Participants with event (up to end of ptp) | 25 participants |
Comparison: Risk difference at 6 months vs. Warfarin for Proportion of patients who died from any cause. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: 0.801895% CI: [-1, 0.8]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.820395% CI: [0.54, 1.63]Regression, Cox
Secondary
Number of Participants Who Died Due to VTE
VTE - related deaths which occured from randomisation to end of post treatment period. 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.
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.
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants Who Died Due to VTE | Participants with event (up to end of ptp) | 1 participants |
| Dabigatran 150 mg | Number of Participants Who Died Due to VTE | Participants with event (up to day 180) | 1 participants |
| Warfarin | Number of Participants Who Died Due to VTE | Participants with event (up to end of ptp) | 3 participants |
| Warfarin | Number of Participants Who Died Due to VTE | Participants with event (up to day 180) | 3 participants |
Comparison: Risk difference at 6 months vs. Warfarin for Proportion of patients who died due to VTE . Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: 0.532795% CI: [-1.2, 0.6]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.333295% CI: [0.03, 3.15]Regression, Cox
Secondary
Number of Participants With Acute Coronary Syndrome (ACS)
Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group. 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.
Time frame: From first intake of study drug to end of study conduct
Population: Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Acute Coronary Syndrome (ACS) | During intake of active study drug | 5 participants |
| Dabigatran 150 mg | Number of Participants With Acute Coronary Syndrome (ACS) | After stopping active study drug | 4 participants |
| Dabigatran 150 mg | Number of Participants With Acute Coronary Syndrome (ACS) | Before/without intake of active study drug | 2 participants |
| Warfarin | Number of Participants With Acute Coronary Syndrome (ACS) | During intake of active study drug | 3 participants |
| Warfarin | Number of Participants With Acute Coronary Syndrome (ACS) | After stopping active study drug | 2 participants |
| Warfarin | Number of Participants With Acute Coronary Syndrome (ACS) | Before/without intake of active study drug | 0 participants |
Secondary
Number of Participants With Bleeding Events
Major bleeding events (MBE) were defined as * Fatal bleeding * Symptomatic bleeding in a critical area or organ * 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 Clinically-relevant bleeding events (CRBE) was defined as * spontaneous skin hematoma \>=25 cm² * spontaneous nose bleed \>5 min * macroscopic hematuria spontaneous or \>24 hours if associated with an intervention * spontaneous rectal bleeding (more than spotting on toilet paper) * gingival bleeding \>5 min * leading to hospitalisation and / or requiring surgical treatment * leading to a transfusion of \<2 units of whole blood or red cells * any other bleeding event considered clinically relevant by the investigator Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.
Time frame: From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug)
Population: Treated set (TS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as treated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Bleeding Events | Major bleeding events | 20 participants |
| Dabigatran 150 mg | Number of Participants With Bleeding Events | MBE and/or CRBE | 71 participants |
| Dabigatran 150 mg | Number of Participants With Bleeding Events | Any bleeding events | 207 participants |
| Warfarin | Number of Participants With Bleeding Events | MBE and/or CRBE | 111 participants |
| Warfarin | Number of Participants With Bleeding Events | Major bleeding events | 24 participants |
| Warfarin | Number of Participants With Bleeding Events | Any bleeding events | 280 participants |
Comparison: Hazard ratio vs. Warfarin for the category major bleeding events (events occurring between 1st intake of study drug and last intake of study drug + 6 days). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.506395% CI: [0.45, 1.48]Regression, Cox
Comparison: Hazard ratio vs. Warfarin for the category of any bleeding events (events occurring between 1st intake of study drug and last intake of study drug + 6 days). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.000295% CI: [0.59, 0.85]Regression, Cox
Secondary
Number of Participants With Recurrent Symptomatic DVT
Symptomatic DVT which occured from randomisation to end of post treatment period. 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.
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.
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic DVT | Participants with event (up to day 180) | 16 participants |
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic DVT | Participants with event (up to end of ptp) | 17 participants |
| Warfarin | Number of Participants With Recurrent Symptomatic DVT | Participants with event (up to day 180) | 18 participants |
| Warfarin | Number of Participants With Recurrent Symptomatic DVT | Participants with event (up to end of ptp) | 22 participants |
Comparison: Risk difference vs. Warfarin for Proportion of patients with symptomatic DVT at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: 0.646695% CI: [-1.1, 0.7]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.38595% CI: [0.4, 1.42]Regression, Cox
Secondary
Number of Participants With Recurrent Symptomatic Non-fatal PE
Symptomatic non-fatal PE which occured from randomisation to end of post treatment period. 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.
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.
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic Non-fatal PE | Participants with event (up to day 180) | 13 participants |
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic Non-fatal PE | Participants with event (up to end of ptp) | 16 participants |
| Warfarin | Number of Participants With Recurrent Symptomatic Non-fatal PE | Participants with event (up to day 180) | 7 participants |
| Warfarin | Number of Participants With Recurrent Symptomatic Non-fatal PE | Participants with event (up to end of ptp) | 8 participants |
Comparison: Risk difference vs. Warfarin for Proportion of patients with symptomatic non-fatal PE at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: 0.298195% CI: [-0.3, 1]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.109295% CI: [0.86, 4.68]Regression, Cox
Secondary
Number of Participants With Recurrent Symptomatic VTE and All Deaths
VTE or any death which occured from randomisation to end of post treatment period. 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.
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.
Population: Full analysis set (FAS): consisted of all randomised patients who were documented to have taken at least one dose of study drug. Patients were assigned to the treatment groups as randomised, i.e. regardless of the actual medication taken.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic VTE and All Deaths | Participants with event (up to day 180) | 48 Participants |
| Dabigatran 150 mg | Number of Participants With Recurrent Symptomatic VTE and All Deaths | Participants with event (up to end of ptp) | 55 Participants |
| Warfarin | Number of Participants With Recurrent Symptomatic VTE and All Deaths | Participants with event (up to day 180) | 44 Participants |
| Warfarin | Number of Participants With Recurrent Symptomatic VTE and All Deaths | Participants with event (up to end of ptp) | 53 Participants |
Comparison: Risk difference vs. Warfarin for Proportion of patients with VTE or death at 6 months. Point estimate and 95% CI for the overall risk difference obtained based on the Kaplan Meier (KM) estimates at 6 months (180 days) after adjusting for the stratification factors active cancer at baseline and symptomatic PE at baseline.p-value: 0.62295% CI: [-1, 1.7]Kaplan Meier weighted estimates
Comparison: Hazard ratio vs. Warfarin (events occurring between randomisation and end of post treatment period). The time to first occurrence of the endpoint was compared between treatment groups using the Cox proportional hazards (PH) model, including the factors treatment, active cancer at baseline, symptomatic PE at baseline, and the interaction between active cancer and symptomatic PE.p-value: 0.984495% CI: [0.69, 1.46]Regression, Cox