Hemorrhage
Conditions
Brief summary
The primary objective is to demonstrate reversal of the anticoagulant effect of dabigatran in patients treated with dabigatran etexilate who have uncontrolled or life-threatening bleeding requiring urgent intervention, and in patients treated with dabigatran etexilate who require emergency surgery or other invasive procedure. The secondary objectives are to assess the reduction or cessation of bleeding, evaluate the clinical outcomes, safety and the pharmacokinetics of dabigatran in the presence of idarucizumab.
Interventions
DRUGIdarucizumab
Intravenous
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years at screening. * Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. * Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial * Currently taking dabigatran etexilate * They meet the following criteria: * Group A: Overt bleeding judged by the physician to require a reversal agent. OR * Group B: A condition requiring emergency surgery or invasive procedure where adequate hemostasis is required. Emergency is defined as within the following 8 hours.
Exclusion criteria
Group A: * Patients with minor bleeding (e.g. epistaxis, hematuria) who can be managed with standard supportive care. * Patients with no clinical signs of bleeding. * Contraindications to study medication including known hypersensitivity to the drug or its excipients (subjects with hereditary fructose intolerance may react to sorbitol). Group B: * A surgery or procedure which is elective or where the risk of uncontrolled or unmanageable bleeding is low. * Contraindications to study medication including known hypersensitivity to the drug or its excipients (subjects with hereditary fructose intolerance may react to sorbitol).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time | From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period. | Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of ecarin clotting time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 41.26 seconds. |
| Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time | From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period. | Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 35.54 seconds. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1) | Just prior to the second infusion (last infusion) and 10 minutes (min), 30 min, 1 hour (h), 2 h, and 4 h after the end of the second infusion. | Minimum unbound sum dabigatran concentrations since the end of first infusion up to 4 hours after the completion of the last infusion (Cmin,1) is reported. |
| Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT) | From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period. | Maximum reversal of anticoagulation as measured by activated partial thromboplastin time (aPTT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 39.80 seconds. |
| Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT) | From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period. | Maximum reversal of anticoagulation as measured by thrombin time (TT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If calculated reversal is \> 100, it was set to 100. 100% ULN is 14.22 seconds. |
| Numbers of Participants With Any Adverse Events - on Treatment | Since the first infusion up until 5 days after the completion of the second infusion. | Numbers of participants with any adverse events during on treatment period is reported. |
| Numbers of Participants With Any Adverse Events - Including Post Treatment Period | Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days. | Numbers of participants with any adverse events until end of study is reported. |
| Number of Participants With Serious Adverse Events - on Treatment | Since the first infusion up until 5 days after the completion of the second infusion. | Number of participants with Serious adverse events during on treatment period is reported. |
| Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only) | Up to 24 hours after the completion of the second infusion on Day 1 of the treatment period. | Percentage of participants achieving cessation of bleeding within 24 hours after completion of second infusion for Group A is reported. |
| Number of Participants With Drug-related Adverse Events - on Treatment | Since the first infusion up until 5 days after the completion of the second infusion. | Numbers of patients with drug-related adverse events during on treatment period is reported. |
| Number of Participants With Drug-related Adverse Events - Including Post Treatment Period | Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days. | Numbers of patients with drug-related adverse events until end of study is reported. |
| Number of Participants With Immune Reaction Adverse Event - on Treatment | Since the first infusion up until 5 days after the completion of the second infusion. | Number of participants with immune reaction adverse event during on treatment period is reported. |
| Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period | Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days. | Number of participants with immune reaction adverse event until end of study is reported. |
| Number of Participants With Thrombotic Events - on Treatment | Since the first infusion up until 5 days after the completion of the second infusion. | Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) during on treatment period is reported. |
| Number of Participants With Thrombotic Events - Including Post Treatment Period | Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days. | Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) until end of study is reported. |
| Number of Participants With Serious Adverse Events - Including Post Treatment Period | Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days. | Number of participants with Serious adverse events until the end of study is reported. |
| Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery | Up to 24 hours post-surgery. | Number of participants with major bleeding (for Group B only) intra-operatively and up to 24 hours post-surgery per International Society for Thrombosis and Hemostasis (ISTH) classification is reported. |
Countries
China
Participant flow
Recruitment details
This study was to demonstrate the reversal of the anticoagulant effects of dabigatran by intravenous administration of idarucizumab in patients treated with dabigatran etexilate who had uncontrolled bleeding or required emergency surgery or procedures over treatment period of 1 day following by 30 days follow-up.
Pre-assignment details
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding Two vials of 2.5 grams (g) of idarucizumab (BI 655075) (Total: 5g) were administered via intravenous infusions once over a 1-day treatment period. Two vials of idarucizumab were administered no more than 15 minutes apart.
Patients who were taking dabigatran etexilate and had uncontrolled or life-threatening bleeding requiring urgent medical or surgical intervention were included in this group. | 13 |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure Two vials of 2.5 grams (g) of idarucizumab (BI 655075) (Total: 5g) were administered via intravenous infusions once over a 1-day treatment period. Two vials of idarucizumab were administered no more than 15 minutes apart.
Patients included in this group were those who were taking dabigatran etexilate and may not be bleeding, but do require an emergency surgery or other invasive procedure for a condition other than bleeding, where therapeutic anticoagulation with dabigatran etexilate was undesirable. | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Refused to complete follow up | 0 | 1 |
| Overall Study | Reluctant to collect blood and received telephone follow up | 1 | 0 |
Baseline characteristics
| Characteristic | Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Total | Group A - Patients With Uncontrolled or Life-threatening Bleeding |
|---|---|---|---|
| Age, Continuous | 62.8 Years STANDARD_DEVIATION 10.6 | 71.4 Years STANDARD_DEVIATION 13 | 75.4 Years STANDARD_DEVIATION 12.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 19 Participants | 13 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 2 Participants | 10 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 1 / 6 |
| other Total, other adverse events | 13 / 13 | 6 / 6 |
| serious Total, serious adverse events | 7 / 13 | 3 / 6 |
Outcome results
Primary
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of diluted thrombin time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 35.54 seconds.
Time frame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Population: Pharmacodynamic (PD) set (PDS): comprise all patients in the treated set who provided at least one evaluable pre-dose and at least one post-dose observation for PD endpoints or biomarker measures. Only participants with non-missing outcomes are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time | 100.0 Percentage |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time | 100.0 Percentage |
| Total | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time | 100.0 Percentage |
Primary
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time
Maximum reversal of anticoagulant effect of dabigatran based on central laboratory determination of ecarin clotting time is reported. The maximum reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 41.26 seconds.
Time frame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Population: Pharmacodynamic (PD) set (PDS): comprise all patients in the treated set who provided at least one evaluable pre-dose and at least one post-dose observation for PD endpoints or biomarker measures. Only participants with non-missing outcomes are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time | 100.0 Percentage |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time | 100.0 Percentage |
| Total | Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time | 100.0 Percentage |
Secondary
Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT)
Maximum reversal of anticoagulation as measured by activated partial thromboplastin time (aPTT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If the calculated reversal is \> 100, it was set to 100. 100% ULN is 39.80 seconds.
Time frame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Population: Pharmacodynamic (PD) set (PDS): comprise all patients in the treated set who provided at least one evaluable pre-dose and at least one post-dose observation for PD endpoints or biomarker measures. Only participants with non-missing outcomes are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT) | 100 Percentage |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT) | 100 Percentage |
| Total | Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT) | 100 Percentage |
Secondary
Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT)
Maximum reversal of anticoagulation as measured by thrombin time (TT) is reported. The reversal of anticoagulant effect of dabigatran is defined for patients with at least one post-dose coagulation test results and pre-dose result higher than 100% Upper limit of normal (ULN). Maximum reversal is calculated as 100% x (pre-dose value - post-dose value)/(pre-dose value - 100% ULN). If calculated reversal is \> 100, it was set to 100. 100% ULN is 14.22 seconds.
Time frame: From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.
Population: Pharmacodynamic (PD) set (PDS): comprise all patients in the treated set who provided at least one evaluable pre-dose and at least one post-dose observation for PD endpoints or biomarker measures. Only participants with non-missing outcomes are included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT) | 100 Percentage |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT) | 100 Percentage |
| Total | Maximum Reversal of Anticoagulation as Measured by Thrombin Time (TT) | 100 Percentage |
Secondary
Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1)
Minimum unbound sum dabigatran concentrations since the end of first infusion up to 4 hours after the completion of the last infusion (Cmin,1) is reported.
Time frame: Just prior to the second infusion (last infusion) and 10 minutes (min), 30 min, 1 hour (h), 2 h, and 4 h after the end of the second infusion.
Population: Pharmacokinetic (PK) set (PKS): comprise all patients in the TS who provided at least one PK endpoint. The PKS will be used for all PK analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1) | 1 nanogram per milliliter | Geometric Coefficient of Variation 0 |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Minimum Unbound Sum Dabigatran Concentrations Since the End of First Infusion up to 4 Hours After the Completion of the Last Infusion (Cmin,1) | 1 nanogram per milliliter | Geometric Coefficient of Variation 0 |
Secondary
Number of Participants With Drug-related Adverse Events - Including Post Treatment Period
Numbers of patients with drug-related adverse events until end of study is reported.
Time frame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Drug-related Adverse Events - Including Post Treatment Period | 2 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Drug-related Adverse Events - Including Post Treatment Period | 1 Participants |
Secondary
Number of Participants With Drug-related Adverse Events - on Treatment
Numbers of patients with drug-related adverse events during on treatment period is reported.
Time frame: Since the first infusion up until 5 days after the completion of the second infusion.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Drug-related Adverse Events - on Treatment | 2 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Drug-related Adverse Events - on Treatment | 1 Participants |
Secondary
Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period
Number of participants with immune reaction adverse event until end of study is reported.
Time frame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period | 3 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Immune Reaction Adverse Event - Including Post Treatment Period | 0 Participants |
Secondary
Number of Participants With Immune Reaction Adverse Event - on Treatment
Number of participants with immune reaction adverse event during on treatment period is reported.
Time frame: Since the first infusion up until 5 days after the completion of the second infusion.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Immune Reaction Adverse Event - on Treatment | 3 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Immune Reaction Adverse Event - on Treatment | 0 Participants |
Secondary
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery
Number of participants with major bleeding (for Group B only) intra-operatively and up to 24 hours post-surgery per International Society for Thrombosis and Hemostasis (ISTH) classification is reported.
Time frame: Up to 24 hours post-surgery.
Population: Treated set (TS): include all patients who are administered with idarucizumab. This analysis only included patients not bleeding but requiring emergency surgery or invasive procedure (Group B).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery | Minor | 0 Participants |
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery | Major | 1 Participants |
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery | Major, Life -Threatening or Fatal | 0 Participants |
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery | Not assessable | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events - Including Post Treatment Period
Number of participants with Serious adverse events until the end of study is reported.
Time frame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Serious Adverse Events - Including Post Treatment Period | 7 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Serious Adverse Events - Including Post Treatment Period | 3 Participants |
Secondary
Number of Participants With Serious Adverse Events - on Treatment
Number of participants with Serious adverse events during on treatment period is reported.
Time frame: Since the first infusion up until 5 days after the completion of the second infusion.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Serious Adverse Events - on Treatment | 3 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Serious Adverse Events - on Treatment | 1 Participants |
Secondary
Number of Participants With Thrombotic Events - Including Post Treatment Period
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) until end of study is reported.
Time frame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Thrombotic Events - Including Post Treatment Period | 2 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Thrombotic Events - Including Post Treatment Period | 3 Participants |
Secondary
Number of Participants With Thrombotic Events - on Treatment
Number of participants with thrombotic events (ischemic stroke, myocardial infarction, pulmonary embolism, deep vein thrombosis, systemic embolism) during on treatment period is reported.
Time frame: Since the first infusion up until 5 days after the completion of the second infusion.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Number of Participants With Thrombotic Events - on Treatment | 1 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Number of Participants With Thrombotic Events - on Treatment | 1 Participants |
Secondary
Numbers of Participants With Any Adverse Events - Including Post Treatment Period
Numbers of participants with any adverse events until end of study is reported.
Time frame: Since informed consent up to 30 days (± 7 days) after the completion of the second infusion, up to 37 days.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Numbers of Participants With Any Adverse Events - Including Post Treatment Period | 13 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Numbers of Participants With Any Adverse Events - Including Post Treatment Period | 6 Participants |
Secondary
Numbers of Participants With Any Adverse Events - on Treatment
Numbers of participants with any adverse events during on treatment period is reported.
Time frame: Since the first infusion up until 5 days after the completion of the second infusion.
Population: Treated set (TS): include all patients who are administered with idarucizumab.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Numbers of Participants With Any Adverse Events - on Treatment | 11 Participants |
| Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure | Numbers of Participants With Any Adverse Events - on Treatment | 6 Participants |
Secondary
Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only)
Percentage of participants achieving cessation of bleeding within 24 hours after completion of second infusion for Group A is reported.
Time frame: Up to 24 hours after the completion of the second infusion on Day 1 of the treatment period.
Population: Treated set (TS): include all patients who are administered with idarucizumab. Patients with no evaluable post-baseline bleeding assessment are excluded. This analysis only included patients with uncontrolled or life-threatening bleeding, and non-Intracranial Hemorrhage (non-ICH) in Group A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A - Patients With Uncontrolled or Life-threatening Bleeding | Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only) | 55.6 Percentage of participants |