Trial Outcomes & Findings for This Study Looks at the Effects of Idarucizumab in Patients Who Take Dabigatran and Need Emergency Surgery or Are Bleeding (NCT NCT03343704)

Last Updated: 2025-02-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

19 participants

Primary outcome timeframe

From the end of first infusion up to 4 hours after the completion of the second infusion on Day 1 of the treatment period.

Results posted on

2025-02-25

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	13	6
Overall Study COMPLETED	12	4
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Refused to complete follow up	0	1
Overall Study Death	0	1
Overall Study Reluctant to collect blood and received telephone follow up	1	0

Baseline Characteristics

This Study Looks at the Effects of Idarucizumab in Patients Who Take Dabigatran and Need Emergency Surgery or Are Bleeding

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=13 Participants 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.	Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure n=6 Participants 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.	Total n=19 Participants Total of all reporting groups
Age, Continuous	75.4 Years STANDARD_DEVIATION 12.3 • n=5 Participants	62.8 Years STANDARD_DEVIATION 10.6 • n=7 Participants	71.4 Years STANDARD_DEVIATION 13.0 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=6 Participants 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.	Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure n=4 Participants 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.	Total n=10 Participants All participants in Group A or B were included in this group.
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Ecarin Clotting Time	100.0 Percentage Interval 100.0 to 100.0	100.0 Percentage Interval 96.8 to 100.0	100.0 Percentage Interval 100.0 to 100.0

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=5 Participants 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.	Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure n=4 Participants 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.	Total n=9 Participants All participants in Group A or B were included in this group.
Maximum Reversal of Anticoagulant Effect of Dabigatran Based on Central Laboratory Determination of Diluted Thrombin Time	100.0 Percentage Interval 100.0 to 100.0	100.0 Percentage Interval 100.0 to 100.0	100.0 Percentage Interval 100.0 to 100.0

SECONDARY outcome

Timeframe: 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.

Percentage of participants achieving cessation of bleeding within 24 hours after completion of second infusion for Group A is reported.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=9 Participants 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.	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.	Total All participants in Group A or B were included in this group.
Percentage of Participants Achieving Cessation of Bleeding Within 24 Hours After Completion of Second Infusion (for Group A Only)	55.6 Percentage of participants	—	—

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=6 Participants 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.	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.	Total All participants in Group A or B were included in this group.
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery Minor	0 Participants	—	—
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery Major	1 Participants	—	—
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	—	—
Number of Participants With Major Bleeding (for Group B Only) Intra-operatively and up to 24 Hours Post-surgery Not assessable	0 Participants	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=6 Participants 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.	Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure n=4 Participants 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.	Total All participants in Group A or B were included in this group.
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	1 nanogram per milliliter Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Group A - Patients With Uncontrolled or Life-threatening Bleeding n=5 Participants 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.	Group B - Patients Not Bleeding But Requiring Emergency Surgery or Invasive Procedure n=4 Participants 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.	Total n=9 Participants All participants in Group A or B were included in this group.
Maximum Reversal of Anticoagulation as Measured by Activated Partial Thromboplastin Time (aPTT)	100 Percentage Interval 67.9 to 100.0	100 Percentage Interval 98.3 to 100.0	100 Percentage Interval 98.3 to 100.0

SECONDARY outcome

Timeframe: 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.