Trial Outcomes & Findings for Reversal Dabigatran Anticoagulant Effect With Idarucizumab (NCT NCT02815670)

Results Overview

Number of participants with drug-related adverse events (AEs) including immune reactions and all cause mortality during the trial.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1 participants

Primary outcome timeframe

From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days

Results posted on

2020-04-14

Participant Flow

An open-label, uncontrolled case series trial, with a single treatment arm of idarucizumab in patients with venous thromboembolism treated with dabigatran etexilate in ongoing Boehringer Ingelheim pediatric clinical trials (1160.106 and 1160.108). Treatment period was around 1 day followed by 29 days of safety follow-up period.

All subjects were screened for eligibility to participants in the trial. Subjects attended specialist sites which would then ensure that they met all strictly implemented inclusion/exclusion criteria. Subjects were not to be assigned to treatment groups if any one of the specific entry criteria were violated.

Participant milestones

Participant milestones
Measure	Idarucizumab 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Overall Study STARTED	1
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Idarucizumab 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Overall Study Prematurely discontinued of the trial	1

Baseline Characteristics

Reversal Dabigatran Anticoagulant Effect With Idarucizumab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Age, Continuous	NA Years STANDARD_DEVIATION NA • n=5 Participants
Sex: Female, Male Female	NA Participants n=5 Participants
Sex: Female, Male Male	NA Participants n=5 Participants
Race/Ethnicity, Customized	NA Participants n=5 Participants

PRIMARY outcome

Timeframe: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days

Population: Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, and antidrug antibodies (ADA).

Number of participants with drug-related adverse events (AEs) including immune reactions and all cause mortality during the trial.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Number of Participants With Drug-related Adverse Events (AEs)	0 Participants

SECONDARY outcome

Timeframe: At immediately prior to administration of vial 1 of Idarucizumab and 30 minutes (min) post vial 2 administration.

Population: Pharmacodynamic (PD) set (PDS): comprising all patients in the TS who provided at least 1 evaluable pre-dose and at least 1 post-dose observation for PD endpoints or biomarker measures. The PDS was used for the PD endpoint analyses. Note that for different PD endpoints or biomarkers, the number of evaluable patients could differ between endpoints.

Percent change of coagulation time for diluted thrombin time (dTT) and ecarin clotting time (ECT) at 30 minutes (min) post-dose compared with pre-dose. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Percent Change of Coagulation Time for Diluted Thrombin Time (dTT) and Ecarin Clotting Time (ECT) at 30 Minutes Post-dose Compared With Pre-dose Diluted thrombin time (dTT)	-46.3 Percentage of time in seconds
Percent Change of Coagulation Time for Diluted Thrombin Time (dTT) and Ecarin Clotting Time (ECT) at 30 Minutes Post-dose Compared With Pre-dose Ecarin clotting time (ECT)	-67.8 Percentage of time in seconds

SECONDARY outcome

Timeframe: From end of vial 2 of Idarucizumab up to 24h.

Population: Pharmacodynamic (PD) set (PDS): comprising all patients in the TS who provided at least 1 evaluable pre-dose and at least 1 post-dose observation for PD endpoints or biomarker measures. The PDS was used for the PD endpoint analyses. Note that for different PD endpoints or biomarkers, the number of evaluable patients could differ between endpoints.

Idarucizumab administration resulted in normalisation of dTT and ECT. Time to achieve reversal of anticoagulant effect of dabigatran based on the coagulation time for dTT and ECT, at any time point from the end of the second injection (vial 2) up to 24 hours (h). Reversal of the dabigatran effect at time t was defined as the 100 percent (%) \*(pre-dose coagulation time - post-dose coagulation time at time t)/(pre-dose coagulation test - upper limit of normal). Values equal to or higher than 100% were interpreted as reversal. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of Idarucizumab and post-dose at 30min, 4h, 12h and 24h.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Time to Achieve Reversal of the Dabigatran Effect (Based on the Coagulation Time for dTT and ECT)	30 Minutes

SECONDARY outcome

Timeframe: From end of vial 2 of Idarucizumab up to 24h.

Population: Pharmacodynamic (PD) set (PDS): comprising all patients in the TS who provided at least 1 evaluable pre-dose and at least 1 post-dose observation for PD endpoints or biomarker measures. The PDS was used for the PD endpoint analyses. Note that for different PD endpoints or biomarkers, the number of evaluable patients could differ between endpoints.

Duration of reversal, defined as the time period a patient remained completely reversed based on dTT and ECT, up to 24 hours post-dose or restarting the treatment of anticoagulation. Central blood sampling for dTT, ECT were to occur immediately prior to administration of each vial of idarucizumab and post-dose at 30min, 4h, 12h and 24h.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Duration of Reversal of the Dabigatran Effect Sustained up to 24 Hours Post-dose (Based on the Coagulation Time for dTT and ECT)	23.5 Hours

SECONDARY outcome

Timeframe: From vial 1 of Idarucizumab through vial 2 of Idarucizumab, up to 24h 30min.

Population: Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, as well as ADA.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Number of Participants With Cessation of Bleeding	1 Participants

SECONDARY outcome

Timeframe: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days

Population: Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, as well as ADA.

Numbers of participants whose bleeding had stopped, reduced, unchanged, worsened or not applicable during the trial were characterized.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Number of Participants Per Bleeding Status During the Trial Stopped	1 Participants
Number of Participants Per Bleeding Status During the Trial Reduced	0 Participants
Number of Participants Per Bleeding Status During the Trial Unchanged	0 Participants
Number of Participants Per Bleeding Status During the Trial Worsened	0 Participants
Number of Participants Per Bleeding Status During the Trial Not applicable	0 Participants

SECONDARY outcome

Timeframe: From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days

Population: Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, as well as ADA.

Number of participants with clinical conditions (trauma, surgery and use of antiplatelet) contributing to bleeding during the trial were characterized.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial Trauma	1 Participants
Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial Surgery	0 Participants
Number of Participants With Clinical Conditions Contributing to Bleeding During the Trial Use of antiplatelet	0 Participants

SECONDARY outcome

Timeframe: At day 25 post vial 2 of Idarucizumab administration, up to 1 day

Population: Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, as well as ADA.

Outcome measures

Outcome measures
Measure	Idarucizumab n=1 Participants 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Number of Participants Developing Treatment-emergent Antidrug Antibodies (ADA) With Cross Reactivity to Idarucizumab	0 Participants

Adverse Events

Idarucizumab

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Idarucizumab n=1 participants at risk 2.5 gram (g) per 50 milliliter (mL) vial of Idarucizuma was administrated via intravenous injection (vial 1) with (in order of preference): a 5 minutes (min) infusion with an infusion pump, a 10 to 15 min drip, or intravenous push with a syringe followed by another injection (vial 2) of same dosage of Idarucizumab for participants who were treated with dabigatran and had uncontrolled or life threatening bleeding that required urgent medical or surgical intervention or who required emergency surgery/urgent procedures where adequate haemostasis was required (total dosage: up to 5g based on the weight of participant). Two equal injection parts were administered no more than 15 min apart. The time between start of injection of the first vial and end of the second vial was 22 min followed by 24 hours post-dose observation period.
Blood and lymphatic system disorders Thrombocytopenia	100.0% 1/1 • From vial 1 of Idarucizumab until prematurely discontinued of the trial, up to 25 days Treated set (TS): including all patients who received any dose of Idarucizumab. The TS was used to assess safety, clinical endpoints, demographics and baseline characteristics, concomitant diagnosis/therapy and medical history, and antidrug antibodies (ADA).

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER