Reversal of Dabigatran With Prothrombin Complex Concentrate

NCT ID: NCT02463591

Last Updated: 2016-05-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2016-12-31

Brief Summary

The purpose of this study is to investigate whether Prothrombin Complex Concentrate (PCC) is effective in reversing the anticoagulant effect of Dabigatran, as assessed by two modified skin-bleeding tests.

Detailed Description

There is currently no treatment widely available for immediate reversal of Dabigatran anticoagulant effects, e.g. in case of major bleeding or when emergency surgery or invasive procedures are indicated.

Treatment with prothrombin complex concentrate (PCC) seems effective in reducing blood loss in animal models, but previous studies in humans have failed to show an effect on blood coagulation parameters. Recently, two novel methods of skin blood loss, one called "shed blood" and another "washed blood" were able to measure effects of anticoagulation, either as the inhibition of fibrin formation at the wound site by measuring Fibrinopeptide A (FPA) or as elevated blood loss, respectively, after oral administration of Dabigatran in healthy volunteers.

The investigators hypothesise that the shed/washed blood methods are able to measure Dabigatran reversal following administration of PCC (Beriplex).

The study will be performed as a randomised double blind cross-over study and 12 healthy human male subjects will be enrolled. Subjects will take Dabigatran 300 mg b.i.d. on day -2, -1 and 0. After the fifth dose (on day 0), subjects will be randomised to receive Beriplex (50 IU/kg) or a similar volume of saline as a single bolus dose i.v. over 20 minutes. After a 10 day minimum wash-out period this procedure will be repeated, and the alternative treatment (Saline or Beriplex) is administered.

The Shed / Washed Blood measurements will be performed at different time points before and after starting oral anticoagulants and before and after administration of Beriplex/Saline.

In addition to the Shed / Washed blood tests, several ex vivo standard coagulation tests will be performed. These include: activated partial thromboplastin time (aPTT), prothrombin time (PT), diluted thrombin time (DTT/Hemoclot), Dabigatran plasma levels (using liquid chromatography-tandem mass spectrometry (LC-MS/MS)), endogenous thrombin generation (ETG) and pre and post factor II, VII, IX and X.

Conditions

Drug Action Reversal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Beriplex 50 IU/Kg

Cross over design: After therapy with Dabigatran Etexilate 300mg BID for 2.5 days, subjects will receive a single dose of Beriplex 50 IU/Kg. After a 10 day minimum wash-out period subjects will receive the alternative treatment (Placebo).

Group Type: EXPERIMENTAL

Beriplex

Intervention Type: DRUG

Beriplex 50 IU/Kg i.v. , single dose.

Placebo

Cross over design: After therapy with Dabigatran Etexilate 300mg BID for 2.5 days, subjects will receive a single dose of Placebo identically in appearance to Beriplex 50 IU/Kg. After a 10 day minimum wash-out period subjects will receive the alternative treatment (Beriplex).

Group Type: PLACEBO_COMPARATOR

Beriplex

Intervention Type: DRUG

Beriplex 50 IU/Kg i.v. , single dose.

Interventions

Beriplex

Beriplex 50 IU/Kg i.v. , single dose.

Intervention Type: DRUG

Other Intervention Names

Prothrombin Complex Concentrate; RVG 101094; B02BD01

Eligibility Criteria

Inclusion Criteria

• Healthy males
• Age between 18 and 50 years
• Weight <100 kg
• Signed informed consent
• eGFR ≥ 80ml/min*1.73m2

Exclusion Criteria

• History of allergic reaction to blood products
• Current participation in any other investigational drug study or within the past 30 days
• Increased bleeding tendency or history of thrombosis
• Anticoagulant medication, platelet aggregation inhibitors or NSAIDs
• Use of any medication 14 days before start of dabigatran intake

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: collaborator

CSL Behring

INDUSTRY

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

Pieter W. Kamphuisen, MD PhD

Prof. dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pieter Willem Kamphuisen, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

University Medical Centre

Groningen, Provincie Groningen, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Alexander C Stehouwer, MD

Role: CONTACT

a.c.stehouwer@umcg.nl

0031503610116

Hilde Hop, MD

Role: CONTACT

h.hop@umcg.nl

0031503610116

Facility Contacts

A C Stehouwer, MD

Role: primary

a.c.stehouwer@umcg.nl

0031503610116

H Hop, MD

Role: backup

h.hop@umcg.nl

0031503610116

References

Wolzt M, Eder M, Weltermann A, Entlicher J, Eichler HG, Kyrle PA. Comparison of the effects of different low molecular weight heparins on the hemostatic system activation in vivo in man. Thromb Haemost. 1997 Aug;78(2):876-9.

Reference Type: BACKGROUND

PMID: 9268188 (View on PubMed)

Other Identifiers

2014-002204-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BI 1160.203

Identifier Type: -

Identifier Source: org_study_id