Reversal of Dabigatran With Prothrombin Complex Concentrate
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|ClinicalTrials.gov Identifier: NCT02463591|
Recruitment Status : Unknown
Verified May 2016 by Pieter W. Kamphuisen, MD PhD, University Medical Center Groningen.
Recruitment status was: Recruiting
First Posted : June 4, 2015
Last Update Posted : May 12, 2016
|Condition or disease||Intervention/treatment||Phase|
|Drug Action Reversal||Drug: Beriplex||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Reversal of Anticoagulant Effect of Dabigatran® by Prothrombin Complex Concentrate (Beriplex®), Assessed With a Novel Method of Blood Loss Measurement|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||July 2016|
|Estimated Study Completion Date :||December 2016|
Experimental: 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).
Beriplex 50 IU/Kg i.v. , single dose.
Placebo Comparator: 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).
Beriplex 50 IU/Kg i.v. , single dose.
- Inhibition of the anticoagulant effect of Dabigatran, assessed by the "shed and washed blood" methods [ Time Frame: Before Dabigatran (Baseline, T= day-2), After Dabigatran / Before PCC (T= day 0), After Dabigatran / After PCC (T=40 min.), After Dabigatran / After PCC (T=360 min.) ]
The Shed blood test allows assessment of thrombin activity and subsequent fibrinogen conversion to fibrin in vivo by measuring fibrinopeptide A (FPA) generation. A standardized wound, using a disposable device (Surgicutt® Adult) is made on the volar surface of the forearm, from which blood is collected during 4 minutes. The total amount of shed blood is measured in addition to Fibrinopeptide A levels. FPA levels are compared to FPA levels in systemic venous samples collected at corresponding timepoints.
The washed blood test measures both the time until bleeding stops and sensitively measures small volumes of blood loss as area under the curve (AUC).
- Change in Standard Coagulation Assays before / after Dabigatran and before / after PCC. [ Time Frame: Before Dabigatran (Baseline, T= day-2), After Dabigatran / Before PCC (T= day 0), After Dabigatran / After PCC (T=20 min., T=40 min., T=60 min., T=120 min., T=240 min., T=360 min. ]aPTT, PT, Diluted Thrombin Time (Hemoclot), Dabigatran Plasma Levels, Endogenous thrombin generation, pre- and Post coagulation factor II / VII / IX / X
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02463591
|Contact: Alexander C Stehouwer, MDemail@example.com|
|Contact: Hilde Hop, MDfirstname.lastname@example.org|
|Principal Investigator:||Pieter Willem Kamphuisen, Prof. Dr.||University Medical Center Groningen|