No registrations found.
ID
Source
Brief title
Health condition
Healthy male subjects between 18 and 50 year who have no medical history of thrombotic disease or bleeding disorders will be included in the study. They must have a normal physical examination and laboratory screen tests. They will not use any medication at least 14 days before the study days.
Sponsors and support
Academic Medical Center
Meibergdreef 9
Amsterdam
s.middeldorp@amc.uva.nl
Intervention
Outcome measures
Primary outcome
The primary outcome is the reversal (normalisation) of coagulation assays, at the end of oral f-Xa inhibitor administration and after the infusion of PCC or placebo.
Secondary outcome
N/A
Background summary
Rivaroxaban and apixaban lack a specific reversal agent. Fifty units/kg of 4-factor prothrombin complex concentrate (PCC, Cofact®) completely reversed the anticoagulant effect of rivaroxaban in healthy subjects. We hypothesized that infusion with doses of 37.5 or 25 units/kg of PCC would be able to reverse the anticoagulant effect of rivaroxaban and apixaban, both factor Xa inhibitors. In a randomized, double blind, placebo-controlled study, 12 healthy volunteers taking rivaroxaban 15 mg or apixaban 10 mg twice daily, received either a single bolus of PCC 37.5 units/kg, PCC 25 units/kg or placebo, with a wash-out period of 18 days in between infusions. The primary outcome was the effect of PCC on measures of thrombin generation, e.g. endogenous thrombin potential (ETP), after PCC or placebo infusion.
Study objective
Reversibility of oral direct factor Xa inhibitors rivaroxaban and apixaban will be the same when a lower dosage of prothrombin complex concentrate (Cofact®) is used. Infusion with doses of 37.5 or 25 units/kg of PCC would be able to reverse the anticoagulant effect of rivaroxaban and apixaban.
Study design
Day -7: Randomization for PCC or saline,
baseline coagulation tests;
Days -7 to 0:
1. Group 1: Apixaban orally, 10 mg twice daily, for 7 and a half days (15 doses);
2. Group 2: Rivaroxaban orally, 15 mg twice daily, for 7 and a half days (15 doses).
Day 0: PCC/saline administration, scheduled coagulation tests;
Day 1: Scheduled coagulation tests.
Intervention
Intravenous administration of PCC (Cofact) 25 IU/kg or PCC (Cofact) 37.5 IU/kg or placebo (saline).
P.O. Box 22660
S. Middeldorp
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5665976
alife@amc.uva.nl
P.O. Box 22660
S. Middeldorp
Meibergdreef 9
Amsterdam 1100 DD
The Netherlands
+31 (0)20 5665976
alife@amc.uva.nl
Inclusion criteria
1. Healthy male subjects as documented by laboratory screen tests (including HIV/HBV/HCV screening), personal medical history and normal physical examination;
2. Age ≥18 years, < 50 years;
3. No personal history of thrombotic disease/bleeding disorders;
4. No significant family history of thrombotic disease/bleeding disorders, such as recurrent thrombotic/bleeding events or thrombotic/bleeding events in the absence of any risk factors;
5. Able to provide written informed consent.
Exclusion criteria
1. History of allergic reaction to blood products;
2. Current participation in any other investigational drug study or within the past 30 days;
3. Presence of any condition that, as judged by the investigator, would place the subject at increased risk of harm if he participated in the study.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL3388 |
| NTR-old | NTR3559 |
| Other | : |
| ISRCTN | ISRCTN wordt niet meer aangevraagd. |
Summary results
Elise S. Eerenberg, MD; Pieter W. Kamphuisen, MD; Meertien K. Sijpkens, BSc; Joost C. Meijers, PhD; Harry R. Buller, MD; Marcel Levi, MD