First clinical application of an actively reversible direct factor IXa inhibitor as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.
BACKGROUND
The ideal anticoagulant should prevent ischemic complications without increasing the risk of bleeding. Controlled anticoagulation is possible with the REG1 system, an RNA aptamer pair comprising the direct factor IXa inhibitor RB006 and its active control agent RB007.


RESULTS
This phase 2a study included a roll-in group (n=2) treated with REG1 plus glycoprotein IIb/IIIa inhibitors followed by 2 groups randomized 5:1 to REG1 or unfractionated heparin. In group 1 (n=12), RB006 was partially reversed with RB007 after percutaneous coronary intervention and fully reversed 4 hours later. In group 2 (n=12), RB006 was fully reversed with RB007 immediately after percutaneous coronary intervention. Femoral sheaths were removed after complete reversal. Patients were pretreated with aspirin and clopidogrel. End points included major bleeding within 48 hours; composite of death, myocardial infarction, or urgent target vessel revascularization within 14 days; and pharmacodynamic measures. All cases were successful, with final Thrombolysis in Myocardial Infarction grade 3 flow and no angiographic thrombotic complications. There were 2 ischemic end points in the REG1 group and 1 in the unfractionated heparin group, with 1 major bleed in the unfractionated heparin group. Median activated clotting time values rose from 151 to 236 seconds after RB006. Administration of the partial RB007 dose reversed anticoagulation to an intermediate activated clotting time value of 186 seconds. Complete reversal with RB007 returned the median activated clotting time value to 144 seconds. Both reversal strategies enabled scheduled femoral sheath removal.


CONCLUSIONS
This study demonstrates the clinical translation of a novel platform of anticoagulation targeting factor IXa and its active reversal to percutaneous coronary intervention and provides the basis for further investigation.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715455.
Cohen
Mauricio G
MG
Cardiovascular Division, University of Miami Miller School of Medicine, Miami, FL 33136, USA. mgcohen@med.miami.edu
Purdy
Drew A
DA
Rossi
Joseph S
JS
Grinfeld
Liliana R
LR
Myles
Shelley K
SK
Aberle
Laura H
LH
Greenbaum
Adam B
AB
Fry
Edward
E
Chan
Mark Y
MY
Tonkens
Ross M
RM
Zelenkofske
Steven
S
Alexander
John H
JH
Harrington
Robert A
RA
Rusconi
Christopher P
CP
Becker
Richard C
RC
D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000379:methods; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D052157:Aptamers, Nucleotide / Q000009:adverse effects / Q000627:therapeutic use; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D015949:Factor IXa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006493:Heparin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009841:Oligonucleotides / Q000009:adverse effects / Q000627:therapeutic use
D000925:Anticoagulants; D052157:Aptamers, Nucleotide; D009841:Oligonucleotides; C515724:RB 006; C515725:RB 007; C078918:ITF 300; D006493:Heparin; D015949:Factor IXa