Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial.
BACKGROUND
Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy.


METHODS
Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities.


RESULTS
The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04).


CONCLUSIONS
Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.
Lodge
J Peter A
JP
St. James's University Hospital, Hospital Haute-Pierre, Strasbourg, France. peterlodge@aol.com
Jonas
Sven
S
Oussoultzoglou
Elie
E
Malagó
Massimo
M
Jayr
Christian
C
Cherqui
Daniel
D
Anthuber
Matthias
M
Mirza
Darius F
DF
Kuhlman
Luce
L
Bechstein
Wolf-Otto
WO
Díaz
Juan Carlos Meneu
JC
Tartiere
Jack
J
Eyraud
Daniel
D
Fridberg
Marianne
M
Erhardtsen
Elisabeth
E
Mimoz
Oliver
O
D000328:Adult; D000368:Aged; D016063:Blood Loss, Surgical / Q000517:prevention & control; D004311:Double-Blind Method; D015942:Factor VIIa / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006498:Hepatectomy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000601:surgery*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D011517:Prothrombin Time / Q000706:statistics & numerical data; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D020246:Venous Thrombosis / Q000209:etiology
D011994:Recombinant Proteins; D015942:Factor VIIa