Evaluation of the topical hemostatic efficacy and safety of TISSEEL VH S/D fibrin sealant compared with currently licensed TISSEEL VH in patients undergoing cardiac surgery: a phase 3, randomized, double-blind clinical study.
OBJECTIVE
TISSEEL VH is the only commercially available fibrin sealant indicated as an adjunct to conventional methods of hemostasis during cardiac surgery. A next generation fibrin sealant (TISSEEL VH S/D) has been developed in frozen, ready-to-use form with an added virus inactivation step (solvent/detergent [S/D] treatment) to provide added safety and convenience to the currently licensed product. This study was performed to compare efficacy and safety of the two products.


METHODS
Phase 3, prospective, randomized, double-blind, multicenter study to compare TISSEEL VH S/D to TISSEEL VH during cardiac surgery. The primary efficacy endpoint was the proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure.


RESULTS
The proportion of patients who achieved hemostasis at the primary treatment site within 5 min, and maintained hemostasis until surgical closure was 88.2% for TISSEEL VH S/D and 89.6% for TISSEEL VH in the intent-to-treat population. The difference in proportions, TISSEEL VH S/D minus TISSEEL VH, was 1.4% with a standard error of 3.70%. The lower 97.5% confidence bound of this difference was 8.6%, which is above the predefined noninferiority margin of 15%. Therefore, TISSEEL VH S/D is at least as efficacious as TISSEEL VH. The safety profile of TISSEEL VH S/D was very similar to that of currently licensed TISSEEL VH as assessed by the safety endpoints.


CONCLUSIONS
TISSEEL VH S/D is safe and effective for use as an adjunct to hemostasis in patients undergoing cardiac surgery.
Lowe
J
J
Duke University Medical Center, Durham, NC, USA.
Luber
J
J
Levitsky
S
S
Hantak
E
E
Montgomery
J
J
Schiestl
N
N
Schofield
N
N
Marra
S
S
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004311:Double-Blind Method; D005260:Female; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006488:Hemostasis, Surgical / Q000379:methods*; D006490:Hemostatics / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019106:Postoperative Hemorrhage / Q000517:prevention & control*; D011446:Prospective Studies; D013249:Sternum / Q000601:surgery; D013997:Time Factors; D014014:Tissue Adhesives / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
D015718:Fibrin Tissue Adhesive; D006490:Hemostatics; D014014:Tissue Adhesives