• Highlights
• Contents
• Indications and Usage
• Dosage and Administration
• Dosage Forms and Strengths
• Contraindications

• Warnings and Precautions
• Adverse Reactions
• Drug Interactions
• Use in Specific Populations
• Description

• Clinical Pharmacology
• Nonclinical Toxicology
• Clinical Studies
• References
• How Supplied/
  Storage and Handling

14 CLINICAL STUDIES

14.1 Study Design and Objectives

RECOTHROM was evaluated in a Phase 3 study conducted in 411 patients undergoing surgery in 1 of 4 surgical settings:  spinal surgery, hepatic resection, peripheral arterial bypass surgery, and arteriovenous graft formation for hemodialysis access. The study was a multiple-site, randomized, double-blind, controlled evaluation of RECOTHROM compared to bovine thrombin, each at a nominal concentration of 1000 U/mL topically applied to bleeding sites with an absorbable gelatin sponge [1].
A heterogeneous surgical population was enrolled in the Phase 3 study with no comorbidity exclusions except for prior heparin-induced thrombocytopenia.  Patient ages ranged from 21 to 89 years, gender was 53% male and 47% female, and the distribution by race was 68% white,18% black or African American, and 14% other. The distribution of these characteristics was similar in both the RECOTHROM and bovine thrombin treatment groups.
The objectives of the study were to evaluate the comparative efficacy, safety, and immunogenicity of RECOTHROM and bovine thrombin in combination with an absorbable gelatin sponge as adjuncts to hemostasis in surgery.  Efficacy was evaluated by the incidence of hemostasis within 10 minutes.  Bleeding appropriate for evaluation was defined as mild to moderate bleeding, either on its own or remaining after brisk bleeding was controlled by standard surgical modalities.  Although multiple bleeding sites could be treated, only 1 bleeding site per patient was used to determine primary effectiveness (the proximal anastomosis for peripheral arterial bypass surgery and the arterial anastomosis for arteriovenous graft formation).

14.2 Clinical Study Results

The Phase 3 study included 411 patients undergoing spinal surgery (n=122, 30%), hepatic surgery (n=125, 30%), peripheral arterial bypass surgery (n=88, 21%), and arteriovenous graft formation (n=76, 18%).  Table 2 summarizes the incidence of hemostasis within 10 minutes for each treatment for the 401 efficacy evaluable patients.  Ten patients were not included in the primary efficacy evaluation because they were not treated at 1 of 4 primary bleeding site types.  Overall, the incidence of hemostasis within 10 minutes was 95.4% for patients in the RECOTHROM group and 95.1% for patients in the comparator group.  This represents a 0.3% (95% CI, -3.7 to 4.4%) difference in patients receiving RECOTHROM compared to those receiving bovine thrombin, demonstrating that the 2 treatments have comparable efficacy.

The percentage of patients achieving hemostasis at 1.5, 3, 6, and 10 minutes is listed in Table 3.