A total of 27 subjects were enrolled and received HB including 3 lead-in subjects and were considered the safety analysis population (9 abdominal and 18 orthopedic). Twenty-four subjects were included in the efficacy analysis population (8 abdominal and 16 orthopedic). All subjects completed the study as planned.
The average age for all subjects was 62.8 years, with 51.9% male and 48.1% female. Regarding ethnicity: 22.2% of the subjects were Hispanic; 77.8% of the subjects were Caucasian; and 22.2% were African American (Table 1).
Table 1 – Subject Demographic Data by Surgery Type (Safety Analysis Population)
Measure
|
All
|
Abdominal
|
Orthopedic
|
Age
|
62.8 ± 8.64 (27) 63.0 [55.0, 68.0]
|
60.4 ± 10.70 (9) 55.0 [53.0, 66.0]
|
64.0 ± 7.48 (18) 64.5 [62.0, 68.0]
|
Gender
|
|
|
|
Male
|
14/27 (51.9%)
|
6/9 (66.7%)
|
8/18 (44.4%)
|
Female
|
13/27 (48.1%)
|
3/9 (33.3%)
|
10/18 (55.6%)
|
Ethnicity
|
|
|
|
Hispanic or Latino
|
6/27 (22.2%)
|
6/9 (66.7%)
|
0/18 (0.0%)
|
Not Hispanic or Latino
|
21/27 (77.8%)
|
3/9 (33.3%)
|
18/18 (100.0%)
|
Race
|
|
|
|
Caucasian
|
21/27 (77.8%)
|
9/9 (100.0%)
|
12/18 (66.7%)
|
African American
|
6/27 (22.2%)
|
0/9 (0.0%)
|
6/18 (33.3%)
|
American Indian or Alaska Native
|
0/27 (0.0%)
|
0/9 (0.0%)
|
0/18 (0.0%)
|
Asian
|
0/27 (0.0%)
|
0/9 (0.0%)
|
0/18 (0.0%)
|
Native Hawaiian or other Pacific Islander
|
0/27 (0.0%)
|
0/9 (0.0%)
|
0/18 (0.0%)
|
Other
|
0/27 (0.0%)
|
0/9 (0.0%)
|
0/18 (0.0%)
|
The surgical procedures consisted primarily of liver resections and total knee replacements, with the most common indications being metastatic cancers to the liver and osteoarthritis. The TBSs consisted of soft tissue, muscle, parenchyma, and bone. The average dimensions of the TBS were 21.1 ± 75.9 cm2, with larger dimensions in the abdominal arm (51.0 ± 131.0 cm2) and smaller dimensions in the orthopedic arm (6.1 ± 3.8 cm2).
For the primary endpoint, the mean paired Kappa statistic for the assignment of SG scores by 2 Investigators, the pairwise weighted Kappa statistics were 0.7441, 0.7640, and 0.8182 for each Investigator pair; the mean paired Kappa statistic was 0.7754 (Table 2).
Table 2 – Mean paired Kappa statistic for assignment of SPOT GRADE scores
Surgical Investigator Pair
|
Pairwise Weighted Kappa
|
Investigator Pair 1
|
0.7441
|
Investigator Pair 2
|
0.7640
|
Investigator Pair 3
|
0.8182
|
Mean
|
0.7754
|
The inter-rater agreement was also assessed for determining eligibility (SG score of 1, 2, or 3 [eligible] vs SG score of 0, 4, or 5 [ineligible]) and determining hemostasis (SG score of 0 vs SG score > 0). The mean paired Kappa for determining eligibility and hemostasis were both 0.9301. The pairwise simple Kappa statistics for the investigator pairs along with the mean paired Kappa are provided (Table 3).
Table 3 – Mean paired Kappa statistic for determining eligibility and hemostasis
Surgical Investigator Pair
|
Eligibility - Pairwise Simple Kappa
|
Hemostasis – Pairwise Simple Kappa
|
Investigator Pair 1
|
1.0000
|
1.0000
|
Investigator Pair 2
|
0.8902
|
0.8902
|
Investigator Pair 3
|
0.9000
|
0.9000
|
Mean
|
0.9301
|
0.9301
|
Change in gauze weight by SG score was examined. There was no statistically significant correlation between a change in gauze weight and SG scores.
Efficacy of HB was a secondary endpoint of this study. Rates of hemostasis across all study arms at 3, 6, and 10 minutes after HB application were 50.0%, 79.2%, and 91.7%, respectively (Table 4). Rates of hemostasis for the abdominal arm of the study at these time points were 25.0%, 50.0%, and 75.0% (Table 4). Rates of hemostasis for the orthopedic arm of the study at 3, 6, and 10 minutes after HB application were 62.5%, 93.8%, and 100.0%, respectively (Table 4).
Table 4 – Proportion of subjects achieving hemostasis at 3, 6, and 10 minutes
Time
|
All
|
Abdominal
|
Orthopedic
|
3 minutes
|
12/24 50.0% (31.4%, 68.6%)
|
2/8
25.0% (7.1%, 59.1%)
|
10/16 62.5% (38.6%, 81.5%)
|
6 minutes
|
19/24 79.2% (59.5%, 90.8%)
|
4/8
50.0% (21.5%, 78.5%)
|
15/16 93.8% (71.7%, 98.9%)
|
10 minutes
|
22/24 91.7% (74.2%, 97.7%)
|
6/8
75.0% (40.9%, 92.9%)
|
16/16 100.0% (80.6%, 100.0%)
|
Numbers are n/N percent (95% CI).
Wilson confidence limits (score based) are used in the table.
Cumulative numbers of subjects achieving hemostasis at each time are counted.
The median hospital stay was 4 days; no subjects were noted to have any clinical signs or symptoms of post-operative bleeding and there were no re-operations for bleeding. A total of 10 subjects (37.0%) experienced post-operative complications or adverse events (AEs). Forty-one AEs were reported, with 8 deemed as severe adverse events (SAEs). The IDMC reviewed and adjudicated each SAE and identified one as a possible severe adverse device event (SADE) – the development of non-occlusive thrombi in the portal and superior mesenteric veins. This study subject underwent a liver resection for metastatic rectal cancer. Prior to initiation of the hepatic transection, the portal pedicle was clamped (Pringle maneuver) for 30 minutes without heparinization. HB was applied to segment 2 liver parenchyma. The subject presented with development of thrombi 6 days postoperatively, which resolved with heparin administration. Right hepatectomy, cancer, and longer duration of Pringle maneuver are shown to be independent significant risk factors for portal vein thrombosis.[,,] All other SAEs were determined by study Investigators to be unrelated to HB.
All pre-defined conditions of study success were met (Table 5).
Table 5 – Conditions of study success
Parameter
|
Threshold for Success
|
Study Results
|
Meets Threshold
|
Mean paired Kappa statistic
|
> 0.61
|
0.7754
|
Yes
|
Mean paired Kappa statistic for determining eligibility
|
> 0.80
|
0.9301
|
Yes
|
Mean paired Kappa statistic for determining hemostasis
|
> 0.80
|
0.9301
|
Yes
|
No more than one UADE or SADE as determined by the IDMC
|
< 1 UADE or SADE
|
1 possible SADE
|
Yes
|