Soft Tissue Surgical Bleeding
Conditions
Keywords
Fibrin Sealant, Soft tissue open surgery, Oxidized cellulose pads
Brief summary
This study is designed to assess the safety and efficacy of fibrin sealant (FS) Grifols in patients undergoing elective (non-emergency) soft tissue open surgery where bleeding may be present. The purpose of this study is to demonstrate that FS Grifols is not inferior to commercially-available oxidized cellulose pads (Surgicel®) in providing benefit in the time to hemostasis (i.e, the stoppage of bleeding). This study has a Preliminary Part (I) for study teams to become familiar with the application of FS Grifols and a Primary Part (II) to assess the safety and efficacy of FS Grifols. In both parts of the study, patients will be randomized in a 1:1 ratio to either FS Grifols or Surgicel.
Interventions
BIOLOGICALFibrin Sealant (FS) Grifols
Fibrin Sealant (FS) Grifols: The maximum total volume of FS Grifols allowed to be applied at the target bleeding site by dripping or spraying was approximately 12 mL (equivalent to the full content of 2 FS Grifols kits).
DEVICESurgicel®
Up to four Surgicel® sheets applied to the target bleeding site according to Package Insert instructions and the surgeon's usual clinical practice.
Sponsors
Instituto Grifols, S.A.
Grifols Biologicals, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline (within 24 hours prior to surgical procedure). * Require elective (non-emergency), open (non-laparoscopic) surgical procedure involving soft (non-parenchymous) tissue. * Target bleeding site is identified on soft tissue during urologic, gynecologic or general surgery procedures: 1) Simple or radical nephrectomies, 2) Total adrenalectomies, 3) Radical prostatectomies, 4) Pyeloplasties, 5) Radical cystectomies, 6) Simple or radical hysterectomies, 7) Lymphadenectomies (in the retroperitoneal or pelvic region only), 8) Retroperitoneal tumor resections, 9) Mastopexies, and 10) Abdominoplasties. * A target bleeding site can be identified. * Target bleeding site has moderate bleeding according to the Investigator's judgment.
Exclusion criteria
* Require thoracic, abdominal, retroperitoneal or pelvic surgery due to trauma. * Infection in the anatomic surgical area. * History of severe (e.g. anaphylactic) reactions to blood or to any blood-derived product. * Previous known sensitivity to any FS Grifols component or any Surgicel® component. * Females who are pregnant or nursing a child at Baseline (within 24 hours prior to surgical procedure). * Receiving an organ transplant during the same surgical procedure. * Undergone a therapeutic surgical procedure within 30 days from the screening visit. * A target bleeding site cannot be identified. * The target bleeding site has a mild or severe bleeding. * Occurrence of major intraoperative complications that require resuscitation or deviation from the planned surgical procedure. * Application of any topical haemostatic material on the cut soft tissue surface identified as the target bleeding site prior to application of the study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving Hemostasis Within 4 Minutes After Treatment Start | From start of treatment until 4 minutes after treatment start | Subjects achieving hemostasis at the target bleeding site within 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | From start of treatment to 2, 3, 5, 7, and 10 minutes after start of treatment | — |
| Time to Hemostasis (TTH) | From start of treatment to the end of the 10-minute observational period | TTH was measured from the start of treatment to the achievement of hemostasis at the target bleeding site, or to the end of the 10-minute observational period when hemostasis had not yet been achieved. |
| Treatments Failures | From start of treatment to time of completion of surgical closure. | The following were considered treatment failures: Persistent bleeding at the TBS beyond T4, Breakthrough (brisk and forceful) bleeding from the TBS that jeopardized subject safety according to the investigator's judgment at any moment during the 10 minute observational period and until TClosure, Re-bleeding at the TBS after the assessment of the primary efficacy endpoint at T4 and until TClosure Use of alternative hemostatic treatments or maneuvers (other than the study treatment) at the TBS during the 10-minute observational period and until TClosure or use of study treatment at the TBS beyond T4 and until TClosure. |
Countries
Hungary, Serbia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fibrin Sealant (FS) Grifols Part I Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).
Fibrin Sealant (FS) Grifols: The maximum total volume of FS Grifols allowed to be applied at the target bleeding site by dripping or spraying was approximately 12 mL (equivalent to the full content of 2 FS Grifols kits). | 51 |
| Surgicel® Part I Surgicel® is a sterile, absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.
Surgicel®: Up to four Surgicel® sheets applied to the target bleeding site according to Package Insert instructions and the surgeon's usual clinical practice. | 52 |
| Fibrin Sealant (FS) Grifols Part II Fibrin Sealant Grifols consisting of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).
Fibrin Sealant (FS) Grifols: The maximum total volume of FS Grifols allowed to be applied at the target bleeding site by dripping or spraying was approximately 12 mL (equivalent to the full content of 2 FS Grifols kits). | 116 |
| Surgicel® Part II Surgicel® is a sterile, absorbable knitted fabric prepared by the controlled oxidation of regenerated cellulose.
Surgicel®: Up to four Surgicel® sheets applied to the target bleeding site according to Package Insert instructions and the surgeon's usual clinical practice. | 108 |
| Total | 327 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Preliminary Part I | Lost to Follow-up | 0 | 3 |
| Preliminary Part I | Missed Week 6 visit | 0 | 3 |
| Preliminary Part I | Physician Decision | 1 | 0 |
| Preliminary Part I | Withdrawal by Subject | 2 | 2 |
| Primary Part II | Death | 2 | 1 |
| Primary Part II | Lost to Follow-up | 4 | 5 |
| Primary Part II | Missed Week 6 visit | 2 | 3 |
| Primary Part II | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Fibrin Sealant (FS) Grifols Part I | Surgicel® Part I | Fibrin Sealant (FS) Grifols Part II | Surgicel® Part II | Total |
|---|---|---|---|---|---|
| Age, Continuous | 47.17 years STANDARD_DEVIATION 25.635 | 45.39 years STANDARD_DEVIATION 25.024 | 48.51 years STANDARD_DEVIATION 14.369 | 46.72 years STANDARD_DEVIATION 14.33 | 47.21 years STANDARD_DEVIATION 18.444 |
| Age, Customized <18 years | 8 Participants | 9 Participants | 1 Participants | 0 Participants | 18 Participants |
| Age, Customized >=65 years | 16 Participants | 15 Participants | 17 Participants | 18 Participants | 66 Participants |
| Age, Customized Between 18 and 64 years | 27 Participants | 28 Participants | 98 Participants | 90 Participants | 243 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 20 Participants | 12 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 47 Participants | 96 Participants | 96 Participants | 286 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Gender Female | 27 Participants | 28 Participants | 87 Participants | 86 Participants | 228 Participants |
| Gender Male | 24 Participants | 24 Participants | 29 Participants | 22 Participants | 99 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 5 Participants | 22 Participants | 25 Participants | 57 Participants |
| Race/Ethnicity, Customized Not Specified | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 46 Participants | 46 Participants | 93 Participants | 81 Participants | 266 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 149 / 169 | 139 / 158 |
| serious Total, serious adverse events | 17 / 169 | 18 / 158 |
Outcome results
Primary
Percentage of Subjects Achieving Hemostasis Within 4 Minutes After Treatment Start
Subjects achieving hemostasis at the target bleeding site within 4 minutes following the start of treatment without the occurrence of re-bleeding until the completion of surgical closure.
Time frame: From start of treatment until 4 minutes after treatment start
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrin Sealant (FS) Grifols | Percentage of Subjects Achieving Hemostasis Within 4 Minutes After Treatment Start | 82.8 percentage of participants |
| Surgicel® | Percentage of Subjects Achieving Hemostasis Within 4 Minutes After Treatment Start | 77.8 percentage of participants |
Secondary
Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart.
Time frame: From start of treatment to 2, 3, 5, 7, and 10 minutes after start of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fibrin Sealant (FS) Grifols | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T3 | 75.9 percentage of subjects |
| Fibrin Sealant (FS) Grifols | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T7 | 86.2 percentage of subjects |
| Fibrin Sealant (FS) Grifols | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T2 | 53.4 percentage of subjects |
| Fibrin Sealant (FS) Grifols | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T10 | 89.7 percentage of subjects |
| Fibrin Sealant (FS) Grifols | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T5 | 83.6 percentage of subjects |
| Surgicel® | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T10 | 83.3 percentage of subjects |
| Surgicel® | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T3 | 60.2 percentage of subjects |
| Surgicel® | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T5 | 78.7 percentage of subjects |
| Surgicel® | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T7 | 81.5 percentage of subjects |
| Surgicel® | Cumulative Proportion of Subjects Achieving Hemostasis at the Target Bleeding Site by 2 (T2), 3 (T3), 5 (T5), 7 (T7), and 10 (T10) Minutes After TStart. | Hemostasis by T2 | 43.5 percentage of subjects |
Secondary
Time to Hemostasis (TTH)
TTH was measured from the start of treatment to the achievement of hemostasis at the target bleeding site, or to the end of the 10-minute observational period when hemostasis had not yet been achieved.
Time frame: From start of treatment to the end of the 10-minute observational period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Fibrin Sealant (FS) Grifols | Time to Hemostasis (TTH) | 3.6 minutes | Standard Error 0.25 |
| Surgicel® | Time to Hemostasis (TTH) | 4.2 minutes | Standard Error 0.29 |
Secondary
Treatments Failures
The following were considered treatment failures: Persistent bleeding at the TBS beyond T4, Breakthrough (brisk and forceful) bleeding from the TBS that jeopardized subject safety according to the investigator's judgment at any moment during the 10 minute observational period and until TClosure, Re-bleeding at the TBS after the assessment of the primary efficacy endpoint at T4 and until TClosure Use of alternative hemostatic treatments or maneuvers (other than the study treatment) at the TBS during the 10-minute observational period and until TClosure or use of study treatment at the TBS beyond T4 and until TClosure.
Time frame: From start of treatment to time of completion of surgical closure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fibrin Sealant (FS) Grifols | Treatments Failures | 17.2 percentage of subjects |
| Surgicel® | Treatments Failures | 22.2 percentage of subjects |