Trial Outcomes & Findings for Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) During Soft Tissue Open Surgeries (NCT NCT01731938)

NCT ID: NCT01731938

Last Updated: 2017-02-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

327 participants

Primary outcome timeframe

From start of treatment until 4 minutes after treatment start

Results posted on

2017-02-23

Participant Flow

Participant milestones

Participant milestones
Measure	Fibrin Sealant (FS) Grifols 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).	Surgicel® 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.
Preliminary Part I STARTED	51	52
Preliminary Part I COMPLETED	48	44
Preliminary Part I NOT COMPLETED	3	8
Primary Part II STARTED	116	108
Primary Part II COMPLETED	103	95
Primary Part II NOT COMPLETED	13	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Fibrin Sealant (FS) Grifols 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).	Surgicel® 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.
Preliminary Part I Withdrawal by Subject	2	2
Preliminary Part I Physician Decision	1	0
Preliminary Part I Lost to Follow-up	0	3
Preliminary Part I Missed Week 6 visit	0	3
Primary Part II Withdrawal by Subject	5	4
Primary Part II Lost to Follow-up	4	5
Primary Part II Death	2	1
Primary Part II Missed Week 6 visit	2	3

Baseline Characteristics

Safety and Efficacy of Fibrin Sealant Grifols (FS Grifols) During Soft Tissue Open Surgeries

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fibrin Sealant (FS) Grifols Part I n=51 Participants 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).	Surgicel® Part I n=52 Participants 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.	Fibrin Sealant (FS) Grifols Part II n=116 Participants 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).	Surgicel® Part II n=108 Participants 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.	Total n=327 Participants Total of all reporting groups
Age, Continuous	47.17 years STANDARD_DEVIATION 25.635 • n=5 Participants	45.39 years STANDARD_DEVIATION 25.024 • n=7 Participants	48.51 years STANDARD_DEVIATION 14.369 • n=5 Participants	46.72 years STANDARD_DEVIATION 14.330 • n=4 Participants	47.21 years STANDARD_DEVIATION 18.444 • n=21 Participants
Age, Customized <18 years	8 Participants n=5 Participants	9 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	18 Participants n=21 Participants
Age, Customized Between 18 and 64 years	27 Participants n=5 Participants	28 Participants n=7 Participants	98 Participants n=5 Participants	90 Participants n=4 Participants	243 Participants n=21 Participants
Age, Customized >=65 years	16 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	18 Participants n=4 Participants	66 Participants n=21 Participants
Gender Female	27 Participants n=5 Participants	28 Participants n=7 Participants	87 Participants n=5 Participants	86 Participants n=4 Participants	228 Participants n=21 Participants
Gender Male	24 Participants n=5 Participants	24 Participants n=7 Participants	29 Participants n=5 Participants	22 Participants n=4 Participants	99 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	5 Participants n=7 Participants	20 Participants n=5 Participants	12 Participants n=4 Participants	41 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants	47 Participants n=7 Participants	96 Participants n=5 Participants	96 Participants n=4 Participants	286 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	22 Participants n=5 Participants	25 Participants n=4 Participants	57 Participants n=21 Participants
Race/Ethnicity, Customized White	46 Participants n=5 Participants	46 Participants n=7 Participants	93 Participants n=5 Participants	81 Participants n=4 Participants	266 Participants n=21 Participants
Race/Ethnicity, Customized Not Specified	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Fibrin Sealant (FS) Grifols n=116 Participants 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).	Surgicel® n=108 Participants 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.
Percentage of Subjects Achieving Hemostasis Within 4 Minutes After Treatment Start	82.8 percentage of participants	77.8 percentage of participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Fibrin Sealant (FS) Grifols n=116 Participants 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).	Surgicel® n=108 Participants 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.
Time to Hemostasis (TTH)	3.6 minutes Standard Error 0.25	4.2 minutes Standard Error 0.29

SECONDARY outcome

Timeframe: From start of treatment to 2, 3, 5, 7, and 10 minutes after start of treatment

Outcome measures

Outcome measures
Measure	Fibrin Sealant (FS) Grifols n=116 Participants 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).	Surgicel® n=108 Participants 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.
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	43.5 percentage of subjects
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	81.5 percentage of subjects
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	60.2 percentage of subjects
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	78.7 percentage of subjects
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	83.3 percentage of subjects

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Fibrin Sealant (FS) Grifols n=116 Participants 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).	Surgicel® n=108 Participants 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.
Treatments Failures	17.2 percentage of subjects	22.2 percentage of subjects

Adverse Events

Fibrin Sealant (FS) Grifols

Serious events: 17 serious events

Other events: 149 other events

Deaths: 0 deaths

Surgicel®

Serious events: 18 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Fibrin Sealant (FS) Grifols n=169 participants at risk 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).	Surgicel® n=158 participants at risk 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.
Injury, poisoning and procedural complications Procedural pain	54.4% 92/169 • Number of events 95 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	54.4% 86/158 • Number of events 86 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Injury, poisoning and procedural complications Procedural nausea	14.2% 24/169 • Number of events 25 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	19.6% 31/158 • Number of events 31 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Gastrointestinal disorders Nausea	13.6% 23/169 • Number of events 27 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	11.4% 18/158 • Number of events 19 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Gastrointestinal disorders Constipation	11.2% 19/169 • Number of events 19 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	7.0% 11/158 • Number of events 11 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
General disorders Pyrexia	7.1% 12/169 • Number of events 12 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	9.5% 15/158 • Number of events 16 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Blood and lymphatic system disorders Anemia	7.1% 12/169 • Number of events 12 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	8.9% 14/158 • Number of events 15 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Vascular disorders Hypertension	7.7% 13/169 • Number of events 13 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	7.6% 12/158 • Number of events 12 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Gastrointestinal disorders Vomiting	7.1% 12/169 • Number of events 13 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	5.7% 9/158 • Number of events 10 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Vascular disorders Hypotension	6.5% 11/169 • Number of events 11 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	3.2% 5/158 • Number of events 5 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Skin and subcutaneous tissue disorders Pruritus	5.3% 9/169 • Number of events 9 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	6.3% 10/158 • Number of events 10 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Injury, poisoning and procedural complications Incision site pain	5.3% 9/169 • Number of events 9 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	4.4% 7/158 • Number of events 7 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.
Infections and infestations Cervicitis	5.3% 9/169 • Number of events 9 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.	3.8% 6/158 • Number of events 6 • 6 months Adverse event data is based on the number of subjects who received study drug (safety population) in Preliminary Part (I) and Primary Part (II) of the study; 169 subjects in the FS Grifols group and 158 subjects in the Surgicel group. Two subjects who were randomized to the Surgicel treatment group received FS Grifols in error and are included in the FS Grifols treatment group.

Additional Information

Henry Li, PhD, RAC

Grifols Therapeutics, Inc.

Phone: 1-919-316-6042

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Site may publish results from the study, after providing Sponsor at least thirty days' notice prior to submitting a manuscript or other materials related to the study to any outside party. At Sponsor's request, the site will remove any confidential information (other than study results), and incorporate all reasonable comments by Sponsor, or delay publication or presentation for a period of up to 120 days to allow Sponsor to protect its interests in any Sponsor's Inventions.
Publication restrictions are in place

Restriction type: OTHER