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CompletedNCT01662856Updated Apr 6, 2017Results posted

Safety and Efficacy Study of Fibrin Sealant Grifols as an Adjunct to Hemostasis During Peripheral Vascular Surgery

A Phase 3 interventional study of Fibrin Sealant Grifols and Manual Compression in Vascular Surgical Bleeding, sponsored by Instituto Grifols, S.A.. Completed at 38 sites in 4 countries. Per ClinicalTrials.gov, last updated 2017-04-06.

Sponsored by Instituto Grifols, S.A. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
225
Allocation
Randomized
Sex
All
01

Study summary

The purpose of this study is to demonstrate that the application of Fibrin Sealant Grifols provides a measurable benefit when compared to hemostasis achieved through conventional surgical technique (suture) and by standard hemostatic action, such as mechanical pressure through manual compression. This study has a Preliminary Part (I) in which all subjects are treated with Fibrin Sealant Grifols and a Primary Part (II) in which subjects are randomized in a 2:1 ratio to either Fibrin Sealant Grifols or manual compression.

02

Conditions studied

  • Vascular Surgical Bleeding

Keywords

  • Vascular Surgery
  • Fibrin Sealant
  • Polytetrafluoroethylene (PTFE) grafts
03

In context

Lead sponsor

Instituto Grifols, S.A. is the lead sponsor of 24 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Hemoglobin (Hgb) ≥ 8.0 g/dL at Baseline (within 24 hours prior to surgical procedure).
  • Require elective (non-emergency), primary, open (non-laparoscopic; non-endovascular) peripheral vascular surgery.
  • Require one of the following peripheral vascular procedures involving proximal end-to-side arterial anastomosis utilizing coated or uncoated Polytetrafluoroethylene grafts: a) Femoral-femoral bypass grafting, b) Femoral-popliteal bypass grafting, c) Femoral-distal bypass grafting, d) Ilio-iliac bypass grafting, e) Ilio-femoral bypass grafting, f) Ilio-popliteal bypass grafting, g) Aorto-iliac bypass grafting, h) Aorto-femoral bypass grafting, i)Axillo-femoral bypass grafting, and j) Upper extremity vascular access for hemodialysis.
  • A target bleeding site can be identified.
  • Target bleeding site has moderate arterial bleeding.

Exclusion criteria

Exclusion Criteria:

  • Undergoing a re-operative procedure.
  • Undergoing other vascular procedures during the same surgical session (stenting and/or endarterectomy of the same artery are allowed).
  • Have an infection in the anatomic surgical area.
  • Have a history of severe (e.g. anaphylactic) reactions to blood or to any blood-derived product.
  • Have previous known sensitivity to any Fibrin Sealant Grifols, heparin, or protamine component.
  • Females who are pregnant or nursing a child at Baseline (within 24 hours prior to surgical procedure).
  • Have undergone a therapeutic surgical procedure within 30 days from the screening visit.
  • Target bleeding site cannot be identified.
  • Target bleeding site has mild or severe arterial bleeding.
  • Occurrence of major intraoperative complications that require resuscitation or deviation from the planned surgical procedure.
  • Intraoperative change in planned surgical procedure, which results in subject no longer meeting preoperative inclusion and/or exclusion criteria.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Enrollment
225 participants (actual)

Study arms

  • Experimental
    Fibrin Sealant 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).

    Biological: Fibrin Sealant Grifols

  • Active comparator
    Manual Compression

    Direct manual compression of target bleeding site with gauze/laparotomy pads.

    Procedure: Manual Compression

Interventions

  • BiologicalFibrin Sealant Grifols

    Combination of 3 mL fibrinogen and 3 mL thrombin in separate syringes assembled on a syringe holder (6 mL of solution in total).

  • ProcedureManual Compression

    Direct manual compression of target bleeding site with gauze/laparotomy pads.

06

What researchers measure

Primary outcomes

  1. Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start

    Subjects achieving hemostasis at the target bleeding site by 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

Secondary outcomes

  1. Time to Hemostasis (TTH)

    Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start. In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated. All calculations were performed using SAS PROC LIFETEST

    Time frame: From start of treatment until 10 minutes after treatment start

  2. Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points

    Cumulative proportion of subjects having achieved hemostasis by each of the following time points: * At 5 minutes following start of study treatment * At 7 minutes following start of study treatment * At 10 minutes following start of study treatment

    Time frame: From start of treatment until 10 minutes after treatment start

  3. Prevalence of Treatment Failures

    Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.

    Time frame: From start of treatment until 10 minutes after treatment start

07

Results

Posted Apr 6, 2017

Participant flow

Part I + Part II (Overall Study)
Participant flow — Part I + Part II (Overall Study)
MilestoneFibrin Sealant GrifolsManual Compression
Started16857
Completed study up to week 616456
Completed15255
Not completed162
Primary Part II
Participant flow — Primary Part II
MilestoneFibrin Sealant GrifolsManual Compression
Started10957
Completed study up to week 610656
Completed9955
Not completed102

Outcome measures

PrimaryProportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start

Subjects achieving hemostasis at the target bleeding site by 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
Reported as:
Number · Percent of subjects achieving hemostasis
Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start
Percent of subjects achieving hemostasisFibrin Sealant GrifolsManual Compression
Proportion of Subjects Achieving Hemostasis by Four Minutes After Treatment Start76.122.8
SecondaryTime to Hemostasis (TTH)

Time in minutes for achievement of hemostasis at the target bleeding site measured from the start of treatment until 10 minutes after treatment start. In the Fibrin Sealant Grifols treatment group, the median TTH was calculated based on the estimated survival function S(t), and it is the smallest time at which S(t) is at or below 50%. The 95% CI for the median TTH, on the other hand, was calculated based on the CI for the survival function S(t). The 95% CI for the median TTH was the set of all time points for which the 95% CI of the survival function contains 0.5 (since median is the 50% percentile). Sometimes, the confidence limits for the median cannot be estimated. In our case, the hemostasis was assessed on a discrete scale, and it happened that for all the time points assessed none of the 95% CI of the survival function S(t) contained 0.5. As a result, neither the lower nor the upper limit could be estimated. All calculations were performed using SAS PROC LIFETEST

Time frame:
From start of treatment until 10 minutes after treatment start
Reported as:
Median · minutes
Time to Hemostasis (TTH)
minutesFibrin Sealant GrifolsManual Compression
Time to Hemostasis (TTH)4.0 (NA to NA)NA (10.00 to NA)
SecondaryCumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points

Cumulative proportion of subjects having achieved hemostasis by each of the following time points: * At 5 minutes following start of study treatment * At 7 minutes following start of study treatment * At 10 minutes following start of study treatment

Time frame:
From start of treatment until 10 minutes after treatment start
Reported as:
Number · Percent of subjects achieving hemostasis
Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points
Percent of subjects achieving hemostasisFibrin Sealant GrifolsManual Compression
Hemostasis by 5 minutes80.728.1
Hemostasis by 7 minutes84.435.1
Hemostasis by 10 minutes88.145.6
SecondaryPrevalence of Treatment Failures

Protocol-defined bleeding at the target bleeding site after the start of treatment or the use of alternative hemostatic treatments (with exception of reversal of heparin) or maneuvers at the target bleeding site after the start of treatment.

Time frame:
From start of treatment until 10 minutes after treatment start
Reported as:
Number · percent of subjects
Prevalence of Treatment Failures
percent of subjectsFibrin Sealant GrifolsManual Compression
Prevalence of Treatment Failures23.977.2

Adverse events

Collected over Adverse event data were collected from the time informed consent was obtained through the Post-Operative Week 6 (±4 days) Visit. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Fibrin Sealant Grifols—34/168 (20.2%)132/168 (78.6%)
Manual Compression—11/57 (19.3%)41/57 (71.9%)
Most frequent serious events
Showing 10 of 55
Most frequent serious events
EventFibrin Sealant GrifolsManual Compression
GangreneInfections and infestations1/1682/57
Vascular graft thrombosisInjury, poisoning and procedural complications1/1682/57
PneumoniaInfections and infestations3/1680/57
Postoperative wound infectionInfections and infestations3/1681/57
Acute coronary syndromeCardiac disorders0/1681/57
Myocardial infarctionCardiac disorders2/1681/57
Non-cardiac chest painGeneral disorders0/1681/57
PyrexiaGeneral disorders0/1681/57
Respiratory tract infectionInfections and infestations0/1681/57
SepsisInfections and infestations0/1681/57
Most frequent other events
Most frequent other events
EventFibrin Sealant GrifolsManual Compression
Procedural painInjury, poisoning and procedural complications58/16821/57
PyrexiaGeneral disorders19/1686/57
Oedema peripheralGeneral disorders13/1681/57
ConstipationGastrointestinal disorders7/1684/57
Body temperature increasedInvestigations10/1684/57
AnaemiaBlood and lymphatic system disorders10/1682/57
NauseaGastrointestinal disorders10/1682/57
Anaemia postoperativeInjury, poisoning and procedural complications9/1682/57
VomitingGastrointestinal disorders4/1683/57
HypotensionVascular disorders2/1683/57

Baseline characteristics

Age, Continuous
Age, Continuous(years)Fibrin Sealant GrifolsManual CompressionTotal
Mean63.65 ± 9.03662.04 ± 10.73463.24 ± 9.496
Age, Customized
Age, Customized(participants)Fibrin Sealant GrifolsManual CompressionTotal
Between 18 and 64 years9032122
>=65 years7825103
Sex: Female, Male
Sex: Female, Male(Participants)Fibrin Sealant GrifolsManual CompressionTotal
Female512677
Male11731148
Region of Enrollment
Region of Enrollment(participants)Fibrin Sealant GrifolsManual CompressionTotal
Russian Federation18321
Hungary492372
United States691685
Serbia321547
08

Study locations

38 sites
  • 407
    Florence, Alabama 35630, United States
  • 125
    Palo Alto, California 94304, United States
  • 119
    San Diego, California 92120, United States
  • 149
    Jacksonville, Florida 32207, United States
  • 148
    Jacksonville, Florida 32216, United States
  • 137
    Tampa, Florida 33606, United States
  • 140
    Atlanta, Georgia 30303, United States
  • 114
    Iowa City, Iowa 52242, United States
  • 110
    Lexington, Kentucky 40536, United States
  • 146
    Baton Rouge, Louisiana 70809, United States
  • 132
    New Orleans, Louisiana 70112, United States
  • 129
    Baltimore, Maryland 21201, United States
  • 135
    Bethesda, Maryland 20889, United States
  • 102
    Boston, Massachusetts 02118, United States
  • 142
    Bronx, New York 10467-2401, United States
  • 406
    Manhasset, New York 11030, United States
  • 113
    Stony Brook, New York 11794, United States
  • 409
    Dayton, Ohio 45409, United States
  • 104
    Toledo, Ohio 43606, United States
  • 100, 128
    Pittsburgh, Pennsylvania 15212, United States
  • 115
    West Reading, Pennsylvania 19611, United States
  • 147
    Fort Worth, Texas 76107, United States
  • 402
    Houston, Texas 77024, United States
  • 139
    Salt Lake City, Utah 84132-3201, United States
  • 103
    Seattle, Washington 98104, United States
  • 138
    Tacoma, Washington 98431, United States
  • 111
    Madison, Wisconsin 53792, United States
  • 501
    Miskolc, 03526, Hungary
  • 500
    Pecs, 07623, Hungary
  • 502
    Veszprém, 8200, Hungary
  • 540
    Novosibirsk, 630055, Russian Federation
  • 542
    Rostov-on-Don, 344022, Russian Federation
  • 541
    Saint-Petersburg, 194354, Russian Federation
  • 543
    Saint-Petersburg, 195271, Russian Federation
  • 544
    Saint-Petersburg, 197374, Russian Federation
  • 523
    Belgrade, 11000, Serbia
  • 521
    Belgrade, 11040, Serbia
  • 522,524
    Novi Sad, 21000, Serbia
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 6, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01662856
Lead sponsor
Instituto Grifols, S.A.
Responsible party
Sponsor
First posted
Aug 10, 2012
Start date
Aug 2012
Primary completion
Dec 2015
Completion
Dec 2015
Results posted
Apr 6, 2017
Last update
Apr 6, 2017
View the source record on ClinicalTrials.gov ↗

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