Safety and Efficacy of Topical Thrombin (Human) Grifols as an Adjunct to Hemostasis During Surgery

NCT ID: NCT02014402

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2015-11-30

Brief Summary

This purpose of this clinical trial was to study the safety and efficacy of Topical Thrombin (Human) Grifols as an add-on treatment to help stop bleeding during vascular, liver, soft tissue, and spinal surgical procedures.

Detailed Description

This was a prospective, randomized, double-blind, controlled, Phase II study to evaluate the safety and efficacy of Topical Thrombin (Human) Grifols as an adjunct to hemostasis during vascular (IG1202-A), hepatic (IG1202-B), soft tissue (IG1202-C), and spinal (IG1202-D) surgical procedures. Approximately 180 subjects were randomized into 1 of 2 treatment groups in a 2:1 ratio: Topical Thrombin (Human) Grifols (120 subjects) or Bovine Thrombin JMI (60 subjects) among the 4 types of surgeries. Randomized subjects were evaluated for identification of a target bleeding site (TBS) in which control of bleeding by conventional surgical techniques (including suture, ligature and cautery) was ineffective or impractical and required an adjunct treatment to achieve hemostasis. The Investigator rated the intensity of bleeding at the TBS. Topical Thrombin (Human) Grifols or Bovine Thrombin JMI was applied to the TBS and the time to hemostasis was assessed at various timepoints during a 5-minute observation period.

Subjects were evaluated by surgery type and by integrated analysis of clinical studies IG1202-A, IG1202-B, IG1202-C, and IG1202-D.

Conditions

Hemostasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

IG1202-A (Vascular)

Group Type: EXPERIMENTAL

Human thrombin

Intervention Type: BIOLOGICAL

Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Bovine thrombin

Intervention Type: BIOLOGICAL

Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

IG1202-B (Hepatic)

Group Type: EXPERIMENTAL

Human thrombin

Intervention Type: BIOLOGICAL

Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Bovine thrombin

Intervention Type: BIOLOGICAL

Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

IG1202-C (Soft Tissue)

Group Type: EXPERIMENTAL

Human thrombin

Intervention Type: BIOLOGICAL

Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Bovine thrombin

Intervention Type: BIOLOGICAL

Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

IG1202-D (Spinal)

Group Type: EXPERIMENTAL

Human thrombin

Intervention Type: BIOLOGICAL

Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Bovine thrombin

Intervention Type: BIOLOGICAL

Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Interventions

Human thrombin

Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Intervention Type: BIOLOGICAL

Bovine thrombin

Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Pre-operative (at Baseline Assessments Visit) hemoglobin (Hgb) ≥9.0 g/dL (deciliter)
• Pre-operative (at Baseline Assessments Visit) fibrinogen level ≥150 mg/dL (functional method).
• Required one of the following procedures:

1. An elective (non-emergency), open (non-laparoscopic; non- endovascular) surgical procedure involving a native artery-graft end-to-side proximal anastomosis utilizing coated or uncoated polytetrafluoroethylene (PTFE) graft (IG1202-A).

2. An elective (non-emergency), open (non-laparoscopic) hepatic resection (anatomic and non-anatomic resections of at least one anatomical hepatic segment or equivalent tissue volume) (IG-1202-B).

3. An elective (non-emergency), open (non-laparoscopic), surgical procedure involving soft (non-parenchymous) tissue (IG1202-C).

4. An elective (non-emergency), spinal surgical procedure in which the epidural venous plexus was exposed (IG1202-D).

• A target bleeding site (TBS) was identified according to the Investigator's judgment, and the TBS had mild or moderate bleeding according to the Investigator's judgment.

Exclusion Criteria

• Required surgical procedure due to trauma (except for spinal surgery).
• Infection in the anatomic surgical area.
• History of severe (e.g. anaphylactic) reactions to blood or to any blood-derived (human or animal) product.
• Previous known sensitivity to any Topical Thrombin (Human) Grifols component, any Bovine Thrombin JMI component, porcine collagen, and heparin or protamine (vascular surgery only) component.
• Received an organ transplant.
• Underwent another concurrent major surgical intervention beyond the liver (applied to hepatic surgery [IG1202-B] only; concurrent interventions on the pancreas, gall bladder, bile duct, or intestines were allowed).
• Underwent a re-operative procedure, which was defined as a second, or successive, surgical procedure on the same anatomic location.
• Underwent other vascular procedures during the same surgical session (applied to vascular surgery [IG1202-A] only; stenting and/or endarterectomy of the same artery were allowed).
• Underwent a therapeutic surgical procedure within 30 days from screening (diagnostic procedures were allowed).
• Previously included in this trial (i.e. each subject could only be enrolled once in this study).
• TBS could not be identified according to the investigator's judgment.
• TBS had a severe bleeding according to the Investigator's judgment.
• Occurrence of major intra-operative complications that required resuscitation or deviation from the planned surgical procedure.
• Application of any topical haemostatic material on the resection surface of the liver prior to application of the study treatment (applied to hepatic surgery [IG1202-B] only).
• Radiofrequency precoagulation of the liver resection surface, except focal use of radiofrequency as primary haemostatic treatment (applied to hepatic surgery [IG1202-B] only).
• Application of any topical haemostatic material on the cut soft tissue surface prior to application of the study treatment (applied to soft tissue surgery [IG1202-C] only).

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Grifols, S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

805

Tucson, Arizona, United States

602

Los Angeles, California, United States

700, 801

Pasadena, California, United States

803

Boulder, Colorado, United States

908

Hartford, Connecticut, United States

601

Washington D.C., District of Columbia, United States

507

Gainesville, Florida, United States

501, 901

Jacksonville, Florida, United States

604

Evanston, Illinois, United States

804

Lexington, Kentucky, United States

905

Baltimore, Maryland, United States

902

Jackson, Mississippi, United States

800

Las Vegas, Nevada, United States

600

New York, New York, United States

606

Poughkeepsie, New York, United States

508

Chapel Hill, North Carolina, United States

503

Fort Worth, Texas, United States

900

Houston, Texas, United States

605

Salt Lake City, Utah, United States

802

Spokane, Washington, United States

Countries

United States

References

Minkowitz H, Navarro-Puerto J, Lakshman S, Singla S, Cousar C, Kim R, Villavicencio A, Kirksey L, Ayguasanosa J; Clinical Investigation Study Group on Topical Thrombin (Human) Grifols in Surgery. Prospective, Randomized, Phase II, Non-Inferiority Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as Adjunct to Hemostasis During Vascular, Hepatic, Soft Tissue, and Spinal Open Surgery. J Am Coll Surg. 2019 Nov;229(5):497-507.e1. doi: 10.1016/j.jamcollsurg.2019.07.008. Epub 2019 Jul 31.

Reference Type: DERIVED

PMID: 31376435 (View on PubMed)

Other Identifiers

IG1202 (IG1202-A, -B, -C, -D)

Identifier Type: -

Identifier Source: org_study_id