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

Hemostasis Clinical Trial

Official title:

A Prospective, Randomized, Double-blind, Phase II Study to Evaluate the Safety and Efficacy of Topical Thrombin (Human) Grifols as an Adjunct to Hemostasis During Vascular, Hepatic, Soft Tissue, and Spinal Open Surgeries

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02014402
• Other study ID #: IG1202 (IG1202-A, -B, -C, -D)
• Status: Completed
• Phase: Phase 2
• First received: December 12, 2013
• Last updated: April 14, 2016
• Start date: December 2013
• Est. completion date: November 2015

Study information

• Verified date: April 2016
• Source: Grifols Biologicals Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This purpose of this clinical trial is 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 open surgical procedures. Approximately 180 subjects will be treated with either Topical Thrombin (Human) Grifols (120 subjects) or Bovine Thrombin JMI® (60 subjects). Subjects will be evaluated for identification of a target bleeding site (TBS) in which control of bleeding by standard surgical techniques is ineffective or impractical and requires an additional treatment to stop the bleeding. The Investigator (surgeon) will rate the intensity of bleeding at the TBS. Topical Thrombin (Human) Grifols or Bovine Thrombin JMI will then be applied to the TBS and the amount of bleeding at the TBS will be examined.

Description:

This is 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) open surgical procedures. Approximately 180 subjects will be 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 will be evaluated for identification of a target bleeding site (TBS) in which control of bleeding by conventional surgical techniques (including suture, ligature and cautery) is ineffective or impractical and requires an adjunct treatment to achieve hemostasis. The Investigator will rate the intensity of bleeding at the TBS. Topical Thrombin (Human) Grifols or Bovine Thrombin JMI will be applied to the TBS and hemostasis will be assessed at various timepoints during a 5-minute observation period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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).

• Require 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 should be exposed (IG1202-D).

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

Exclusion Criteria:

• Requires 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.

• Receiving an organ transplant.

• Undergoing another concurrent major surgical intervention beyond the liver (applies to hepatic surgery [IG1202-B] only; concurrent interventions on the pancreas, gall bladder, bile duct, or intestines are allowed).

• Undergoing a re-operative procedure, which is defined as a second, or successive, surgical procedure on the same anatomic location.

• Undergoing other vascular procedures during the same surgical session (applies to vascular surgery [IG1202-A] only; stenting and/or endarterectomy of the same artery are allowed).

• Undergone a therapeutic surgical procedure within 30 days from screening (diagnostic procedures are allowed).

• Previously included in this trial (i.e. each subject can only be enrolled once in this study).

• TBS cannot be identified according to the investigator's judgment.

• TBS has a severe bleeding according to the Investigator's judgment.

• Occurrence of major intra-operative complications that require 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 (applies to hepatic surgery [IG1202-B] only).

• Radiofrequency precoagulation of the liver resection surface, except focal use of radiofrequency as primary haemostatic treatment (applies to hepatic surgery [IG1202-B] only).

• Intra-operative change in planned surgical procedure which results in subject no longer meeting preoperative inclusion and/or exclusion criteria.

• Application of any topical haemostatic material on the cut soft tissue surface prior to application of the study treatment (applies to soft tissue surgery [IG1202-C] only).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemostasis

Intervention

Biological:
• Human thrombin
Thrombin purified from human plasma reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges
• Bovine thrombin
Thrombin of bovine origin reconstituted as a 1000 IU/mL solution in blinded syringes and applied using Gelfoam® sponges

Locations

Country	Name	City	State
United States	905	Baltimore	Maryland
United States	803	Boulder	Colorado
United States	508	Chapel Hill	North Carolina
United States	604	Evanston	Illinois
United States	503	Ft. Worth	Texas
United States	507	Gainesville	Florida
United States	908	Hartford	Connecticut
United States	900	Houston	Texas
United States	902	Jackson	Mississippi
United States	501, 901	Jacksonville	Florida
United States	800	Las Vegas	Nevada
United States	804	Lexington	Kentucky
United States	602	Los Angeles	California
United States	600	New York	New York
United States	700, 801	Pasadena	California
United States	606	Poughkeepsie	New York
United States	605	Salt Lake City	Utah
United States	802	Spokane	Washington
United States	805	Tucson	Arizona
United States	601	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Grifols, S.A.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects achieving hemostasis at the TBS	Hemostasis at the TBS defined by 'Yes" or "No" response (by Investigator) without the occurrence of re-bleeding through the completion of surgical closure.	5 minutes following the start of treatment application	No
Primary	Treatment-emergent adverse events	Treatment-emergent adverse events defined as adverse events (including suspected adverse reactions) occurring after the start of treatment until 30 (+/- 4) days post-surgery.	Start of treatment application through post-operative Day 30	Yes