Clinical trial NCT02014402: Safety and Efficacy of Topical Thrombin (Human) Grifols as an Adjunct to Hemostasis During Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemostasis
Keywords: Vascular surgery
Hepatic surgery
Soft tissue surgery
Spinal surgery
Lead sponsor: Grifols Biologicals, LLC
Sponsor class: INDUSTRY
First posted: 2013-12-18
Enrollment: 181
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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).
* Intra-operative change in planned surgical procedure which resulted 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 (applied to soft tissue surgery \[IG1202-C\] only).

Primary outcomes:
measure: Proportion of Subjects Achieving Hemostasis by Five Minutes After Treatment Start at the TBS
timeFrame: From start of treatment until 5 minutes after treatment start
Secondary outcomes:
measure: Cumulative Proportion of Subjects Having Achieved Hemostasis at the Target Bleeding Site by Specified Time Points
timeFrame: From start of treatment until 4 minutes after treatment start
measure: Prevalence of Treatment Failures
timeFrame: From start of treatment up to surgical closure by layers of the exposed surgical field containing the TBS, a median of 34 minutes
Other outcomes:
Locations:
city: Tucson
country: United States
facility: 805
state: Arizona
city: Los Angeles
country: United States
facility: 602
state: California
city: Pasadena
country: United States
facility: 700, 801
state: California
city: Boulder
country: United States
facility: 803
state: Colorado
city: Hartford
country: United States
facility: 908
state: Connecticut
city: Washington, D.C.
country: United States
facility: 601
state: District of Columbia
city: Gainesville
country: United States
facility: 507
state: Florida
city: Jacksonville
country: United States
facility: 501, 901
state: Florida
city: Evanston
country: United States
facility: 604
state: Illinois
city: Lexington
country: United States
facility: 804
state: Kentucky
city: Baltimore
country: United States
facility: 905
state: Maryland
city: Jackson
country: United States
facility: 902
state: Mississippi
city: Las Vegas
country: United States
facility: 800
state: Nevada
city: New York
country: United States
facility: 600
state: New York
city: Poughkeepsie
country: United States
facility: 606
state: New York
city: Chapel Hill
country: United States
facility: 508
state: North Carolina
city: Fort Worth
country: United States
facility: 503
state: Texas
city: Houston
country: United States
facility: 900
state: Texas
city: Salt Lake City
country: United States
facility: 605
state: Utah
city: Spokane
country: United States
facility: 802
state: Washington
Study officials:
References:
citation: 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.