Topical Raplixa for Surgical Bleeding in Children

A Phase 2, Randomized, Single-Blind, Controlled Trial of Topical Raplixa™ (Fibrin Sealant [Human]) in Intraoperative Surgical Hemostasis in a Pediatric Population

The purpose of the study is to determine if Raplixa plus Gelfoam is better than Gelfoam alone in stopping mild to moderate bleeding in children having surgery.

Study Overview

• Status: Terminated
• Conditions: Surgical Bleeding
• Intervention / Treatment: Drug: Raplixa; Device: Gelfoam; Drug: Rescue treatment

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
      • Arizona Burn Center at Maricopa Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Sacramento, California, United States, 95817
      • Shriners Hospital for Children
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Specialty Care
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann and Robert H Lurie Childrens Hospital of Chicago
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis Children's Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hospital for Children
    • Wayne, Pennsylvania, United States, 19087
      • SGM Physician Research Consortium, LLC
  • Texas
    • Dallas, Texas, United States, 90027
      • Children's Medical Center Dallas
  • Virginia
    • Roanoke, Virginia, United States, 24013
      • Carilion Clinic
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital - PIN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Before Surgery Inclusion Criteria:

• Was at least 36 weeks gestational age at birth (if an infant less than 6 months old) and is no older than 17 years at time of treatment
• Has a legal representative (parent or guardian) who signed an institutional review board (IRB)-approved informed consent document
• If at least 7 years old or appropriate age as defined by local regulations, may be required to sign an IRB-approved assent document
• Is scheduled to undergo one of the surgical procedures described in the protocol
• If female and of child-bearing potential, subject has negative pregnancy test on the day of surgery (baseline)
• If a sexually active male or female of reproductive potential, agrees to use a medically accepted form of contraception from the time of consent to completion of all follow-up study visits

During Surgery Inclusion Criteria:

• Has mild or moderate bleeding/oozing
• Has TBS surface area no more than 100 cm^2
• Has not received any whole blood, fresh frozen plasma (FFP), cryoprecipitate, or platelets within 24 hours prior to study drug (packed red blood cell (PRBC) transfusions are allowed)
• Had no complication during surgery other than bleeding which, in the opinion of the Investigator, may interfere with the assessment of efficacy or safety

Exclusion Criteria:

• Has any clinically significant laboratory or vital sign value, chronic disease state, or congenital coagulation disorder (eg, hemophilia A or B) that the investigator determines could interfere with the assessment of efficacy or pose a safety risk to the participant
• Is unwilling to receive blood products
• Has known antibodies or hypersensitivity to porcine gelatine, Raplixa or any of it's components, or other thrombin preparations or coagulation factors
• Has medical, social, or psychosocial factors that, in the opinion of the Investigator, could impact safety of the participant or compliance with study procedures, including protocol-defined limits on participating in other clinical studies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raplixa plus Gelfoam; During a single predefined surgical procedure, participants receive the assigned treatment on an appropriate target bleeding site (TBS). The treatment is topically applied using 1 of the following 3 methods: A thin layer of Raplixa is sprinkled directly from the vial onto the TBS, followed by application of Gelfoam.; A thin layer of Raplixa is sprayed onto the TBS using the RaplixaSpray device, followed by application of Gelfoam.; Raplixa is applied onto moistened Gelfoam which is then applied to the TBS. Manual pressure is applied over the treatments using sterile gauze. The amount of Raplixa and Gelfoam used is at the discretion of the investigator, within the maximum of two 1 gram (g) vials of Raplixa that are permitted for each participant. Thrombin-containing hemostats included in standard of care at the site are permitted as rescue therapy after the 5-minute time-to-hemostasis (TTH) evaluation.	Drug: Raplixa; Raplixa is a biological product approved for use in adults to help control bleeding from small blood vessels when standard surgical techniques, such as suture, ligature or cautery, are ineffective or impractical. When applied to a bleeding site, Raplixa is dissolved in the blood and a reaction starts between the fibrinogen and thrombin proteins. This results in the formation of blood clots to help stop the bleeding.; Other Names: Fibrin Sealant [Human]; Fibrocaps; Device: Gelfoam; Gelfoam Sterile Sponge is a medical device (USP, Pfizer) intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product. It may be cut without fraying, used wet or dry, and is able to absorb many times its weight in blood and other fluids.; Other Names: Gelfoam 50; Gelfoam 100; Drug: Rescue treatment; Thrombin-containing hemostats included in standard care at the site; Other Names: Standard Care
Other: Gelfoam Only; During a single predefined surgical procedure, participants receive the assigned treatment on an appropriate TBS. Gelfoam is cut to the appropriate size and applied topically, according to the manufacturer's package insert, followed by manual pressure using sterile gauze. Thrombin-containing hemostats included in standard of care at the site are permitted as rescue therapy after the 5-minute TTH evaluation, if necessary.	Device: Gelfoam; Gelfoam Sterile Sponge is a medical device (USP, Pfizer) intended for application to bleeding surfaces as a hemostatic. It is a water-insoluble, off-white, nonelastic, porous, pliable product. It may be cut without fraying, used wet or dry, and is able to absorb many times its weight in blood and other fluids.; Other Names: Gelfoam 50; Gelfoam 100; Drug: Rescue treatment; Thrombin-containing hemostats included in standard care at the site; Other Names: Standard Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Reached Hemostasis at the Target Bleeding Site (TBS) Within 4 Minutes	Count of Participants who Reached Hemostasis at the TBS within 4 minutes of the first study drug application	within 4 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Reached Hemostasis at the TBS Within 5 Minutes	Count of Participants who Reached Hemostasis at the TBS within 5 minutes of the first study drug application	within 5 minutes
Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs)	Clinically significant changes in safety measures are recorded as adverse events. Participants with TEAEs that are deemed by the principal investigator or the independent data monitoring committee as possibly or definitely treatment-related (including device-related) are included in the count for this secondary outcome measure.	within 97 days

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2014
• Primary Completion (Actual): November 17, 2017
• Study Completion (Actual): March 6, 2018

Study Registration Dates

• First Submitted: April 14, 2014
• First Submitted That Met QC Criteria: April 15, 2014
• First Posted (Estimate): April 17, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: bleeding; fibrinogen; fibrin sealant; surgical hemostasis; thrombin; spray dried
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage; Hemostatics; Coagulants; Fibrin Tissue Adhesive; Gelatin Sponge, Absorbable
• Other Study ID Numbers: FC-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No