Inhibitor Development in Patients With Hemophilia A Undergoing Surgery

NCT01571934 | Completed

• 3 other identifiers: IRB000468005K23HL105785PASs
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

Hemophilia A is a genetic deficiency of factor VIII that causes blood to clot too slowly. The disease is classified based on how much factor VIII is in the blood. People with mild or moderate hemophilia A have low, but detectable, blood levels of factor VIII and bleed with trauma or surgery. At the time of surgery, they need to receive factor VIII replacement by infusion into the vein so that blood can clot normally and abnormal bleeding can be avoided. A complication of hemophilia A is the development of an antibody that binds factor VIII and makes the factor VIII infused for treatment not work properly. This antibody is called an inhibitor. In mild and moderate hemophilia A, inhibitors are not common, but have been reported to occur after intensive factor VIII infusions, as may occur at the time of surgery. This study is designed to observe people with mild and moderate hemophilia A who are having surgery. Information on the surgery, treatments given, bleeding, and infection will be gathered. Also, blood will be drawn to determine how the immune system is reacting to the factor VIII. No specific treatments will be given as part of this study. We will use the information to determine what influences inhibitor development. A better understanding of inhibitor development will help medical providers do things to avoid inhibitor development in this population or researchers to design new treatments.

Conditions

Hemophilia A

Keywords

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Inhibitor development (inhibitor titer > 0.4 BU/ml)

  Primary Study Endpoint: Inhibitor development (inhibitor titer \> 0.4 BU/ml) by post-operative (POD) day 90. Three months or 90 days was selected as the primary end point based on data collected in the case-control study where 17/18 cases had developed their inhibitor within 12 weeks of their intensive fVIII treatment and only 1 case developed the inhibitor \>16 weeks after the intensive fVIII treatment.

  postopereratvie date 90

Study Arms (1)

Mild or moderate hemophilia A

Subjects with mild or moderate hemophilia A (fVIII activity 1-40%) who are scheduled to undergo surgery for which at least 5 consecutive days of fVIII replacement therapy is required.

Eligibility Criteria

• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

In addition to Emory University, subjects will be recruited at one of 8 following sites: University of Pittsburgh, University of North Carolina, Oregon Health and Science University, University of Colorado, University of Texas Health Science Center at Houston, University of Minnesota, and Indiana Hemophilia Treatment Center.

You may qualify if:

• Males with mild/moderate hemophilia A (fVIII activity 1-40%)
• Planned surgical intervention which is anticipated to require 5 consecutive days of fVIII replacement therapy (These can be outpatient or inpatient treatment days.)
• Weight \>22.5 kg (To assure that volumes of blood to be drawn for study purposes are safe.)

You may not qualify if:

• Past history of an inhibitor (inhibitor titer \>0.4 BU/ml)
• HIV infection with CD4 count \<400/ul
• Currently receiving immunosuppressive medication(s)
• Unable to tolerate quantity of blood to be drawn
• Current or past diagnosis autoimmune disorder
• Current or past diagnosis of immune deficiency disorder other than HIV

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

University of Colorado, Hemophilia and Thrombosis Center

Aurora, Colorado, 80045, United States

Location

Emory University Comprehensive Hemophilia Treatment Center

Atlanta, Georgia, 30322, United States

Location

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7035, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh and Hemophilia Center of Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood drawn during study includes 15 ml within 7 days prior to surgery and 15 ml drawn on post-operative days 1, 14 and 90. Samples for DNA storage will be generated from blood draw study samples.

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Christine Kempton, MD, MSc

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Christine Kempton, MD, MSc

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 5, 2012
• Study Start: November 1, 2011
• Primary Completion: February 1, 2016
• Study Completion: March 1, 2016
• Last Updated: April 26, 2017

Record last verified: 2017-04

Locations

US (7)