Inhibitor Development in Patients With Hemophilia A Undergoing Surgery (PASs)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Emory University
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Christine Kempton, MD, MSc, Emory University
ClinicalTrials.gov Identifier:
NCT01571934
First received: April 4, 2012
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

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.


Condition
Hemophilia A

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Inhibitor Development in Patients With Hemophilia A Undergoing Surgery

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Inhibitor development (inhibitor titer > 0.4 BU/ml) [ Time Frame: postopereratvie date 90 ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples With DNA

Blood drawn during study includes 30 ml within 7 days prior to surgery and 30 ml drawn on post-operative days 7, 30 and 90.

Samples for DNA storage: 30 ml of blood drawn four separate times around the time of a subject's planned surgery


Estimated Enrollment: 140
Study Start Date: November 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

Detailed Description:

The development of neutralizing anti-factor VIII (fVIII) antibodies, fVIII inhibitor, is the most significant complication affecting patients with hemophilia A (HA). Once an inhibitor develops, treatment is less effective and costly. Although inhibitors occur most commonly in those with severe HA, 25% of new inhibitors occur in those with non-severe HA. In patients with non-severe HA, the development of a fVIII inhibitor can change the course of disease from one that is easily managed to one with the potential for spontaneous life-threatening difficult to treat bleeding. Although significant advances have been made in understanding risk factors for fVIII inhibitor development in patients with severe HA, studies that seek to understand the risk for fVIII inhibitor development in those with non-severe disease have been limited to retrospective analyses. In these retrospective analyses, intensive fVIII treatment and surgery have been identified as risk factors for fVIII inhibitor development in non-severe HA. Additionally, receiving fVIII by continuous infusion has been associated with fVIII inhibitor development in non-severe HA in some but not all studies and may be due in part to a more robust proinflammatory response during continuous infusion. Accordingly, the next logical step to evaluate the risk of inhibitor development associated with continuous fVIII infusion is a prospective observational cohort study. Additionally, knowledge of the immune response to fVIII in the surgical setting is essential for identification of patients at high risk for inhibitor development and development of strategies to prevent inhibitor development and is best evaluated in the setting of an prospective cohort study.

This multicenter prospective observational cohort study will enroll a total of 140 subjects at 10 centers who have 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. The study will gather clinical data and collect blood specimens on 4 occasions over a 3 month period. Outcomes include: inhibitor development, total fVIII usage, bleeding, and markers of T cell activation.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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, Tulane University, 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.

Criteria

Inclusion Criteria:

  • 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.)

Exclusion Criteria:

  • Past history of an inhibitor (inhibitor titer >0.4 BU/ml)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01571934

Contacts
Contact: Christine Kempton, MD, MSc (404) 727-1608 christine.kempton@emory.edu

Locations
United States, Colorado
University of Colorado, Hemophilia and Thrombosis Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Saeed Gholizadeh    303-724-0692    saeed.gholizadeh@ucdenver.edu   
Contact: Kristin Norton    (303) 724-0363    kristi.norton@ucdenver.edu   
Principal Investigator: Jorge Di Paola         
United States, Georgia
Emory University Comprehensive Hemophilia Treatment Center Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kesley Tyson    404-785-9856    kdtyson@emory.edu   
Principal Investigator: Christine Kempton, MD, MSc         
United States, Indiana
Indiana Hemophilia and Thrombosis Center Recruiting
Indiannapolis, Indiana, United States, 46260
Contact: Jackie Buckley    317-871-0011 ext 296    jbuckley@ihtc.org   
Principal Investigator: Amy Shapiro, MD         
United States, Louisiana
Tulane University Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Amy Kinzie    504-988-5433    akinzie@tulane.edu   
Principal Investigator: Rebecca Kruse-Jarres, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55255
Contact: Joan Osip    612-626-2450    josip1@fairview.org   
Principal Investigator: Mark Reding, MD         
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599-7035
Contact: Brenda Nielsen    919-966-4736    nielsen@med.unc.edu   
Principal Investigator: Nigel Key, MD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Kathy Beach    503-494-7425    beachk@ohsu.edu   
Principal Investigator: Michael Recht, MD, PhD         
United States, Pennsylvania
University of Pittsburgh and Hemophilia Center of Pennsylvania Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Kathy Betts    412-209-7563    kbetts@itxm.org   
Principal Investigator: Magaret Ragni, MD, MPH         
United States, Texas
The University of Texas Health Science Center at Houston Recruiting
Houston, Texas, United States, 77030
Contact: Madeline Cantini    713-500-8377    madeline.cantini@uth.tmc.edu   
Contact: Kris Cannon    713-500-8352    krishna.cannon@uth.tmc.edu   
Principal Investigator: Miguel Escobar, MD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Christine Kempton, MD, MSc Emory University
  More Information

No publications provided

Responsible Party: Christine Kempton, MD, MSc, Emory University
ClinicalTrials.gov Identifier: NCT01571934     History of Changes
Other Study ID Numbers: IRB00046800, 5K23HL105785, PASs
Study First Received: April 4, 2012
Last Updated: May 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Hemophilia A

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014