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

24 april 2017 bijgewerkt door: Christine Kempton, MD, MSc, Emory University
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.

Studie Overzicht

Toestand

Voltooid

Conditie

Gedetailleerde beschrijving

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.

Studietype

Observationeel

Inschrijving (Werkelijk)

30

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Colorado
      • Aurora, Colorado, Verenigde Staten, 80045
        • University of Colorado, Hemophilia and Thrombosis Center
    • Georgia
      • Atlanta, Georgia, Verenigde Staten, 30322
        • Emory University Comprehensive Hemophilia Treatment Center
    • Indiana
      • Indianapolis, Indiana, Verenigde Staten, 46260
        • Indiana Hemophilia and Thrombosis Center
    • North Carolina
      • Chapel Hill, North Carolina, Verenigde Staten, 27599-7035
        • University of North Carolina
    • Oregon
      • Portland, Oregon, Verenigde Staten, 97239
        • Oregon Health & Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Verenigde Staten, 15213
        • University of Pittsburgh and Hemophilia Center of Pennsylvania
    • Texas
      • Houston, Texas, Verenigde Staten, 77030
        • The University of Texas Health Science Center at Houston

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Kind
  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Mannelijk

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

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.

Beschrijving

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)
  • 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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Inhibitor development (inhibitor titer > 0.4 BU/ml)
Tijdsspanne: postopereratvie date 90
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

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Emory University

Medewerkers

National Heart, Lung, and Blood Institute (NHLBI)
National Institutes of Health (NIH)

Onderzoekers

  • Hoofdonderzoeker: Christine Kempton, MD, MSc, Emory University

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 november 2011

Primaire voltooiing (Werkelijk)

1 februari 2016

Studie voltooiing (Werkelijk)

1 maart 2016

Studieregistratiedata

Eerst ingediend

4 april 2012

Eerst ingediend dat voldeed aan de QC-criteria

4 april 2012

Eerst geplaatst (Schatting)

5 april 2012

Updates van studierecords

Laatste update geplaatst (Werkelijk)

26 april 2017

Laatste update ingediend die voldeed aan QC-criteria

24 april 2017

Laatst geverifieerd

1 april 2017

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • IRB00046800
  • PASS (Other)
  • 5K23HL105785 (Subsidie/contract van de Amerikaanse NIH)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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