Hemophilia Adult Prophylaxis Study

This study is currently recruiting participants.
Verified August 2012 by University of Pittsburgh
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Margaret Ragni, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01405742
First received: July 25, 2011
Last updated: August 5, 2012
Last verified: August 2012

July 25, 2011
August 5, 2012
July 2012
December 2013   (final data collection date for primary outcome measure)
The primary outcome measure is bleeding frequency. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01405742 on ClinicalTrials.gov Archive Site
  • A secondary outcome measure is factor usage and cost. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
  • A secondary outcomes is joint range of motion. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
  • A secondary outcome is inter-dose hypocoagulability by thrombin generation. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: No ]
  • A secondary outcome measure is F.VIII and inhibitor formation. [ Time Frame: The time frame is 52 weeks per subject. ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Hemophilia Adult Prophylaxis Study
R34 Pilot Feasibility Randomized, Noninferiority, Cross-Over Trial of Once-Weekly vs. Thrice-Weekly Prophylaxis With Recombinant Factor VIII in Adults With Severe Hemophilia A

The purpose of this pilot R34 trial is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis comparing once weekly with thrice-weekly recombinant factor VIII. Efficacy will measured by bleeding frequency, factor usage, joint range of motion, cost, quality-of-life, F.VIII level, and inter-dose hypocoagulability by thrombin generation. Safety will be measured by inhibitor formation and bleeding events unresponsive to up to two rescue doses.

The purpose of this 52-week pilot R34 randomized, open-label, non-inferiority, cross-over study is to determine the feasibility of a large single dose Phase III study of hemophilia adult prophylaxis. The primary efficacy endpoint will be bleeding frequency. Secondary endpoints will include factor usage, joint range of motion, cost, quality-of-life, and inter-dose hypocoagulability by thrombin generation time and F.VIII activity will also be determined. Safety will be measured by the frequency of bleeding unresponsive to up to two rescue treatments. Inhibitor formation by anti-F.VIII Bethesda assay, and clinical frequency of thrombosis and allergic reactions will also be assessed. Subject acceptance and adherence to the treatment interventions will be determined; and web-based data entry of case report forms, digital range-of-motion images, and quality-of-life instrument will be implemented. The relation of bleeding frequency to relative inter-dose hypocoagulability, will be assessed by inter-dose thrombin generation time (TGT), endogenous thrombin potential (ETP), and factor VIII levels. Optimal blood sample collection and shipping methods will be determined. For all tests, we will estimate and determine completeness and congruency, in order to determine adjustments or revisions required before initiating a large phase III Randomized clinical trial. All testing will be exploratory, so that we may determine if the test, approach are realistic, and to estimate standard deviations for future power analyses.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Severe Hemophilia A
  • Drug: Recombinant factor VIII
    In this arm, 40 IU/kg recombinant factor VIII will be given thrice-weekly by intravenous injection for 26 weeks. At 26 weeks after a 4-day washout period, 40 IU/kg recombinant factor VIII will be given once-weekly by intravenous injection until week 52, with up to two rescue doses per week for bleeds.
  • Drug: Recombinant factor VIII
    In this arm, 40 IU/kg recombinant factor VIII will be given once-weekly by intravenous injection for 26 weeks, with up to two rescue doses per week for bleeds. At 26 weeks after a 4-day washout period, 40 IU/kg recombinant factor VIII will be given thrice-weekly by intravenous injection until week 52.
  • Experimental: Arm A: rF.VIII once then thrice weekly
    Intervention: Drug: Recombinant factor VIII
  • Experimental: Arm B: r.FVIII thrice then once weekly
    Intervention: Drug: Recombinant factor VIII
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
February 2014
December 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult males 18 years or older
  • Severe hemophilia A (F.VIII < 0.01 U/ml)
  • At least 150 exposure days to F.VIII products
  • No detectable inhibitor
  • No history of allergic reaction
  • Platelets at least 150,000/ul
  • If HIV(+), CD4 at least 200/ul, HIV-VL <48 copies/ml,and cART compliant
  • If HCV(+), no splenomegaly,varices,GI bleed,ascites,edema,encephalopathy
  • Willingness to comply with cross-over design, randomization schema
  • Willingness to keep a personal diary of bleeding frequency and factor use
  • Willingness to make every 3 month visits, coagulation testing at wks 2, 28

Exclusion Criteria:

  • Acquired hemophilia
  • Any bleeding disorder other than hemophilia A
  • Presence of an inhibitor to factor VIII
  • Historic platelet count < 100,000
  • Use of experimental drugs
  • Surgery anticipate in the next 52 weeks
  • Symptomatic HCV(splenomegaly,varices,GI bleed,ascites,edema,encephalopathy)
  • Symptomatic HIV(CD4<200/ul or HIV VL 48 or more copy/ml,cART noncompliant)
  • Life expectancy less than 5 years
  • Investigational drug or study within 4 weeks prior to study
  • Inability to comply with study requirements
Male
18 Years and older
No
Contact: Margaret V. Ragni, MD, MPH 412-209-7288 ragni@dom.pitt.edu
Contact: Kristen Jaworski, BSN, RN 412-209-7411 kjaworski@itxm.org
United States
 
NCT01405742
PRO10020178
Yes
Margaret Ragni, University of Pittsburgh
University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Margaret V. Ragni, MD, MPH University of Pittsburgh
University of Pittsburgh
August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP