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ADVATE Hemophilia A Outcome Database (AHEAD) (AHEAD)

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ClinicalTrials.gov Identifier: NCT02078427
Recruitment Status : Recruiting
First Posted : March 5, 2014
Last Update Posted : December 21, 2017
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
The purpose of the study is to document the natural history of hemophilia. A disease and long-term outcomes in terms of effectiveness, safety and quality of life (QoL) in participants receiving ADVATE in routine clinical practice. Participants may use any treatment regimen, including on-demand and prophylaxis using standardized regimens or individual pharmacokinetic (PK)-guided dosing regimens, or immune tolerance induction (ITI) therapy, as determined by the treating physician.

Condition or disease Intervention/treatment
Hemophilia A Biological: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method

Study Type : Observational
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: ADVATE Hemophilia A Outcome Database
Study Start Date : June 1, 2011
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2019



Intervention Details:
  • Biological: Antihemophilic Factor (Recombinant) - Plasma/Albumin Free Method
    Other Name: ADVATE


Primary Outcome Measures :
  1. Joint health outcomes - assessed by physical exam using only the pain, bleeding, and physical exam parameters of the Gilbert Scale. [ Time Frame: 4 years ]

    The World Federation of Hemophilia developed a musculoskeletal evaluation system, commonly referred to as the Gilbert test, to measure hemophilia joint health status.The Gilbert test needs to be performed in the absence of acute bleed, acute pain, and acute inflammation into the evaluated joint.

    Four parameters are used in each Gilbert test: pain (score: 0-3), bleeding (score: 0-3), physical exam (score: 0-12), and X-ray evaluation (score: 0-13)

    Scores of 0, represent no pain, no bleeding, no physical exam issues, and/or no x-ray issues. Higher scores for each of these categories represents worsening conditions.



Secondary Outcome Measures :
  1. Annualized bleed rate, all joints [ Time Frame: 4 years ]
    The annualized bleed rate for all joints will be calculated per participant and summarized over the set of available participants.

  2. Annualized bleed rate, all bleeds [ Time Frame: 4 years ]
    The annualized bleed rate for all bleeds will be calculated per participant and summarized over the set of available participants.

  3. Annualized bleed rate, pre-existing target joints at baseline [ Time Frame: 4 years ]
    The annualized bleed rate for pre-existing target joints at baseline will be calculated per participant and summarized over the set of available participants.

  4. Incidence of New Target Joints [ Time Frame: 4 years ]
    The incidence of new target joints will be calculated as the total number of new target joints in all participants divided by the total number of observation days. The time to the first occurrence of a new target joint in a participant will be analyzed by the Kaplan-Meier technique.

  5. Status of joint health by X-ray by Pettersson scale [ Time Frame: 4 years ]
    The status of joint health by X-ray by Pettersson score will be summarized for timepoints 0, 1, 2, 3, and 4 years after study start. Linear interpolation (for any time interval) and linear extrapolation (for up to 0.5 years) will be used to derive an estimate of the score at these timepoints.

  6. Status of Joint Health by Magnetic Resonance Imaging (MRI) Scoring System- Using The Lund Scoring System (LSS) [ Time Frame: 0, 1, 2, 3, and 4 years ]

    LSS score format= A(e:s:h). Sum of values for Subchondral Cyst (score: 1-6), irregularity/erosion of Subchondral Cortex (score: 1-4), and Chondral Destruction (score: 1-6) gives value for the A component of score. e, s, h components represent effusion/hemarthrosis, hypertrophic synovial, & hemosiderin deposition (score: 0-4 for each). Max. score is 16(4:4:4).

    Subchondral Cyst:

    • ≥1 bone
    • ≥2 bones
    • >3 cysts in ≥1 bone
    • >3 cysts ≥2 bones
    • Largest size >4 mm: ≥1 bone
    • Largest size >4 mm: ≥2 bones

    Subchondral Cortex

    • ≥1 bone
    • ≥2 bones
    • Involve > half joint surface: ≥1 bone
    • Involve > half of joint surface: ≥2 bones

    Chondral Destruction

    • ≥1 bone
    • ≥2 bones
    • Full thickness defect (FTD): ≥1 bone
    • FTD: ≥2 bones
    • FTD involves >1/3 of joint surface: ≥1 bone
    • FTD involves >1/3 of joint surface: ≥2 bones

    Effusion/hemarthrosis (e): Hypertrophic synovial (s): Hemosiderin (h): (0-4 for each):

    • 0 absent
    • 1 equivocal
    • 2 small
    • 3 moderate
    • 4 large

  7. Status of joint health using the Hemophilia Joint Health Score (HJHS) [ Time Frame: 0, 1, 2, 3, and 4 years ]

    The International Prophylaxis Study Group (IPSG) developed a scoring system for musculoskeletal evaluation, the HJHS, optimized for use in children with no or minimal joint disease.

    The HJHS includes the following parameters: swelling, duration of swelling, muscle atrophy, joint pain, crepitus on motion, flexion loss, extension loss, strength and global gait.


  8. Overall effectiveness assessment for prophylaxis therapy [ Time Frame: 4 years, Throughout the study ]
    • Excellent: Same or lower breakthrough bleed rate (BBR) within last 12 months (M) compared with previous prophylaxis; if participant did not receive previous prophylaxis with rAHF-PFM or another Factor VIII (FVIII), same or better than expected outcome according to investigator's expectation
    • Good: Minor increase in BBR within last 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, slightly less than expected outcome according to investigator's expectation
    • Fair: Moderate increase in BBR in last 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, somewhat less than expected outcome according to investigator's expectation
    • Poor: Significant increase in BBR in the 12M compared with previous prophylaxis; if participant did not receive prophylaxis with rAHF-PFM or another FVIII, little to no benefit according to investigator's expectation

  9. Overall effectiveness assessment for on-demand treatment [ Time Frame: 4 years, Throughout the study ]
    • Excellent: Bleed episodes typically respond to same or fewer number of infusion and same or lower dose as compared with previous on-demand treatment or investigator's expectation
    • Good: Most bleed episodes typically respond to same number of infusion and dose but some require more infusions or higher dose as compared with previous on-demand treatment or investigator's expectation
    • Fair: Bleed episodes typically require more infusions and/or higher dose than expected as compared with previous on-demand treatment or investigator's expectation
    • Poor: Bleed episodes routinely fail to respond to same number of infusion and dose and require additional or different factor concentrate for hemostatic control as compared with previous on-demand treatment or investigator's expectation

  10. Global effectiveness assessment for on-demand treatment [ Time Frame: 4 years, Throughout the study ]
    • Excellent: Full relief of pain and cessation of bleeding as evidenced by objective signs (e.g., swelling, tenderness, irritability, inconsolability, and decreased range of motion in the case of musculoskeletal hemorrhage) within approximately 8 hours of a single infusion. No additional infusion is required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring.
    • Good: Definite pain relief and/or improvement in signs of bleeding within approximately 8 hours after the infusion. Possibly requires more than 1 infusion for complete resolution.
    • Fair: Probable or slight relief of pain and slight improvement in signs of bleeding within approximately 8 hours after the infusion. Requires more than 1 infusion for complete resolution.
    • Poor: No improvement or condition worsens.

  11. Number of ADVATE units required for bleed cessation [ Time Frame: 4 years, Throughout the study ]
  12. Number of ADVATE infusions required for bleed cessation [ Time Frame: 4 years, Throughout the study ]
  13. Incidence of target joint intervention, including surgery, radiosynovectomy, and chemosynovectomy [ Time Frame: 4 years, Throughout the study ]
  14. Incidence of pseudo tumor development [ Time Frame: 4 years, Throughout the study ]
  15. Quality of Life: HAL questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The HAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for adults.

  16. Quality of Life: SF-12v2 questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The SF-12v2 measures generic health-related quality of life for adults.

  17. Quality of Life: EQ-5D questionnaire - for adult patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The EQ-5D measures health utility in subjects aged 13 and up.

  18. Quality of Life: PedHAL questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]

    The PedHAL measures activities involving the upper extremities, basic activities involving the lower extremities and complex activities involving the lower extremities as well as an overall physical activity score for children.

    For participants 4-13 years of age:

    - PedHAL (parent version)

    For participants 14-17 years of age:

    - PedHAL (child version)


  19. Quality of Life: SF-10 questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The SF-10 measures generic health-related quality of life for children and is parent-completed.

  20. Quality of Life: EQ-5D (13 and up) questionnaire - for pediatric patients [ Time Frame: 0, 1, 2, 3, and 4 years ]
    The EQ-5D measures health utility in subjects aged 13 and up.

  21. Chronic pain associated with hemophilia, as measured over a period of 4 weeks on an annual basis, using the visual analog scale (VAS) [ Time Frame: Year 0, 1, 2, 3 and 4 ]

    The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).

    During screening visit and on an annual basis, the investigators shall ask participants to rate the average level of chronic pain associated with hemophilia over the period of 4 weeks prior to visit date using the VAS.


  22. Acute pain associated with hemophilia, as measured with individual bleeding episodes, using the visual analog scale (VAS) [ Time Frame: Year 1, 2, 3 and 4 ]

    The VAS assesses the pain using a scale of 0 (no pain) to 10 (unbearable pain).

    Participants will be asked to provide ratings on level of acute pain associated with each bleeding episode using the VAS. The VAS scores will be recorded in the participant diary.


  23. Number of days lost from school or work due to bleeding episodes [ Time Frame: Year 1, 2, 3 and 4 ]
  24. Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% without history of inhibitor [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  25. Incidence of Inhibitors in Previously Treated Patients (PTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% with history of inhibitor [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  26. Incidence of Inhibitors in Previously Untreated Patient (PUPs) and Minimally Treated Patients (MTPs) with Factor VIII (FVIII) Levels <1%, ≤2%, and ≤5% [ Time Frame: Year 0, 1, 2, 3 and 4 ]
  27. Incidence of therapy-related serious adverse events [ Time Frame: 4 years, Throughout the study ]
  28. Incidence of therapy-related non-serious adverse events [ Time Frame: 4 years, Throughout the study ]


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
The study population will include male and female participants of any race and age who have a diagnosis of hemophilia A (Factor VIII (FVIII) =5%). Participants must have been prescribed ADVATE for the management of hemophilia A by the treating physician prior to the decision to enroll in the study.
Criteria

Inclusion Criteria:

  • Participant has hemophilia A (Factor VIII (FVIII) ≤5%)
  • Participant is prescribed ADVATE by the treating physician
  • Participant or participant's legally authorized representative provides informed consent

Exclusion Criteria:

  • Participant has known hypersensitivity to the active substance or any of the excipients
  • Participant has known allergic reaction to mouse or hamster proteins
  • Participant has participated in another clinical study involving an investigational product (IP) or device within 30 days prior to study enrollment or is scheduled to participate in another clinical study involving another FVIII concentrate or device during the course of this study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02078427


Contacts
Contact: Manfred Pirck manfred.pirck@shire.com

  Show 94 Study Locations
Sponsors and Collaborators
Baxalta now part of Shire
Investigators
Study Director: Alessandro Gringeri, MD, PhD Baxalta Innovations GmbH, now part of Shire

Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02078427     History of Changes
Other Study ID Numbers: 061001
First Posted: March 5, 2014    Key Record Dates
Last Update Posted: December 21, 2017
Last Verified: December 2017

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