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Trial record 10 of 456 for:    Inherited Bleeding Disorder

Personalized Prophylactic Treatment With Advate® in Severe or Moderate Haemophilia A Patients

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ClinicalTrials.gov Identifier: NCT02622646
Recruitment Status : Unknown
Verified August 2016 by José Luis Poveda Andrés, Hospital Universitario La Fe.
Recruitment status was:  Recruiting
First Posted : December 4, 2015
Last Update Posted : August 17, 2016
Sponsor:
Information provided by (Responsible Party):
José Luis Poveda Andrés, Hospital Universitario La Fe

Brief Summary:

Haemophilia A is an inherited bleeding disorder caused by a deficiency of factor VIII (FVIII). Patients with severe hemophilia A have a FVIII plasma concentration less than1 IU/dL and experience spontaneous and trauma-induced bleeds. Joint bleeds lead to hemophilic arthropathy resulting in progressive disability. Patients with moderate hemophilia (FVIII level between 1-5 IU/dL) are characterized by fewer hemarthroses, usually trauma-induced, and a decreased likelihood of developing arthropathy. This clinical observation led to the use of prophylactic FVIII infusions to convert patient´s bleeding phenotype from severe to moderate with the result of decreasing or preventing arthropathy.

Prophylactic regimens may be effective when based on standard fixed-dose protocols (that assumes one approach fits all patients) or phenotypic dosing determined by bleeding patterns, but do not protect all patients with severe haemophilia from joint damage caused by spontaneous or activity-triggered bleeding.

Individualized treatment in haemophilia A takes into consideration all available information about the patient, not only his phenotypic bleeding pattern. Some of the factors that contribute to the observed interpatient variability include baseline or residual FVIII activity, the pharmacokinetic (PK) profile of the replacement factor, the individual's level of physical activity and perceived risk of traumatic bleeding, the presence or absence of joint disease, presence of comorbidities and adherence to the dosing regimen.

Objectives:

Identify and analyze cause(s) of poor bleeding control in patients on prophylaxis treatment and study the clinical impact of a "personalized pilot program" with a 1 year follow up to act on the specific causes.

  1. Describe PK parameters in patients on prophylaxis treatment with Advate®.
  2. Analyze differences in PK parameters in non-controlled vs well controlled patients.
  3. Identify causes of poor clinical outcome in non-controlled patients. Patients' individual variables that influence bleeding risk will be studied (individual PK, bleeding pattern, joint status, physical activity, life style and patient's adherence).
  4. Study the improvement in clinical outcomes (ABR and Joint status) of a 1 year Personalized Prophylaxis Program that acts specifically on the previously identified causes of bleeding in non-controlled patients (named: short half-life, high bleeding pattern, joint damage, high risk physical activity, active life style and poor patient's adherence).

Condition or disease Intervention/treatment
Hemophilia A Factor VIII Drug: Recombinant VIII factor

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 25 participants
Time Perspective: Prospective
Official Title: Personalized Prophylactic Treatment With Advate® in Severe or Moderate Haemophilia A Patients
Study Start Date : August 2016
Estimated Primary Completion Date : February 2018
Estimated Study Completion Date : February 2018


Group/Cohort Intervention/treatment
Well controlled patients
Patients with an adequate disease control with the routine clinical practice (AJBR≤2, non-severe ABR≤5 and severe ABR≤2) (Ministerio de Sanidad, Servicios Sociales e Igualdad. Gobierno de España; 2012)
Drug: Recombinant VIII factor

Identify and analyze cause(s) of poor bleeding control in patients on prophylaxis treatment and study the clinical impact of a "personalized pilot program" with a 1 year follow up to act on the specific causes.

  1. Describe PK parameters in patients on prophylaxis treatment with Advate®
  2. Analyze differences in PK parameters in non-controlled vs well controlled patients
  3. Identify causes of poor clinical outcome in non-controlled patients. Patients' individual variables that influence bleeding risk will be studied (individual PK, bleeding pattern, joint status, physical activity, life style and patient's adherence).
  4. Study the improvement in clinical outcomes (ABR and Joint status) of a 1 year Personalized Prophylaxis Program that acts specifically on the previously identified causes of bleeding in non-controlled patients (named: short half-life, high bleeding pattern, joint damage, high risk physical activity, active life style and poor patient's adherence).

Poor controlled patients
Patients with poor disease control, based on the international guidelines: AJBR>2, ABR>2 for severe BE or ABR >5 for non-severe BE
Drug: Recombinant VIII factor

Identify and analyze cause(s) of poor bleeding control in patients on prophylaxis treatment and study the clinical impact of a "personalized pilot program" with a 1 year follow up to act on the specific causes.

  1. Describe PK parameters in patients on prophylaxis treatment with Advate®
  2. Analyze differences in PK parameters in non-controlled vs well controlled patients
  3. Identify causes of poor clinical outcome in non-controlled patients. Patients' individual variables that influence bleeding risk will be studied (individual PK, bleeding pattern, joint status, physical activity, life style and patient's adherence).
  4. Study the improvement in clinical outcomes (ABR and Joint status) of a 1 year Personalized Prophylaxis Program that acts specifically on the previously identified causes of bleeding in non-controlled patients (named: short half-life, high bleeding pattern, joint damage, high risk physical activity, active life style and poor patient's adherence).




Primary Outcome Measures :
  1. Steady state volume (Vss) [ Time Frame: At baseline and at 12 months ]

    This PK parameter of FVIII will be evaluated for each patient using the Bayesian pharmacokinetic 2-compartment model described by Björkman (MyPkFit ®). This model needs at least two samples:

    • First sample: at 3 hours of the administration.
    • Second sample: between 24-32 hours post-infusion. FVIII is measured by the one-stage assay in a central laboratory. PK monitoring will be performed in all the routine medical visits, at least two visits per year.

  2. Clearance (Cl) [ Time Frame: At baseline and at 12 months ]

    This PK parameter of FVIII will be evaluated for each patient using the Bayesian pharmacokinetic 2-compartment model described by Björkman (MyPkFit ®). This model needs at least two samples:

    • First sample: at 3 hours of the administration.
    • Second sample: between 24-32 hours post-infusion. FVIII is measured by the one-stage assay in a central laboratory. PK monitoring will be performed in all the routine medical visits, at least two visits per year.

  3. Half-life of FVIII (t½) [ Time Frame: At baseline and at 12 months ]

    This PK parameter of FVIII will be evaluated for each patient using the Bayesian pharmacokinetic 2-compartment model described by Björkman (MyPkFit ®). This model needs at least two samples:

    • First sample: at 3 hours of the administration.
    • Second sample: between 24-32 hours post-infusion. FVIII is measured by the one-stage assay in a central laboratory. PK monitoring will be performed in all the routine medical visits, at least two visits per year.

  4. Time to 1% FVIII activity above [ Time Frame: At baseline and at 12 months ]

    This PK parameter of FVIII will be evaluated for each patient using the Bayesian pharmacokinetic 2-compartment model described by Björkman (MyPkFit ®). This model needs at least two samples:

    • First sample: at 3 hours of the administration.
    • Second sample: between 24-32 hours post-infusion. FVIII is measured by the one-stage assay in a central laboratory. PK monitoring will be performed in all the routine medical visits, at least two visits per year.

  5. Annualized bleeding rate (ABR) [ Time Frame: At baseline, at 6 months and at 12 months ]
    To measure the bleeding pattern of each patient the annualized bleeding rate (ABR) will be employed. A subgroup analysis will be performed by bleeding type to determine numbers of traumas and spontaneous bleeds.

  6. Annualized joint bleeding rate (AJBR) [ Time Frame: At baseline, at 6 months and at 12 months ]
    To measure the bleeding pattern of each patient the annualized joint bleeding rate (AJBR) will be employed. A subgroup analysis will be performed by bleeding type to determine numbers of traumas and spontaneous bleeds.

  7. Gilbert joint score [ Time Frame: At baseline and at 12 months ]
    To measure the joint status of each patient the Gilbert joint score will be employed.

  8. HJHS score [ Time Frame: At baseline and at 12 months ]
    To measure the joint status of each patient the HJHS score will be employed..

  9. Physical activity [ Time Frame: At baseline, at 6 months and at 12 months ]

    The physical activity will be broadly categorized using a modification of the taxonomy devised by the American National Hemophilia Foundation (Broderick et al. JAMA 2012, Fischer et al. Haemophilia 2014).

    • Category 1 activities: are activities in which significant collisions are not expected (eg, swimming).
    • Category 2 activities: are those in which significant collisions might occur (eg, basketball).
    • Category 3 activities: are those in which significant collisions are inevitable (eg, wrestling).

  10. Adherence [ Time Frame: At baseline and at 12 months ]
    To quantify the adherence, adherence index (AI) will be calculated as the units administered divided by the units prescribed, multiplied by one hundred. Then the difference between this value and the perfect percentage of adhesion (100%) will be calculated. The result is the difference in percentage points the patient moves away from ideal adhesion. Adherence is based on data recorded in medical history of the patients and in their pharmacy dispensation records (García-Dasí et al. Haemophilia 2015).

  11. Quality of life [ Time Frame: At baseline and at 12 months ]
    The A36 Hemofilia-QoL questionnaire will be used to measure quality of life perceived by patients at the beginning and end of the study.

  12. FVIII consumption [ Time Frame: At baseline and at 12 months ]
    The amount of FVIII concentrate used and the corresponding cost will be calculated at the beginning and end of the study.

  13. FVIII inhibitors [ Time Frame: At baseline and at 12 months ]
    Assessment of FVIII inhibitor development is included in the safety analyses (and exclusion criteria) and will be performed at baseline and in all the routine medical visits, using the Bethesda Assay.


Biospecimen Retention:   Samples With DNA
FVIII is measured by the one-stage assay in a central laboratory in complete blood samples


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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Haemophilia A severe (FVIII < 1 IU/dL) or moderate (FVIII 1 ≤5 IU/dL) in adult or adolescent patients in prophylactic treatment with Advate®.
Criteria

Inclusion Criteria:

  • Adults or adolescents older than 12 years
  • Patients under Prophylactic treatment with Advate® for at least 1 year
  • Written informed consent.

Exclusion Criteria:

  • History of FVIII inhibitor (titre ≥ 0.6 BU [Bethesda unit]) or detectable FVIII inhibitors at screening (titre ≥ 0.4 BU),
  • Another haemostatic defect
  • Need for major surgery.
  • Withdrawal of informed consent

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): NCT02622646


Locations
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Spain
Hemostasis and Thrombosis Department, Hospital Universitari i Politecnic La Fe, Valencia, Spain. Recruiting
Valencia, Spain, 46026
Contact: Juan Eduardo Megías Vericat, Hospital Pharmacist    +34 961244985    megias_jua@gva.es   
Sponsors and Collaborators
Hospital Universitario La Fe

Publications of Results:

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Responsible Party: José Luis Poveda Andrés, Director of Drug Clinical Area, Hospital Universitari i Politecnic La Fe, Valencia, Spain., Hospital Universitario La Fe
ClinicalTrials.gov Identifier: NCT02622646     History of Changes
Other Study ID Numbers: HUF-OCT-2015-01
First Posted: December 4, 2015    Key Record Dates
Last Update Posted: August 17, 2016
Last Verified: August 2016
Additional relevant MeSH terms:
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Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants