Clinical validation of Factor VIII allo-antibody assays in patients with severe hemophilia A (PSTOL 15).

The correlation of factor VIII antibodies, measured with different assays, and factor VIII survival in patients with severe haemophilia A.

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON23098

Enrollment

150

Registered

2011-06-21

Start date

2008-12-04

Completion date

Unknown

Last updated

2024-06-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

severe haemophilia A patients, low titer assay, factor VIII antibodies, negative Bethesda assay, pharmacokinetic

Interventions

At inclusion by the haematologist blood will be taken for the assessment of hemoglobin concentration, haematocrit value and blood group. During the experimental part of the study, the patients will un

Eligibility

Inclusion criteria

Inclusion criteria: Inclusion criteria for patients with severe haemophilia A without inhibitors are: 1. Less than 1% factor VIII activity (severe clinical phenotype of haemophilia A); 2. No factor VIII infusion for minimally 72 hours; 3. Normal response to factor VIII during bleeding episodes; 4. Normal recovery (>1,5%/U/kg); 5. No recent change in bleeding pattern; 6. No history of an inhibitor. Inclusion criteria for patients with severe haemophilia A with or at high risk of having factor VIII inhibitors: 1. Less than 1% factor VIII activity (severe clinical phenotype of haemophilia A); 2. No factor VIII infusion for minimally 72 hours; 3. Diminished response to factor VIII compared to past performance: A. Or: Low recovery of factor VIII; B. Or: More frequent bleedings and/or a different bleeding pattern; C. Or: Higher need for FVIII substitution than before.

Exclusion criteria

Exclusion criteria: Exclusion criteria for patients with severe haemophilia A without inhibitors are: 1. Known allergy to plasma proteins; 2. Fever (higher than 38 °C); 3. Clinical indication of liver cirrhosis (echographic indication, enlarged spleen, enlarged liver, decreased platelet count); 4. Hepatitis C treated with interferon within 6 months prior to inclusion; 5. HIV positive; 6. Medication: A. NSAIDs (non-steroid anti-inflammatory drugs); B. Specific platelet inhibitors (aspirin, clopidogrel, RheoPro); C. Antimicrobial medication; D. Thyroid inhibitors; E. Selective serotonin re-uptake inhibitors. 7. Hb levels less than 8.0 mmol/l; 8. Platelet counts less than 50*109/ltr; 9. Difficile venous acces; 10. Change of factor VIII concentrate used during the last year. Exclusion criteria for patients with severe haemophilia A with inhibitors or suspected of having factor VIII inhibitors: 1. Known allergy to plasma proteins; 2. Fever (higher than 38 °C); 3. Clinical indication of liver cirrhosis (echographic indication, enlarged spleen, enlarged liver, decreased platelet count); 4. Hepatitis C treated with interferon within 6 months prior to inclusion; 5. HIV positive; 6. Medication: A. NSAIDs (non-steroid anti-inflammatory drugs); B. Specific platelet inhibitors (aspirin, clopidogrel, RheoPro); C. Antimicrobial medication; D. Thyroid inhibitors; E. Selective serotonin re-uptake inhibitors. 7. Hb levels less than 8.0 mmol/l; 8. Platelet counts less than 50*109/ltr; 9. Difficile venous acces.

Design outcomes

Primary

Measure	Time frame
1. To study the correlation between the antibody levels measured with the different assays and the pharmaco kinetic parameters; 2. To calculate the sensitivity, specificity, negative and positive predictive value of the different assays with respect to the pharmaco kinetics of factor VIII.	—

Secondary

Measure	Time frame
1. Correlation of FVIII pharmaco kinetic parameters and inhibitor levels with von Willebrand factor. The von Willebrand factor may influence pharmacokinetic parameters of factor VIII as von Willebrand Factor (including ABO serology) is the chaperone molecule of factor VIII (Ref 13,14). Therefore it may also affect antibody levels; 2. Correlation of FVIII pharmaco kinetic parameters and inhibitor levels with total and transformed á2-macroglobulin. Factor VIII and á2-macroglobulin share one receptor for clearing the proteins from circulation, the lipoprotein receptor-related protein (LRP). Therefore, á2-macroglobulin levels may influence the pharmacokinetic parameters of factor VIII, factor VIII antibodies as well as the correlation between both in humans as it does affect factor VIII kinetics in mice (ref 15,16,17).	—

Measure

Time frame

1. Correlation of FVIII pharmaco kinetic parameters and inhibitor levels with von Willebrand factor. The von Willebrand factor may influence pharmacokinetic parameters of factor VIII as von Willebrand Factor (including ABO serology) is the chaperone molecule of factor VIII (Ref 13,14). Therefore it may also affect antibody levels; 2. Correlation of FVIII pharmaco kinetic parameters and inhibitor levels with total and transformed á2-macroglobulin. Factor VIII and á2-macroglobulin share one receptor for clearing the proteins from circulation, the lipoprotein receptor-related protein (LRP). Therefore, á2-macroglobulin levels may influence the pharmacokinetic parameters of factor VIII, factor VIII antibodies as well as the correlation between both in humans as it does affect factor VIII kinetics in mice (ref 15,16,17).

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Contacts

Public ContactW.L. Heerde, van

Radboud University Nijmegen Medical Centre Depart of Laboratory Medicine LH 441 PObox 9101

w.vanheerde@labgk.umcn.nl

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)