StOP Haemophilia A Study
Research type
Research Study
Full title
Strategies for Optimising Prophylaxis – Clinical Utility and Accuracy of Model Predicted Factor VIII half-life and Trough Levels Compared to Current Recommended Prophylaxis Monitoring Strategies in Routine Clinical Practice in Adult Haemophilia A – StOP Haem A Study
IRAS ID
191148
Contact name
Pratima Chowdary
Contact email
Sponsor organisation
Royal Free London NHS Foundation Trust
Duration of Study in the UK
1 years, 6 months, 1 days
Research summary
Haemophilia A is an X-linked inherited bleeding disorder caused by deficiency of coagulation protein factor VIII (FVIII). Patients experience spontaneous and traumatic bleeding principally affecting the joints with resultant disability. Current standard of care is replacement therapy with FVIII concentrate administered on two to three occasions a week, i.e. prophylaxis, with the aim of maintaining levels above 1% between injections to prevent spontaneous bleeds. In routine clinical practice the dose and frequency of infusion is based on body weight. The effectiveness of prophylaxis is assessed by reviewing the number of joint bleeds over a period of 6 to 12 months and regular assessment of their joint health. Currently two monitoring strategies are recommended by United Kingdom Haemophilia Doctors Organisation (UKHCDO) guidelines on adult prophylactic regimens for assessing the adequacy of dose and frequency of infusions. The first strategy is the gold standard recommended by UKHCDO. This include is a full pharmacokinetic (PK) study with sampling over a 48 to 72 hr time period. PK is the study of how body handles the drug and following a FVIII infusion, levels rise to normal range and over a period of time decrease back to low levels. Following a PK study it is possible to calculate the half-life of the drug and measure the levels of factor VIII at nadir / trough and prescribe treatment regimens that are more scientific. The basis for the recommendation is the presence of considerable interindividual variability in the half-life of factor VIII, with values ranging between 6 and 23 hrs. UKHCDO guidelines suggest that at a minimum, trough or nadir levels should be monitored where samples are ideally taken before the next injection (measured trough level).
Trough levels (i.e. lowest level that a medicine is present in the body) can be difficult to measure and methods that predict half-life and trough levels through PK software packages have been suggested. Whilst these methods have been attempted in clinical trials, they have not been used in routine clinical care. Further, we do now know the accuracy of the predicted values, namely the difference between measured and predicted levels.
A major aim of this study is to understand if the values predicted by the PK software (predicted half-life and trough) are as good as measuring the real thing (calculated half-life and measured trough). A secondary aim is to understand if the time and effort required for refining the monitoring of prophylaxis treatment, justifies the additional time, effort and resource.REC name
London - Hampstead Research Ethics Committee
REC reference
15/LO/1868
Date of REC Opinion
19 Nov 2015
REC opinion
Favourable Opinion