Efficacy and Cost Effectiveness of Standard Versus Pharmacokinetic Dosing During Factor VIII Prophylaxis in Adult Patients With Severe Haemophilia A
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- The number of clinically significant bleeds in patients taking routine prophylaxis compared to prophylaxis dosed according to individual pharmacokinetics
研究概览
简要总结
Patients with severe Haemophilia A need prophylactic factor VIII to reduce their risk of joint and soft tissue bleeds and to prevent or reduce joint damage. It is common practice to give enough factor VIII to maintain the trough level above 1% of normal and this has been supported in retrospective studies.
The amount of factor VIII required to maintain this trough level varies markedly between patients because their factor VIII half lives are different. This study will assess the role of regular pharmacokinetic (PK)monitoring and dose adjusted factor VIII to establish whether this is a more cost effective way of giving treatment and whether it is feasible in routine clinical practice. Patients will be treated for 6 months with their standard factor VIII regimen and followed up to establish their bleed frequency. They will then receive pharmacokinetic adjusted factor VIII to maintain a trough above 1.5% for a year and their bleed rate compared to standard treatment. If they have increased break through bleeds their factor VIII will be increased to maintain a trough of 3%.
详细描述
Study procedures
Recruitment and Consent Patients with severe Haemophilia A who are taking any regular prophylactic regimen with infusions of factor VIII at least 3 times a week and do not have a target joint will be eligible. Initial approach will be made by the Principal Investigator at the patients next scheduled review appointment.
Phase 1: Study enrolment Participants will be allocated a unique patient number upon enrolment into the study.
The following will be recorded at study enrolment:
- Date of birth
- Height and weight
- Baseline factor VIII based on historical data from the patient record
- History of a factor VIII inhibitor
- Information on the number and site of haemarthroses and soft tissue bleeds and total amount of factor VIII used in the preceding 12 months will be recorded, if known
- Quality of life assessment by Utility-EQ5D
- Joint assessment by Haemophilia Joint Health Score (HJHS)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Severe haemophilia A (baseline factor VIII < 1IU/dL)
- •Age 18 years and above
- •Patients taking any regular prophylactic regimen (defined as regular factor VIII infusions, at least 3 times a week, with the aim minimising haemarthroses and other clinically significant bleeds).
- •Low titre inhibitors, past history of an inhibitor, abnormal liver function, drugs that interfere with haemostasis and low CD4 counts are allowed.
排除标准
- •Presence of a target joint on prophylaxis (defined as 3 bleeds into one joint, during a 6 month period,during the last year).
- •The occurrence of more than 3 haemarthroses in the last year which required more than 2 infusions to resolve
研究组 & 干预措施
Pharmacokinetic based factor VIII dosage
Patient's routine prophylactic factor VIII concentrate infusion will be given in the morning and the exact time (hours and minutes) and dose recorded. There is no wash out so the date, time and dose of the previous 2 prophylactic doses must be accurately known. Samples will be collected that afternoon, the following morning and the following afternoon. Samples can be taken at any convenient time but the exact time must be recorded. Factor VIII levels will be measured and this pharmacokinetic data will be used to calculate the dose of factor VIII (to be infused on alternate days) required to maintain a predicted factor VIII ≥1.5 IU/dL at all times(this will be rounded up to the nearest full 250 IU vial)
干预措施: Pharmacokinetic based dosage change (Drug)
结局指标
主要结局
The number of clinically significant bleeds in patients taking routine prophylaxis compared to prophylaxis dosed according to individual pharmacokinetics
时间窗: 18 months
Factor VIII dosage tailored treatment based on pharmacokinetics
次要结局
- Compare the factor VIII usage between the two regimens(18 months)
- Compare the total number of all soft tissue bleeds between the two regimens(18 months)
- Compare the total number of all haemarthroses between the two regimens(18 months)
- Compare the quality of life (EQ5D) between the two regimens(18 months)
- Compare the patients' joint status between the two regimens using the HJHS score.(18 months)