Intensive Replacement Treatment in Haemophilia Patients With Synovitis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- changes in synovitis
研究概览
简要总结
Background: Joint haemorrhage represents the most common type of bleeding episode in persons with hemophilia (PwH). In the absence of an adequate prophylaxis with Factor VIII (for hemophilia A) or FIX (for hemophilia B) concentrates up to 85% of patients with severe hemophilia develop a clinically overt joint disease. Screening of early signs of arthropathy is needed. Synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH.
Aim: To assess if an intensive factor VIII replacement treatment is able at reverting synovitis in PwH.
Methods: The present study is a randomized, open-label, cross-over study. Among patients referred to enrolling Haemophilia Centres, consecutive patients with severe (FVIII < 1%) or severe-moderate (FVIII < 2%) haemophilia A without inhibitors will be enrolled. The present study will be organized in 2 phases.
- Phase 1 (US screening): All patients will undergo an ultrasound examination of elbows, ankles and knees to define joint status and to identify presence/absence of synovitis according to the HEAD-US system.
- Phase 2 (Intervention): Patients with US evidence of synovitis will be randomly assigned at undergoing a PK assessment with my-PK-fit to start a prophylaxis with Adynovi® targeting a 12% FVIII through level (PROPEL-like arm) or to continue ongoing standard treatment (control arm). US examination of the six joints will be repeated monthly for six months and in case of onset of symptoms that might suggest an acute bleeding episode. After six months the two treatment arm will be switched in the frame of a cross-over approach and all PwH will be followed for other 6 months The primary outcome will be represented by changes in synovial status during the intensive factor VIII replacement treatment vs standard treatment.
详细描述
Joint haemorrhage represents the most common type of bleeding episode in persons with hemophilia (PwH) and recurrent hemarthrosis triggers chronic arthropathy, which is the most frequent chronic complication in hemophilia patients. In the absence of an adequate prophylaxis (age at start, regimen, duration, adherence) with Factor VIII (for hemophilia A) or FIX (for hemophilia B) concentrates, up to 85% of patients with severe hemophilia develop a clinically overt joint disease.
On the other hand, some recent data suggest that, despite adequate prophylaxis a not negligible percentage of PwH develop arthropathy.
Thus, an adequate screening of early signs of arthropathy is needed. On this hand, synovitis is widely considered as one of the parameters to be taken into account for the diagnosis and the surveillance of joint impairment in PwH. Synovitis represents a key feature, potentially related to under-treatment due to insufficient therapy regimens or to a limited compliance to treatment, to pharmacokinetics variability or to demanding daily/sport activities. Accordingly, there is a general agreement on the indication to consider the presence of synovitis as a marker of disease activity in PwH.
MATERIALS AND METHODS:
Among patients referred to enrolling Haemophilia Centres (to be defined), consecutive patients with severe (FVIII < 1%) or severe-moderate (FVIII < 2%) haemophilia A without inhibitors will be enrolled according to the above reported inclusion and exclusion criteria. For each subject, a trained staff will record demographic data including age, race, ethnicity, body mass index (BMI, kg/m2). Information from medical records will also include the number of bleeding episodes and the amount of factor concentrate used during the previous 12 months for regular prophylaxis and for breakthrough bleeding episodes treatment. The present study will be organized in 2 phases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male patients with > 12 years of age, with severe (FVIII < 1%) or severe-moderate (FVIII < 2%) haemophilia A without inhibitors, receiving a prophylactic treatment with FVIII.
- •Evidence at ultrasound evaluation of synovitis (grade 1-2 according to HEAD-US score)
- •Signed and dated informed consent form for data collection prior to enrolment.
排除标准
- •Patients with bleeding disorders other than haemophilia A
- •Patients with anti-FVIII inhibitor (any titer).
- •Patients receiving on-demand treatment with FVIII
- •Patients with liver cirrhosis
- •Any condition that compromises the patient's ability to perform study-related activities or that poses a clinical contraindication to study participation.
- •Patients unwilling or unable to follow the terms of the protocol.
研究组 & 干预措施
PROPEL-like arm
EHL-FVIII prophylaxis targeting a 12% FVIII through level based on PK assessment with WAPPS-Hemo
干预措施: EHL-FVIII (Drug)
Control arm
standard treatment with FVIII concentrate according to current guidelines
干预措施: FVIII concentrate (Drug)
结局指标
主要结局
changes in synovitis
时间窗: from baseline up to 6 months
The primary outcome of the present study is to assess if an intensive factor VIII replacement treatment is able at reverting synovitis in persons with haemophilia (PwH).
次要结局
未报告次要终点
研究者
Matteo Di Minno
Prof
Federico II University