Incidence of Ultrasonographically Detected Articular Damage in Initially Healthy Joints of Patients With Hemophilia A Receiving Prophylactic Treatment With Emicizumab. A Prospective Observational Study
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Measurement of Ultrasonographically Detected Articular Damage in Elbows, Knees, and Ankles
研究概览
简要总结
Introduction: Prophylaxis with emicizumab has substantially improved hemorrhagic control in hemophilia A. However, the longitudinal incidence of ultrasonographically detected articular damage in initially healthy joints remains insufficiently characterized.
Objective: To estimate the incidence of ultrasonographically detected articular damage in initially healthy joints among patients with hemophilia A receiving prophylaxis with emicizumab and to explore its association with relevant clinical variables.
Methods: A prospective, longitudinal, observational study will be conducted in approximately 70 patients with hemophilia A receiving emicizumab, with an estimated recruitment of approximately 270 initially healthy joints. The study is purely observational and does not involve evaluation of the investigational product nor modification of the therapeutic regimen; dosing, administration intervals, and all clinical decisions regarding emicizumab will be determined exclusively at the discretion of the treating hematologist. Assessments will be performed at baseline and at 12 and 24 months. The unit of analysis will be the joint, including elbows, knees, and ankles without ultrasonographic evidence of articular damage and without a history of clinically evident hemarthrosis at study entry.
The primary endpoint will be the occurrence of incident ultrasonographically detected articular damage, assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol. Secondary outcomes will include clinical joint health assessed by the Hemophilia Joint Health Score (HJHS), version 2.1; the frequency of joint hemarthroses measured by the annualized joint bleeding rate (AJBR); and habitual physical activity levels evaluated through age-specific validated questionnaires. Statistical analyses will account for intra-patient correlation among joints.
Expected Results: A low to moderate incidence of ultrasonographically detected articular damage in initially healthy joints is anticipated during follow-up, providing clinically relevant information regarding structural joint preservation in patients with hemophilia A receiving emicizumab prophylaxis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of hemophilia A;
- •Receiving prophylactic treatment with emicizumab (Hemlibra®) according to routine clinical practice;
- •Age ≥10 years at the time of study enrollment;
- •Absence of ultrasonographic joint damage in at least one of the evaluated joints (elbows, knees, or ankles), defined as HEAD-US = 0 at baseline assessment;
- •No documented history of clinically evident hemarthrosis in the corresponding joints from initiation of emicizumab prophylaxis to the study baseline evaluation;
- •Ability to understand and complete study procedures (interviews, questionnaires, and clinical assessments), in accordance with the participant's age; and
- •Provision of written informed consent; for minors, written informed consent from parents or legal guardians and assent from the minor participant, in accordance with applicable regulations.
排除标准
- •Presence of ultrasonographic joint damage (HEAD-US ≥1) in all evaluated joints at the baseline visit;
- •Documented history of clinically evident hemarthrosis in the joints under study;
- •Prior major orthopedic surgery or arthroplasty in the evaluated joints;
- •Presence of concomitant musculoskeletal pathology unrelated to hemophilia that could interfere with joint assessment (e.g., inflammatory arthritis, recent severe trauma);
- •Inability to complete the planned 24-month follow-up or to undergo study assessments;
- •Concurrent participation in another interventional study that could interfere with the joint health variables under evaluation; and
- •Any clinical or social condition that, in the investigator's judgment, could compromise participant safety or the validity of the study data.
研究组 & 干预措施
Observational group
Patients with hemophilia A receiving prophylactic treatment with emicizumab
干预措施: Hemophilia patients (Other)
结局指标
主要结局
Measurement of Ultrasonographically Detected Articular Damage in Elbows, Knees, and Ankles
时间窗: Baseline visit, at 12 months, and at 24 months.
Ultrasonographically detected articular damage will be assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol through standardized musculoskeletal ultrasound examination. This scoring system evaluates three structural domains per joint: synovial (hypertrophy and effusion), cartilage, and bone. Each joint is assigned an ordinal score ranging from 0 (no abnormalities) to a maximum of 8 points, derived from the combined assessment of the synovial, cartilaginous, and osseous domains. The HEAD-US protocol enables detection of subclinical joint damage and early structural changes, even in the absence of clinically evident hemarthrosis.Scree
次要结局
- Measurement of Clinical Joint Health in Knees, Ankles, and Elbows(Baseline visit, at 12 months, and at 24 months.)
- Measurement of Joint Hemorrhagic Phenotype(Baseline visit, at 12 months, and at 24 months.)
- Measurement of Physical Activity Level in patients under 18 years of age(Baseline visit, at 12 months, and at 24 months.)
- Measurement of Physical Activity Level in Adult Patients(Baseline visit, at 12 months, and at 24 months.)
- Measurement of Treatment Adherence(Baseline visit, at 12 months, and at 24 months.)
研究者
Rubén Cuesta-Barriuso
Principal Investigator
Investigación en Hemofilia y Fisioterapia