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.
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;
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);
Patients with hemophilia A receiving prophylactic treatment with emicizumab
Cohort
Prospective
Hemophilia patients
Other interventionA prospective, longitudinal, observational study will be conducted in patients with hemophilia A receiving prophylaxis with emicizumab, with a 24-month follow-up period. Three assessments will be performed: at baseline, 12 months, and 24 months.
Measurement of Ultrasonographically Detected Articular Damage in Elbows, Knees, and Ankles
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
Measurement of Clinical Joint Health in Knees, Ankles, and Elbows
Clinical joint health will be assessed using the Hemophilia Joint Health Score, version 2.1 (HJHS 2.1). This instrument evaluates eight items per joint: swelling (edema), duration of swelling, pain, muscle atrophy, crepitus, strength deficit, loss of range of motion, and joint deformity. Additionally, it includes a global gait assessment scored from 0 to 4. Each item is rated on an ordinal scale according to the instrument's predefined criteria, yielding a per-joint score ranging from 0 to 20 and a total score ranging from 0 to 124. Higher scores indicate worse clinical joint health.
Measurement of Joint Hemorrhagic Phenotype
This variable will be assessed using the Annualized Joint Bleeding Rate (AJBR), calculated as the number of hemarthroses occurring during the observation period divided by the total days of follow-up and multiplied by 365.25. The AJBR will be calculated both globally and on a per-joint basis, based on systematically recorded bleeding events obtained through structured clinical interviews.
Measurement of Physical Activity Level in patients under 18 years of age
This variable will be assessed using the Physical Activity Questionnaire for Adolescents (PAQ-A). The PAQ-A consists of nine items evaluating participation in various types of physical and sports activities; frequency of activity during physical education classes; activity during recess and leisure time; after-school activity; weekend activity; and overall level of habitual physical activity. Each item is scored on a 5-point Likert scale (1 to 5), and the final score corresponds to the mean of all items. Higher scores indicate a greater level of habitual physical activity.
Measurement of Physical Activity Level in Adult Patients
This variable will be assessed using the International Physical Activity Questionnaire - Long Form (IPAQ-LF). The IPAQ-LF captures physical activity across four domains: work-related physical activity, active transportation, domestic and household activities, and leisure-time physical activity. Within each domain, the time spent in vigorous-intensity activity, moderate-intensity activity, and walking is recorded, allowing for the calculation of total energy expenditure expressed in MET-minutes per week (MET-min/week).
Measurement of Age
This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years)
Measurement of Hemophilia Severity
This variable, used to describe the sample and control for potential confounding factors, will be measured as an ordinal variable (severe / moderate / mild).
Measurement of Inhibitor Status
This variable, used to describe the sample and control for potential confounding factors, will be measured as a dichotomous variable (yes / no)
Measurement of Duration of Emicizumab Prophylaxis
This variable, used to describe the sample and control for potential confounding factors, will be measured as a quantitative variable (in years).
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
