Efficacy of Intra-Articular Bevacizumab in Preventing Recurrent Hemarthrosis in Hemophilia Patients With Chronic Synovitis: A Pre- and Post-Design Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 4
- 主要终点
- Annualized Bleeding Rate (ABR) of the Target Joint
研究概览
简要总结
Hemophilia is an inherited bleeding disorder characterized by deficiency of clotting factors, leading to increased bleeding tendencies. The most common complications are joint bleeds (hemarthroses), which cause chronic changes in joints and ultimately disability. Recurrent hemarthroses often result from chronic synovitis in target joints of patients with hemophilia, a process driven by Vascular Endothelial Growth Factor (VEGF) mediated pathological angiogenesis. Intra-articular administration of Bevacizumab, a VEGF neutralizing monoclonal antibody, may block this process and reduce the frequency of recurrent joint bleeds. This study evaluates the efficacy and safety of intra-articular Bevacizumab for preventing recurrent hemarthrosis in patients with hemophilia and chronic synovitis.
详细描述
Hemophilia A is the most prevalent inherited bleeding disorder in Pakistan, accounting for approximately 69% of all hemophilia cases. A major complication is recurrent joint bleeding (hemarthrosis), which leads to chronic synovitis and progressive hemophilic arthropathy. This joint deterioration significantly impairs mobility and quality of life.
The underlying pathophysiology is driven by repeated hemarthroses, which cause increased local expression of Vascular Endothelial Growth Factor (VEGF). VEGF promotes abnormal angiogenesis and synovial proliferation, perpetuating a cycle of inflammation and bleeding, even when symptoms are not overt.
Bevacizumab is a recombinant humanized monoclonal antibody that specifically inhibits VEGF. Local intra-articular administration offers a targeted therapeutic approach to disrupt this pathogenic cycle directly at the site of pathology. By neutralizing VEGF, Bevacizumab may mitigate synovitis, reduce bleeding frequency, and slow progression of hemophilic arthropathy, while minimizing systemic exposure and associated adverse effects.
To investigate this therapeutic strategy, a two-year, open-label, single-arm clinical trial will be conducted at the Institute of Pathology and Diagnostic Medicine (IPDM), Khyber Medical University (KMU), and Hayatabad Medical Complex, Peshawar, Pakistan. A total of 25 participants with Hemophilia A and chronic synovitis in one or more target joints (knee, elbow, or ankle) will be enrolled.
All participants will receive intra-articular Bevacizumab injections following prophylactic factor replacement therapy to prevent procedure-related bleeding. The first four participants will receive 20 mg/0.8 mL per injection. If well tolerated without major toxicities, the remaining participants will receive 40 mg/1.6 mL per injection. Each injection will be administered into the target joint once every 28 days for a total of four doses.
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
盲法说明
This is an open-label study. No masking is used.
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of Hemophilia A.
- •Presence of one or more target joints (knee, elbow, ankle) with chronic synovitis and a history of >2 hemarthrosis episodes in the past 6 months.
- •Target joint World Federation of Hemophilia (WFH) joint score of 2-
- •Adequate hematological, renal, and liver function (as specified by protocol lab values).
- •Ability and willingness to provide informed consent and comply with the study protocol.
排除标准
- •HIV positive diagnosis.
- •Severely damaged joints or anatomical limitations preventing safe injection.
- •Contraindications to MRI.
- •Uncontrolled hypertension.
- •Recent major surgery/trauma (<28 days).
- •Serious non-healing wound, active cardiovascular disease, or other significant comorbidities that could increase risk or interfere with the study.
研究组 & 干预措施
Intra-articular Bevacizumab
All participants will receive intra-articular injections of Bevacizumab. The initial dose for the first four patients will be 20 mg/0.8 ml. If no major toxicities are observed, the dose will be escalated to 40 mg/1.6 ml for the remaining patients. Injections will be administered monthly for a duration of 4 months.
干预措施: Intra-articular Bevacizumab (Drug)
结局指标
主要结局
Annualized Bleeding Rate (ABR) of the Target Joint
时间窗: Baseline (3 months pre-treatment) compared to the 3-month period following the completion of the treatment protocol (i.e., 3 months after the 4th injection).
The efficacy of the intervention will be assessed by the change in the number of recurrent hemarthrosis episodes specifically in the treated target joint. The rate will be annualized from data collected over a 3-month period. Response will be categorized as: 'Excellent' (0 bleeds), 'Good' (75-99% reduction), 'Fair' (50-74% reduction), or 'Poor' (\<50% reduction).
Clinical Joint Health Score
时间窗: Baseline scores compared to scores at 1, 3, 6, and 12 months after initiation of therapy
Change in joint health and function as measured by the Hemophilia Joint Health Score (HJHS 2.1), a standardized physical examination tool that assesses pain, swelling, muscle atrophy, crepitus on motion, range of motion (flexion/extension loss), strength, and gait. Scale Range: 0 to 124 (higher scores indicate worse joint health and function). Interpretation: 0 = best outcome (no joint damage or impairment) 124 = worst outcome (severe joint involvement and functional limitation)
Synovial Hypertrophy
时间窗: Baseline MRI (before starting therapy) compared to MRI performed 6 months after completion of therapy.
Change in synovial membrane thickness in the target joint as assessed by MRI, scored according to the IPSG MRI scale for synovial hypertrophy (0-3; 0 = none, 3 = \>5 mm).
Joint Effusion/Hemarthrosis
时间窗: Baseline vs. 6 months after completion of therapy.
Change in effusion or hemarthrosis volume in the target joint, assessed using the IPSG MRI scale (0-3; 0 = none, 3 = severe joint distention).
Synovial Inflammation Composite (Soft Tissue Subtotal)
时间窗: Baseline vs. 6 months after completion of therapy.
Change in the combined soft tissue inflammation score, calculated as the sum of effusion/hemarthrosis, synovial hypertrophy, and hemosiderin deposition (range 0-9)..
次要结局
未报告次要终点