Clinical Outcomes of Low Dose Pharmacokinetic-guided Extended Half-life FVIII Concentrates Versus Low Dose Standard Prophylaxis in Thai Severe Haemophilia A Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Changing bleeding rate after switch from SHL to EHL with PK-guided dosing
研究概览
简要总结
Individualised pharmacokinetic (PK)-guided dosing of extended half-life (EHL) FVIII concentrates prophylaxis may reduce hemophilia A bleeding events than previous prophylactic regimen.
Methods A single-centre prospective cohort study, the investigators recruited consecutive eligible patients aged 5-25 years with clinically severe haemophilia A (FVIII:C ≤3%), no inhibitor, on low-dose weight-based prophylaxis at King Chulalongkorn Memorial Hospital (KCMH) from July 2021 to February 2022.
All of patients with clinically severe haemophilia A received low dose weight-based standard half-life FVIII concentrates replacement prophylaxis for ≥ 1 year prior to enrolment in the study.
The data of annual bleeding rate (ABR), annual joint bleeding rate (AJBR), annual FVIII use (prophylactic and breakthrough bleeding dosing) in the last 6 months before the study and number of target joints were collected at the beginning of the study.
Baseline variables, including age and weight, were recorded before performing the analyses using online medical device (www.mypkfit.com).
Wash-out period for 72 hours, each participant subsequently received a dose of 20 IU/kg FVIII by intravenous injection. Blood samples were collected and the concentration of FVIII was measured two times at 3 h and 48 h or 72 h after injection by one-stage technique. Desired FVIII trough levels were selected in this study as 1%. Individually proper regimen were selected by discussion with patients and families.
All of participant individually underwent dose calculation of EHL factor VIII concentrates and received low dose PK-guided regimen (10-20u/kg, 2-3times/week) with EHL FVIII concentrates for 6 months. If breakthrough bleeding occurs, FVIII concentrates 500 U intravenous injection immediately.
ABR, AJBR, HJHS and annual FVIII concentrates use were again prospectively recorded during intervention period after PK adjustment for 6 months.
Primary objectives To compare clinical outcomes including annual bleeding rate (ABR), annual joint bleeding rate (AJBR) and Haemophilia joint health score (HJHS) before and after switching from standard half-life (SHL) to Extended half-life (EHL) factor VIII concentrates with adjusted dosing by PK-guided program (MyPKFiT®) in severe haemophilia A patients Secondary objectives To compare factor VIII concentrates consumption before and after using PK-guided program (MyPKFiT®) adjusting dose of factor VIII infusion in severe HA patients.
详细描述
Clinical Outcomes of Low Dose Pharmacokinetic-guided Extended Half-life Versus Low Dose Standard Half-life FVIII Concentrates Prophylaxis in Thai Severe Haemophilia A Patients
Haemophilia A (HA) is a X-linked inherited bleeding disorders caused by a deficiency in the clotting factor VIII (FVIII). The degree of deficiency was determined by a patient's FVIII level and clinical bleeding phenotype. Clinically severe haemophilia A (FVIII < 1 IU/dL) typically present with recurrent joint and muscle bleeds. They may also experience spontaneous and potentially fatal bleeds in any tissue.
The standard of care for all patients with severe haemophilia A is regular factor replacement prophylaxis with clotting factor concentrates or other homeostasis products to maintain homeostasis for preventing bleeding, especially joint haemorrhages, which lead to arthropathy and disability. People with haemophilia A initiated on early prophylaxis (i.e., primary or secondary prophylaxis) have shown the best long-term outcomes. Therefore, the use of prophylaxis is always recommended over episodic therapy that no longer be a long-term treatment option.
The aim of prophylaxis has been to convert a person with severe haemophilia (baseline FVIII <1 IU/dL) to a bleeding phenotype typical of moderate or mild haemophilia who seldom experienced spontaneous bleeding and had much better preservation of joint function by maintaining factor levels above 1 IU/dL (1%) at all times. However, there has been increasing recognition and evidence that factor trough levels of 1-3 IU/dL (1%-3%) are insufficient to totally prevent bleeds in all people with haemophilia and allow occasional clinical and subclinical bleeds. And when baseline FVIII:C levels are above 15 IU/dL (15%), spontaneous bleeding is uncommon, traumatic bleeding during high activity is few.
The World Federation of Haemophilia (WFH) strongly recommends that prophylaxis should be individualised, taking into consideration patient bleeding phenotype, joint status, level of physical activity, individual pharmacokinetics, compliance, and patient self-assessment and preference in severe haemophilia patients. If patients continue to experience bleeds, their prophylaxis regimen should be escalated (in dose/frequency or both) to prevent bleeding. In countries with significant healthcare constraints and for patients with limited access to clotting factor concentrates, less intensive prophylaxis should be used over episodic therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open label, all participants received individual low-dose PK-guided extended FVIII concentrates prophylaxis.
入排标准
- 年龄范围
- 5 Years 至 25 Years（Child, Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •severe or moderate with clinically HA with a baseline FVIII level of ≤3 IU/dL
- •age 5-25 years
- •> 50 exposure days (EDs) without inhibitor
- •close proximity to the comprehensive care center at KCMH
- •compliant to treatment
- •use of the pre-study prophylaxis regimen for ≥ 1 year prior to enrolment in the study.
排除标准
- •history of FVIII inhibitor (titer > 0.6 Bethesda units [BU]) and detectable FVIII inhibitor at screening (titer > 0.6 BU)
- •planned major surgery, and (3) concomitant serious conditions including symptomatic human immunodeficiency virus (HIV) infection, juvenile rheumatoid arthritis, metabolic bone disease, or other conditions known to mimic or cause joint diseases.
研究组 & 干预措施
Severe haemophilia A patients with weight-based prophylaxis
Severe haemophilia A patients with low-dose standard half-life concentrates weight-based prophylaxis
干预措施: standard half-life FVIII concentrates with weight-based dosing (Drug)
Severe haemophilia A patients with low dose extended half-life PK-guided prophylaxis
Severe haemophilia A patients with low-dose extended half-life concentrates PK-guided prophylaxis
干预措施: Extended half-life FVIII concentrates with PK-guided dosing (Drug)
结局指标
主要结局
Changing bleeding rate after switch from SHL to EHL with PK-guided dosing
时间窗: 6 months
To compare bleeding events including annual bleeding rate (ABR) in numbers per year, and annual joint bleeding rate (AJBR) in numbers per year before and after switching from standard half-life (SHL) to Extended half-life (EHL) factor VIII concentrates with adjusted dosing by PK-guided program (MyPKFiT®) in severe haemophilia A patients The higher scores mean the worse outcome.
Changing the joints health outcomes after switch from SHL to EHL with PK-guided dosing
时间窗: 6 months
Haemophilia joint health score (HJHS) version 2.1 before and after switching from standard half-life (SHL) to Extended half-life (EHL) factor VIII concentrates with adjusted dosing by PK-guided program (MyPKFiT®) in severe haemophilia A patients Haemophilia joint health score (HJHS) assessed by physical examination of joint health including length of motion, swelling, pain and pattern of gait. The higher scores mean the worse outcome. The minimal score is zero and the maximal score is 178.
次要结局
- Changing factor consumption after using PK-guided program(6 months)