Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Nirmish Shah
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Change in Pain as Measured by Visual Analog Scale (VAS)
研究概览
简要总结
In patients with SCD, the use of low dose anticoagulation as an outpatient may lead to a significant decrease in morbidity and as a result, decrease healthcare utilization and costs. This study attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
详细描述
There is not only significant morbidity associated with patients with SCD, but also costs associated with the numerous hospitalizations. Small studies have been unable to show clear benefit of the use of low dose anticoagulation in SCD due to limited sample size or the inclusion of very specific populations. However, studies have shown a decrease in the level of elevated prothrombotic markers with anticoagulation, and one study using full dose anticoagulation in patients with a generally milder form of SCD (with high protective hemoglobin) showed more rapid decrease in clinical pain with use of anticoagulation, suggesting a possible benefit of such therapy. Due to the paucity of data to support therapeutic dose LMWH in the more severe forms of SCD seen in the United States, we have chosen prophylactic dose anticoagulation. This study proposal attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.
The development of novel anticoagulants such as oral direct factor Xa (FXa) inhibitors allows the realistic use of daily prophylactic dosing as an outpatient. Past studies as detailed earlier have been limited by attempts to use subcutaneous injections or frequent, close monitoring for acenocoumarol treatment, both which are not ideal for chronic daily use. Furthermore, the use of global assays such calibrated automated thrombography (CAT) have shown further details about thrombin generation in a population which is hypercoagulable at baseline.
This is a double blind, parallel group, placebo controlled feasibility study with an enrollment target of 25 patients (12 per arm). All subjects that meet inclusion criteria as an outpatient, following a 1 month observation, will be randomized to receive an oral prophylactic dose factor Xa inhibitor (Apixaban 2.5mg po bid) or placebo for 6 months. Subjects will return for a 30 day (+/- 5 days) follow-up visit after the End of Treatment (EOT) visit. Initial randomization will occur by computerized randomization technique by the investigational drug services (IDS) at Duke University Medical Center.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •documented HgbSS, SC or HgbS-beta0 thalassemia,
- •age ≥18 years old and ≤80,
- •seen in outpatient clinic ≥2 times in past year
- •seen for an acute care visit (hospitalization, emergency department, or day hospital visit) for pain >2 times in the past year.
排除标准
- •Hospitalization or day hospital visit for pain crisis within the past 2 weeks
- •Patients with ≥10 acute care visits within the past year will be excluded
- •Creatinine >3.0 mg/dL
- •creatinine ≥1.5 mg/dL AND weight ≤60 kg
- •chronic use of antiplatelet or anticoagulation medication
- •Patients with known vasculopathy or Moya-Moya
- •platelet count <100 X 109/L
- •AST or ALT >3 times normal
- •chronic red blood cell transfusions (scheduled transfusions)
- •packed red blood cell transfusion within the past 2 months
- •Use of CYP3A4 and P-gp inhibitor medications
研究组 & 干预措施
Apixaban
Active drug Apixaban 2.5mg taken by mouth twice a day
干预措施: Apixaban (Drug)
Placebo
Sugar pills that look like Apixaban that will be taken by mouth twice a day
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Pain as Measured by Visual Analog Scale (VAS)
时间窗: Month 1 to Month 8
The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other.
次要结局
- Daily Pain Scores While Hospitalized as Measured by VAS(up to 8 months)
- Change in Thrombin Generation Using D-dimer Measurement as a Surrogate(Enrollment to 2 months)
- Number of Hospitalizations During Treatment(up to 8 months)