Treatment of thromBocytopenia With EltRombopag or Intravenous Immune Globulin (IVIG) Before and DurING Invasive Procedures in Patients With Immune ThrombocytoPenia- BRIDGING ITP Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 74
- 试验地点
- 10
- 主要终点
- Achievement of a platelet count level that is above the platelet count threshold for surgery preoperatively and that is maintained above the threshold during the post-hemostasis period without the use of rescue treatment
研究概览
简要总结
This is a study to investigate if eltrombopag can be used instead of Intravenous Immune Globulin (IVIG) in patients with ITP, to adequately raise their platelet count when they undergo minor or major surgery. Eltrombopag is a daily, oral pill approved for treatment of ITP. IVIG is a blood product frequently used to treat ITP. Patients with ITP who need surgery have to get treatment to increase their platelet count. IVIG is commonly used for this purpose but eltrombopag may be more effective and convenient for patients.
详细描述
Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease characterized by the presence of platelet autoantibodies, low platelet counts and an increased risk of bleeding. TPO receptor agonists which stimulate platelet production have been shown to be remarkably effective in ITP. Their use as a short-term means of elevating platelet counts in preparation for surgical procedures has not yet been adequately evaluated.
Many patients with moderate to severe ITP (platelet count less than 50 x 10exp9/L) have stable platelet counts and do not bleed; however, when surgeries or invasive procedures become necessary, additional treatment is often required to increase the platelet count to achieve adequate hemostasis. Although specific guidelines for surgical platelet count thresholds in ITP are lacking, platelet transfusion guidelines recommend a platelet count of 50 - 100 x10exp9/L for the vast majority of surgical procedure; 50x10exp9/L is a typical threshold for minor surgeries like tooth extractions and endoscopies; and 100x10exp9/L is used for major surgery like cardiac surgery or neurosurgery.
Commonly, intravenous immunoglobulin (IVIG) is used to rapidly increase platelet counts in ITP patients before an invasive procedure. IVIG is associated with a transient platelet count response in approximately 80% of patients, which occurs within 2 - 4 days. In most patients, platelet counts remain elevated for approximately 4 weeks, allowing enough time to complete the procedure and for adequate post-operative hemostasis. However, IVIG is a resource-intensive and expensive blood product associated with frequent side effects.
Eltrombopag is a small molecule, non-peptide thrombopoietin (TPO) receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. TPO receptor agonists are an effective new class of medications that are non-immunogenic agonists of the TPO receptor (c-Mpl) and work by increasing platelet production in ITP patients. In randomized controlled trials, eltrombopag maintenance therapy has been shown to raise the platelet count in 60 - 80% of ITP patients and platelet counts generally remain elevated as long as the drug is continued. Time to response is 1 - 2 weeks with minimal need for dose titration. Side effects of eltrombopag observed in clinical studies included elevation of liver enzymes (approximately 10% of patients). The risk of thrombosis and bone marrow reticulin formation remain uncertain.
The investigators propose a randomized controlled trial (RCT) involving 74 patients (across approximately 8 centers) in Canada. This study will evaluate the efficacy and safety of eltrombopag bridging therapy compared with IVIG bridging therapy in adult patients with ITP who require surgery. This study will also evaluate bleeding, adverse events and patient-reported treatment satisfaction using the Treatment Satisfaction Questionnaire for Medication (TSQM). Patients will be stratified according to centre and surgery type (major vs. minor).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary or secondary ITP;
- •Platelet count below surgical platelet count threshold (50 x10^9/L for minor surgery; 100 x 10^9/L for major surgery);
- •18 years of age or older;
- •On stable doses of concomitant ITP medications (i.e the dose administered has not changed) or no ITP medication for at least 2 weeks;
- •At least 3-weeks lead time available between randomization and scheduled surgery;
- •IVIG and Eltrombopag are acceptable ITP treatment options for this patient;
- •Able to provide informed consent.
排除标准
- •Pregnancy or breastfeeding;
- •Treatment with IVIG within the last 2 weeks;
- •Treatment with a thrombopoietin receptor agonist (eltrombopag or romiplostim) within the last 4 weeks;
- •AST, ALT above 2X upper limit of normal;
- •Bilirubin above 1.5X upper limit of normal in the absence of clinically benign liver disorder (eg. Gilberts syndrome);
- •Deep vein thrombosis, myocardial infarction, thrombotic stroke or arterial thrombosis in the last 12 months;
- •History of bone marrow reticulin or fibrosis;
- •Known liver cirrhosis;
- •Active malignancy (defined as requiring treatment or palliation within the last 6 months);
- •Any additional laboratory test result, health related illness or other diagnosis which, in the opinion of the treating physician, may put the subject's health or safety at risk.
研究组 & 干预措施
Eltrombopag
Eltrombopag is a small molecule, non-peptide thrombopoietin (TPO) receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. TPO receptor agonists are an effective new class of medications that are non-immunogenic agonists of the TPO receptor (c-Mpl) and work by increasing platelet production in ITP patients.
干预措施: Eltrombopag (Drug)
IVIG infusion
Intravenous immunoglobulin (IVIG) is used to rapidly increase platelet counts in ITP patients. IVIG is associated with a transient platelet count response in approximately 80% of patients, which occurs within 2 - 4 days. It is commonly used to improve platelet count numbers prior to surgery for patients with ITP.
干预措施: IVIG infusion (Drug)
结局指标
主要结局
Achievement of a platelet count level that is above the platelet count threshold for surgery preoperatively and that is maintained above the threshold during the post-hemostasis period without the use of rescue treatment
时间窗: For a the period of time from the final pre-operative visit until 7 days after surgical hemostasis is achieved
Threshold is a platelet count of 50 x 10\^9/L for minor surgery and 100 x 10\^9/L for major surgery.
次要结局
- Bleeding(During treatment and follow up (on average, 8 weeks from starting treatment))
- Adverse Events(During treatment and follow up (on average, 8 weeks from starting treatment))
- Time to treatment failure(During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved)
- Surgical delays or cancellations(Measured at time of planned surgery)
- Thrombocytosis(During treatment and follow up (on average, 8 weeks from starting treatment))
- Blood product transfusions(During treatment and follow up (on average, 8 weeks from starting treatment))
- Rescue treatment(During the period from the final pre-operative visit until 7 days after surgical hemostasis is achieved)
- Hospitalizations(During treatment and follow up (on average, 8 weeks from starting treatment))
- Thrombosis(During treatment and follow up (on average, 8 weeks from starting treatment))
- Platelet count change over time(During treatment and follow up (on average, 8 weeks from starting treatment))
- Patient satisfaction with treatment(Immediately before surgery (final pre-op visit) and 7 days (+/- 2 days) after surgical hemostasis is achieved)
研究者
Donald Arnold
Principal Investigator
McMaster University