Guided Discontinuation Versus Maintenance Treatment of Sirolimus in Pediatric Patients With Kaposiform Hemangioendothelioma: a Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Remission of KHE and no use of sirolimus at one year follow-up.
研究概览
简要总结
This randomized controlled trial aims to compare guided discontinuation with maintenance treatment of sirolimus in pediatric patients with KHE.
详细描述
Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor that occurs in infants and children. KHE is characterized by sheets of spindle cells with an infiltrative pattern in the dermis, subcutaneous fat, and muscle. It is locally aggressive and can cause Kasabach-Merritt phenomenon, a serious life-threatening coagulopathy characterized by profound thrombocytopenia and hypofibrinogenemia. Sirolimus, one of the mTOR inhibitors, has become a new and very effective treatment, which is especially reliable for KHE with KMP and has acceptable side effects. However, there is yet no strong evidence on the best practice of treatment length of sirolimus. This randomized controlled trial aims to compare guided discontinuation with maintenance treatment in pediatric patients with KHE in order to provide a basis for the optimal treatment duration of sirolimus, as well as the clinical characteristics of pediatric patients who can safely reduce the dose till withdrawal.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Only the outcome assessors are blinded, neither clinicians nor patients, because they should be attentive of the risk of relapse in the discontinuation group. Also, it seems unethical if researchers were not to discover the group of patients in the maintenance group who can discontinue sirolimus without relapsing. Clinicians should be given the possibility to adjust dose and ensure the benefits of patients. Therefore, this trial only includes assessors blinding.
入排标准
- 年龄范围
- — 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant diagnosed with KHE with or without KMP
- •Participant age 0-12 years
- •Participant with detailed medical records of the disease at the time of screening
- •Participant with at least two years of remission of KHE and no previous toxicity or adverse events
- •Participant with normal liver and kidney function
- •Participant with signed and dated informed consent from the guardian(s)
排除标准
- •Participant with other hematological diseases
- •Participant with other solid tumor
- •Participant with general disease such as hypertension, diabetes, adrenal insufficiency, neurological diseases, liver and kidney dysfunction, and cardiopulmonary insufficiency.
- •Participant with infectious diseases
- •Unwilling participant
研究组 & 干预措施
Maintenance treatment group
After at least 2 years of remission of KHE, the participant receives sirolimus as usual. The serum concentration is supposed to be 5-7 ng/ml. If the effect or side effects of sirolimus require discontinuation, it is allowed to modify intervention, and if so, the patient stays in the maintenance group.
干预措施: Sirolimus (Drug)
Guided discontinuation group
After at least 2 years of remission of KHE, the discontinuation measurement should be guided by the clinician with the following principles:
- 10% monthly reduction of the previous dose at most.
- At least 5 half-lives between each reduction (2 weeks).
- Blood concentration should be monitored monthly. Adjustment can be suggested according to the linear relationship between the dose and the blood concentration.
- At least 6 months for the duration of guided discontinuation.
- Regular assessments and evaluations should be done.
If the condition relapses or worsens during this process, dose of sirolimus should be adjusted to the previously effective dose. After a 3-month stabilization phase, 5% monthly reduction of the previous dose could be considered.
干预措施: Sirolimus (Drug)
结局指标
主要结局
Remission of KHE and no use of sirolimus at one year follow-up.
时间窗: From admission to follow-up one year
The primary outcome is a binary variable. The primary outcome measure will be analyzed with binary logistic regression to estimate the odds ratio between the two groups.
次要结局
- Tumor volume(From admission to follow-up one year)
- Complaints(From admission to follow-up one year)
- Platelet count(From admission to follow-up one year)
- Remission of KHE and the dose of sirolimus at one year follow-up(From admission to follow-up one year)
- Relapse of KHE and the dose of sirolimus at one year follow-up(From admission to follow-up one year)
- Fibrinogen level(From admission to follow-up one year)
- Side effects of sirolimus(From admission to follow-up one year)