Efficacy and Safety of Sirolimus in the Treatment of the Complicated Vascular Anomalies
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Volumetric changes in complicated vascular anomalies to sirolimus
研究概览
简要总结
To evaluate the safety and efficacy of Sirolimus in complicated vascular anomalies in Chinese children
详细描述
Vascular anomalies are composed of vascular tumors and vascular malformations. The prognosis of vascular anomalies is significantly variable. Most of them had a benign course. However, complicated vascular anomalies can lead to disfigurement, organ disfunction and life-threatening with significant morbidity and mortality. Traditional treatments, including steroids, vincristine, cyclophosphamide and surgery, had limited response to complicated vascular anomalies. In the past few years, the inhibitor of the mammalian target of rapamycin (mTOR) signaling pathway-sirolimus has emerged as a treatment for severe vascular anomalies. Besides, preclinical studies also showed that the Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mTOR pathway play an important role in the development of vascular tumors and vascular malformations. However, the exact efficacious rate and complications of sirolimus are still unknow in china because of the lack of large scale of prospective studies. Therefore, it's important to perform this prospective study to determine the safety and efficacy of sirolimus in the treatment of Chinese children with complicated vascular anomalies, and this study will also make contributions to the diagnoses and treatments of vascular anomalies.
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
入排标准
- 年龄范围
- 0 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients included in the present research must be diagnosed with one of the following vascular anomalies:
- •Kaposiform Hemangioendotheliomas without Kasabach-Merritt Phenomenon
- •Tufted Angioma without Kasabach-Merritt Phenomenon
- •Capillary Malformations
- •Lymphatic Malformations
- •Venous Malformations
- •Capillary-Venous Malformation (CVM)
- •Capillary-Lymphatic Malformation (CLM)
- •Lymphatic-Venous Malformation (LVM)
- •Capillary-Lymphatic-Venous Malformation (CLVM)
- •Multifocal Lymphangiomatosis and Thrombocytopenia (MLT)
- •Patients must be 0 - 18 years of age at the time of study entry.
- •Without functional impairment requiring treatment of corticosteroid.
- •Organ function requirements:
- •Adequate liver function Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)for age, and alanine transaminase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 x upper limit normal (ULN) for age.
- •Adequate renal function 0-5 years of age maximum serum creatinine (mg/dL) of 0.8 6-10 years of age maximum serum creatinine (mg/dL) of 1.0 11-15 years of age maximum serum creatinine (mg/dL) of 1.2 16-18 years of age maximum serum creatinine (mg/dL) of 1.5
- •Adequate bone marrow function:
- •Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 to the ninth/Liter
- •Consent of parents (or the person having parental authority in families): Signed and dated written informed consent.
排除标准
- •Allergy to sirolimus or other rapamycin analogues.
- •Allergy to sirolimus or other rapamycin analogues.
- •Any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of randomization.
- •Patients must not be known to be Human Immunodeficiency Virus positive or known immunodeficiency. Testing is not required unless a condition is suspected.
- •Other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration).
- •Impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus.
- •Patients who have a history of malignancy.
- •Patients with an inability to participate or to follow the study treatment and assessment plan.
- •Patients who have a history of treatment with sirolimus or other mTOR inhibitor.
研究组 & 干预措施
Sirolimus
干预措施: Sirolimus (Drug)
结局指标
主要结局
Volumetric changes in complicated vascular anomalies to sirolimus
时间窗: Baseline, 6, and 12 months
Response to sirolimus treatment was measured by volumetric magnetic resonance imaging (MRI) analyses, which were performed at baseline and 6 and 12 months after treatment and were independently assessed by 2 radiologists. Changes in size of vascular anomalies were classified as further growth (increase of ≥10%), no change (\<10% increase and \<10% decrease), partial involution (decrease of ≥10% and \<75%), nearly complete involution (decrease of ≥75% and \<100%), or complete involution (100%). Photographs of the complicated vascular anomalies were taken at months 0, 3, 6 and 12 by a medical photographer. Complete/nearly complete resolution of the vascular anomalies at month 12 compared to baseline based on the intra-patient blinded centralized independent qualitative assessments of month 12 MRI.
The changes in the patient's symptoms and/or complications.
时间窗: Baseline, 3, 6, and 12 months
次要结局
- Quality of Life in patients by the Pediatric Quality of Life Inventory TM (PedsQLTM) 4.0 Generic Core Scales.(Baseline, 6, 12 months)
- Measuring the impact of vascular anomalies on family functioning by PedsQLTM 4.0 Family Impact Module (FIM).(Baseline, 6, 12 months)
- Frequency of adverse events as assessed by CTCAE v4.0(Baseline, 3, 6, 12 months)
- Changes in plasma levels fibrinogen and/ or D-dimers(Baseline, 3, 6, 12 months)
研究者
Yi Ji
Principal Investigator
West China Hospital