Hemorrhagic Brainstem Cavernous Malformations Treatment With Sirolimus: a Randomized, Placebo-controlled Pilot Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 1
- 主要终点
- The primary outcome is to explore the safety of sirolimus in the management of BSCMs.
研究概览
简要总结
The aim of this pilot phase trial is to assess the safety and tolerability, and estimate the efficacy of sirolimus in reducing the incidence of ICH during high-risk periods for rebleeding, compared to placebo. This pilot trial will inform the design of a future definitive clinical trial on sirolimus treatment for CCM.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
A double-blind design means that throughout the entire study, neither the participating patients nor the investigators are aware of which treatment group the patients are assigned to, in order to minimize potential biases. The blinding level is double-blind, which means that both the patients in the treatment group and those in the control group, as well as the investigators, are unaware of the treatment the patients receive, ensuring objectivity and reliability of the study results.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years, any gender;
- •Patients who have experienced their first symptomatic BSCM ICH within the six months before randomisation;
- •Diagnosed with solitary BSCM through T2, GRE/T2*, or SWI MR imaging;
- •ICH within or around the BSCM confirmed by CT /MR;
- •Capable of signing an informed consent form with the accompaniment and understanding of a guardian.
排除标准
- •Cancer history;
- •Pregnancy or lactation;
- •Sirolimus/starch allergy;
- •Modified Rankin Scale (mRS) score 5, respiratory failure or currently severe bleeding requiring life support treatment;
- •Abnormal liver and/or kidney function (transaminase levels greater than 50, creatinine greater than 110), abnormal white blood cell/platelet counts (white blood cell count below 3.5 or above 9.5 x 109/L or exceeding normal values, platelet count below 100 or above 300);
- •History of previous immunosuppressive therapy;
- •History of prior surgical intervention for CCM ;
- •History of prior cranial radiation therapy ;
- •Familial CCM or people with multiple CCM;
- •Patients with concurrent acute active infections (e.g., severe bacterial, viral, or fungal infections);
- •Uncontrolled diabetes mellitus;
- •Currently participating in another clinical trial;
- •Patient unwilling/unable to undergo MRI.
- •Co-administration of drugs affecting CYP3A4 enzymes (ketoconazole, voriconazole, itraconazole, telithromycin, clarithromycin).
研究组 & 干预措施
High-dose sirolimus group
Participants will receive oral sirolimus with a target blood concentration of 9-15ng/ml continuously for 12 months.
干预措施: Sirolimus (Drug)
Low-dose sirolimus group
Participants will receive oral sirolimus with a target blood concentration of 3-7ng/ml continuously for 12 months
干预措施: Sirolimus (Drug)
Placebo control group
Participants will receive oral placebo(starch formulation) for 12 months.
干预措施: Starch flake (Drug)
结局指标
主要结局
The primary outcome is to explore the safety of sirolimus in the management of BSCMs.
时间窗: 24 months
A serious adverse event is an SAE occurring during any study phase that fullfils one or more of the following criteria: i. Results in death, ii. Is life-threatening, iii. Requires inpatient hospitalization or prolongation of existing hospitalization, iv. Results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, v. Is an important medical event that may jeopardize the patient or may require medical intervention to prevent one of the outcomes listed above. SAE will be assessed at each follow-up visit (15 days, 2 months, 6 months, 12 months, 18 months, 24 months). During the trial, participants can promptly report potential SAEs to the research team via the telephone. We will establish continuous, real-time communication with patients via the telephone, facilitating round-the-clock reporting of potential endpoints or adverse reactions to the clinical trial investigators.
次要结局
- We will measure the tolerability of sirolimus in the management of BSCMs.(24 months)
- We will measure the occurrence of recurrent ICH from the BSCM within 24 months.(24 months)
- We will measure the efficacy outcomes in MR(24 months)
- We will measure several the quality of life(24 months)
研究者
Wei Zhu
Vice director of neurosurgey department
Huashan Hospital