An Open-Label, Dose-Escalation Study on the Safety, Tolerability and Preliminary Efficacy for Preventing Stroke-Associated Pneumonia of Intravenous Pump-Delivered Propranolol in Patients With Intracerebral Hemorrhage
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum tolerated Dose (MTD)
研究概览
简要总结
This is an open-label, dose-escalation study on the safety, tolerability and preliminary efficacy for preventing stroke-associated pneumonia of propranolol in patients with intracerebral hemorrhage. Propranolol is administered via intravenous pump continuously for 7 days.
详细描述
The accelerated titration (ATD) incorporated with Bayesian Optimal Interval design (BOIN) will be used to assess the DLT, safety and tolerability. Eligible patients will be enrolled in the ascending dose until MTD is established.The total number of patients is estimated to be approximately 30 patients for dose escalation, but the final total number of patients will depend upon the number of dose cohorts to reach MTD and patient number at each dose level. The preliminary efficacy of continuous intravenous infusion of propranolol for preventing stroke-associated pneumonia (SAP) in patients with severe intracerebral hemorrhage will be evaluated by analyzing the incidence and timing of SAP within 7 days of onset. Throughout the study period, all subjects receiving the investigational drug will undergo lymphocyte subset analysis and abdominal CT scans (to measure splenic volume) to exploratorily assess the impact of intravenous propranolol infusion on the immune function of these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 10 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged > 18 and ≤ 80 years of age;
- •Can be treated with the study drug within 24 h of symptom onset;
- •No fever or infection was observed upon admission;
- •NIHSS score ≥10;
- •Supratentorial parenchymal haematoma (≥10 mL);
- •GCS score ≥ 6;
- •Patients or their family members sign informed consent forms.
排除标准
- •Infections within the last 4 weeks;
- •Use of antibiotics within the last 2 weeks;
- •Known pre-ICH dysphagia;
- •Secondary intracerebral hemorrhage or intraventricular hemorrhage resulting from trauma, vascular malformation, aneurysm, coagulopathy, anticoagulant drugs, thrombolysis, post-infarction hemorrhage transformation, hematopathy, moyamoya disease, primary or metastatic tumor, venous sinus thrombosis, vasculitis, and other definite causes;
- •Previous disability with pre-ICH mRS score ≥ 2;
- •Brainstem hemorrhage;
- •Life expectancy less than 14 days;
- •Death appeared imminent;
- •Pregnancy or within 30 d of delivery;
- •Previous use (within 1 month) of β-blockers or reserpine;
- •Bronchial asthma or COPD;
- •Cardiogenic shock;
- •Degree II-III atrioventricular blocks;
- •Severe or acute heart failure;
- •Heart rate < 65 beats/min;
- •Known to be allergic to propranolol;
- •Severe liver or renal insufficiency;
- •History of malignant tumors;
- •Currently participating in other interventional clinical trials;
- •Currently, immunosuppressants and immunotherapies are being administered.
研究组 & 干预措施
Propranolol administered via intravenous pump for successive 7 days.
干预措施: Intravenous Pump-Delivered Propranolol (Drug)
结局指标
主要结局
Maximum tolerated Dose (MTD)
时间窗: up to 7 days
Determine MTD of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
Adverse events assessed according to NCI-CTCAE V6.0
时间窗: up to 7 days
Evaluate the safety of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
Dose limiting toxicities (DLT)
时间窗: up to 7 days
Evaluate the tolerability of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
次要结局
- The incidence of SAP within 7 days post-onset.(up to 7 days)
- Time to first diagnosis of SAP after onset.(up to 7 days)