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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
PREVENTION
Masking
NONE
Enrollment
30
During the dose escalation phase, the proposed five dose levels of intravenous pump infusion of propranolol hydrochloride injection are as follows: * 0.01 mg/kg/h, administered as one group over 2 hours; repeated every 6 hours, with 3 groups per 24 hours, avoiding the period from 02:00 to 06:00 at night; * 0.02 mg/kg/h, administered as one group over 2 hours; repeated every 6 hours, with 3 groups per 24 hours, avoiding the period from 02:00 to 06:00 at night; * 0.03 mg/kg/h, administered as one group over 2 hours; repeated every 6 hours, with 3 groups per 24 hours, avoiding the period from 02:00 to 06:00 at night; ④ 0.04 mg/kg/h, administered as one group over 2 hours; repeated every 6 hours, with 3 groups per 24 hours, avoiding the period from 02:00 to 06:00 at night; ⑤ 0.05 mg/kg/h, administered as one group over 2 hours; repeated every 6 hours, with 3 groups per 24 hours, avoiding the period from 02:00 to 06:00 at night.
Department of Neurosurgery , Tangdu Hospital, Fourth Military Medical University
Xi'an, Shaanxi, China
Maximum tolerated Dose (MTD)
Determine MTD of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
Time frame: up to 7 days
Adverse events assessed according to NCI-CTCAE V6.0
Evaluate the safety of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
Time frame: up to 7 days
Dose limiting toxicities (DLT)
Evaluate the tolerability of intravenous pump-delivered propranolol in patients with intracerebral hemorrhage
Time frame: up to 7 days
The incidence of SAP within 7 days post-onset.
Incidence of stroke-associated pneumonia within 7 days after onset of ICH
Time frame: up to 7 days
Time to first diagnosis of SAP after onset.
Time to first diagnosis of SAP after onset of ICH
Time frame: up to 7 days
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