An Open-Label, Dose-Escalation Study on the Safety, Tolerability and Preliminary Efficacy for Preventing SAP by Intravenous Pump-Delivered Propranolol in Patients With ICH

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug Intravenous Pump-Delivered Propranolol
  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, administere

Primary outcome measures

• Maximum tolerated Dose (MTD) [Time frame: up to 7 days]
• Adverse events assessed according to NCI-CTCAE V6.0 [Time frame: up to 7 days]
• Dose limiting toxicities (DLT) [Time frame: up to 7 days]

Secondary outcome measures (2)

• The incidence of SAP within 7 days post-onset. [Time frame: up to 7 days]
• Time to first diagnosis of SAP after onset. [Time frame: up to 7 days]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• Department of Neurosurgery , Tangdu Hospital, Fourth Military Medical University — Xi'an

Identifiers

NCT: NCT07528235 · PROCHASE-Dose-Escalation

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗