Normobaric Hyperoxia for Intracerebral Hemorrhage

Phase 2

Completed

Conditions: Normobaric Hyperoxia
Intracerebral Hemorrhage

Interventions: Other: Normobaric Oxygen

Registration Number: NCT04144868

Lead Sponsor: Capital Medical University

Brief Summary: Perihematoma edema (PHE), as the major injury for intracranial hemorrhage (ICH) involves more than the initial tissue damage induced directly by the hematoma. How to improve hypoxia in perihematoma seems to be a promising therapeutic candidate paradigm for ICH due to its pivotal role in the pathogenesis of perihematomas. Normobaric hyperoxia (NBO), supplied by a face mask (such as oxygen storage face mask) with atmosphere pressure (1ATA = 101.325 kPa, 100% O2), has been considered a safe, convenient, and promising therapy for correcting various diseases and thus garnered great attention in recent years. The previous study identified that early NBO could attenuate blood-brain barrier damage, rescue penumbra and finally improve the prognosis of ischemic stroke in patients with delayed rt-PA treatment. Therefore, given the profound effectiveness in the ischemic penumbra, we hypothesized that NBO might yield additional benefits for the ischemic-hypoxic tissues surrounding the hematoma in patients with ICH. Although many clinical trials have shown the effectiveness and safety of NBO in treating ischemic stroke, there is currently a lack of trials focusing on using NBO to treat ICH. Accordingly, we conducted a proof-of-concept, single-center, randomized controlled trial to evaluate the safety and efficacy of NBO in treating ICH patients so as to explore an innovative adjuvant therapy for ICH.

Detailed Description: Intracerebral hemorrhage (ICH) is an intractable and life-threatening stroke subtype that imposes a significant impact on people's well-being and quality of life. ICH-induced mechanical compression to the surrounding brain tissue is a major injury that increases intracranial pressure (ICP). High ICP can decrease cerebral blood flow (CBF) and influence cerebral metabolism in perihematoma and even the whole brain. Decreased aerobic metabolism and perfusion in perihematomal injury can exacerbate edema and enlarge hematoma. Moreover, secondary injury in the perihematoma, such as ischemia, oxidative stress, inflammatory response, and protease release, involves more than the initial tissue damage induced directly by the hematoma. Theoretically, low CBF and abnormal metabolism in ICH patients expose the brain tissue to the ischemic-hypoxic condition, which is similar to that in the ischemic penumbra in stroke. Therefore, the key to treating ICH is to find an approach that can rescue the perihematoma. Improving hypoxia in perihematoma seems to be a promising therapeutic candidate paradigm for ICH due to its pivotal role in the pathogenesis of perihematomas.

Normobaric hyperoxia (NBO), supplied by a face mask (such as oxygen storage face mask) with atmosphere pressure (1ATA = 101.325 kPa, 100% O2), has been considered a safe, convenient, and promising therapy for correcting various diseases and thus garnered great attention in recent years. The effectiveness of NBO on ischemic stroke (IS) has been fully identified. A plethora of studies show that NBO is capable of increasing the partial pressure of oxygen (PO2), elevating the blood flow and volume, protecting the blood-brain barrier (BBB), improving oxidative metabolism, reducing free radical damage, and even relieving inflammatory response in the penumbra. Rapid amelioration of hypoxia in brain tissue can restore brain dysfunction and improve clinical prognoses. Likewise, NBO is also regarded as a promising method for treating ICH. An animal study found that NBO for a period of 6 h per day for 3 consecutive days imposed a remarkable neuroprotective effect in rat ICH, improved neurological function, reduced brain edema, downregulated HIF-1α and VEGF expression and showed a reduction in apoptotic cells in the perihematoma. Although many clinical trials have shown the effectiveness and safety of NBO in treating ischemic stroke, there is currently a lack of trials focusing on using NBO to treat ICH. Accordingly, we conducted a proof-of-concept, single-center, randomized controlled trial to evaluate the safety and efficacy of NBO in treating ICH patients so as to explore an innovative adjuvant therapy for ICH.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 96

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: NBO group	Normobaric Oxygen	For eligible patients into the group of cerebral hemorrhage,Low-flow oxygen is delivered through the facemask at a rate of 8 L/min, once a hour, every 4 hours. Regular treatment is based on associated guidelines for ICH .

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With mRS 0-3	90 days	modified Rankin Scale (mRS), an ordinal global disability scale ranging from 0 (no symptoms) to 6 (death)

Secondary Outcome Measures

Name	Time	Method
Hematoma Volume	14 days	Hematoma volume in cranial CT scan, calculated by the software from United Imaging (United Imaging Healthcare Co., Ltd., Shanghai, China).
Absolute Perihematomal Edema Volume	14 days	Absolute perihematomal edema in cranial CT scan, calculated by the software from United Imaging (United Imaging Healthcare Co., Ltd., Shanghai, China).
NIHSS Scores	14 days	The NIHSS is commonly used to evaluate neurological deficits in stroke and comprises five items in 11 fields of different neurological statuses (scores range from 0-42, representing normal to severe neurological deficits).
Glasgow Coma Scale	14 days	Glasgow Coma Scale is a practical method for the evaluation of impairment of conscious level in response to defined stimuli, which contains three parts, including eye-opening, verbal response, and motor response (scores range from 3-15, representing deep coma to normal).
Barthel Index	90 days	Barthel Index represents functional status at follow-up time, the scores of which range from 0 (complete dependence) to 100 (complete independence) measured by several items, including feeding, bathing, grooming, dressing, bowels, bladder, toilet use, transfers, and stairs.
mRS Distribution	90 days	modified Rankin Scale (mRS), an ordinal global disability scale ranging from 0 (no symptoms) to 6 (death)
Relative Perihematomal Edema Volume	14 days	The relative perihematomal edema was calculated by dividing the absolute perihematomal edema volume by the baseline hematoma volume to obtain a dimensionless ratio.