Clinical trial NCT04144868: Normobaric Hyperoxia for Intracerebral Hemorrhage
Official title: Normobaric Hyperoxia for Intracerebral Hemorrhage A Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Normobaric Hyperoxia
Intracerebral Hemorrhage
Keywords: Intracerebral Hemorrhage
Normobaric Hyperoxia
Perihematomal Edema
Lead sponsor: Capital Medical University
Sponsor class: OTHER
Collaborators: name: Jiujiang University Affiliated Hospital
First posted: 2019-10-30
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Giving high-flow mask oxygen via oxygen storage face masks (100% O2, flow rate 8 L/min, 1 hour, four times daily, and 2 L/min via nasal catheter during intermittent periods, for 7 days) or not (2 L/min via nasal catheter for 7 days) at admission.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria:

1. supratentorial hematomas confirmed by admitted cranial computed tomography (CT), with the volume ranging from 10 to 30 mL;
2. age 18-80 years;
3. National Institute of Health Stroke Scale (NIHSS) ≥ 6 and Glasgow Coma Scale (GCS) \> 8 at admission;
4. onset-to-enrollment time ≤ 24 h;
5. signed informed consent.

Exclusion criteria:

1. a history of ICH, ischemic attack, brain tumor, brain trauma, and other intracranial injury or disorders;
2. pre-stroke modified ranking scales (mRS) ≥ 1;
3. life-threatening condition;
4. pre-stroke complicated with austere diseases such as cancer, heart failure, and respiratory failures;
5. severe liver and kidney disorders;
6. a history of respiratory diseases;
7. poor compliance;
8. participation in other clinical trials within the previous three months.

Primary outcomes:
measure: Percentage of Patients With mRS 0-3
timeFrame: 90 days
Secondary outcomes:
measure: NIHSS Scores
timeFrame: 3 days
measure: NIHSS Scores
timeFrame: 7 days
measure: NIHSS Scores
timeFrame: 14 days
measure: Glasgow Coma Scale
timeFrame: 3 days
measure: Glasgow Coma Scale
timeFrame: 7 days
measure: Glasgow Coma Scale
timeFrame: 14 days
measure: Barthel Index
timeFrame: 90 days
measure: mRS Distribution
timeFrame: 90 days
measure: Hematoma Volume
timeFrame: 3 days
measure: Hematoma Volume
timeFrame: 7 days
measure: Hematoma Volume
timeFrame: 14 days
measure: Absolute Perihematomal Edema Volume
timeFrame: 3 days
measure: Absolute Perihematomal Edema Volume
timeFrame: 7 days
measure: Absolute Perihematomal Edema Volume
timeFrame: 14 days
measure: Relative Perihematomal Edema Volume
timeFrame: 3 days
measure: Relative Perihematomal Edema Volume
timeFrame: 7 days
measure: Relative Perihematomal Edema Volume
timeFrame: 14 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Xuanwu Hospital, Captial Medical University
Study officials:
References:
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