Correcting Hypocapnia in Aneurysmal Subarachnoid Hemorrhage.

January 6, 2026 updated by: Renzhi Wang, The Chinese University of Hong Kong, Shenzhen

Safety and Efficacy of Normobaric Facemask Oxygen for Hypocapnia in Aneurysmal Subarachnoid Hemorrhage(FOCAL): A Prospective, Multicenter, Proof-of-concept Pilot Study

Based on the clinical observation that over half of the patients in the management of aneurysmal subarachnoid hemorrhage(aSAH) present with spontaneous hyperventilation, which is significantly associated with delayed cerebral ischemia and poor neurological outcomes, this prospective pilot study is designed to investigate the safety and efficacy of normobaric facemask oxygen for hypocapnia in aSAH.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Spontaneous hyperventilation (SH) is highly prevalent following aneurysmal subarachnoid hemorrhage (aSAH) and is significantly associated with poor neurological outcomes.The core pathophysiological mechanism involves hypocapnia induced by hyperventilation, which triggers cerebral vasoconstriction and consequently leads to a decrease in cerebral blood flow (CBF).Although this response may transiently reduce intracranial pressure, persistent cerebral vasoconstriction markedly increases the risk of delayed cerebral ischemia (DCI) and secondary brain injury. Therefore, maintaining the arterial partial pressure of carbon dioxide (PaCO2) within the physiological range of mmHg is recommended to minimize the detrimental effects of hypocapnia.

Currently, there is a lack of standardized management strategies for hypocapnia resulting from SH after aSAH. Based on physiological principles, low-flow (<5 L/min) oxygen delivery via a facemask may effectively correct hypocapnia by promoting the rebreathing of carbon dioxide within the dead space of the facemask.10 A randomized controlled trial investigating psychogenic hyperventilation syndrome provides preliminary evidence for this approach, demonstrating that low-flow (3 L/min) facemask oxygen therapy can relieve symptoms more rapidly and improve patient comfort compared to traditional breathing training.11

However, high-level evidence regarding the safety, efficacy, and impact on neurological outcomes of using low-flow facemask oxygen therapy (functioning as a rebreathing mask) as a targeted intervention for correcting hypocapnia in aSAH patients remains scarce. Consequently, this proof-of-concept prospective study aims to systematically evaluate the operational safety and clinical effectiveness of rebreathing facemask oxygen therapy for correcting hypocapnia in patients with aSAH.

Study Type

Observational

Enrollment (Estimated)

80

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518000
        • School of Medicine Chinese University of Hong Kong-SHENZHEN
        • Contact:
        • Principal Investigator:
          • Xinyu Yang, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Aneurysmal Subarachnoid Hemorrhage Patients with Hypocapnia.

Description

Inclusion Criteria:

  1. Age > 18 years.
  2. Confirmed diagnosis of aneurysmal subarachnoid hemorrhage (aSAH), with the presence of an aneurysm verified by computed tomography (CT), CT angiography (CTA), or digital subtraction angiography (DSA).
  3. Hunt-Hess grade II-IV.
  4. Presence of hypocapnia on arterial blood gas analysis, defined as PaCO2 < 35 mmH;
  5. PaO2 > 90 mmHg.

Exclusion Criteria:

  1. Presence of brain herniation or refractory intracranial hypertension, defined as a baseline intracranial pressure (ICP) > 25 mmHg that responds poorly to conventional ICP-lowering therapy;
  2. Primary respiratory diseases (e.g., chronic obstructive pulmonary disease, severe asthma) known to cause chronically elevated baseline PaCO2;
  3. Severe acid-base disturbances other than respiratory alkalosis.
  4. Severe cardiac insufficiency, severe hepatic or renal dysfunction, malignant tumors, or other severe comorbidities that significantly impact prognosis;
  5. Before the onset of the disease, the mRS score was greater than 2, and there were other factors causing disability.
  6. Life expectancy < 3 months;
  7. Any other condition deemed by the investigator to pose a high risk warranting exclusion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Normobaric Facemask Oxygen
Patients who received oxygen via a rebreathing facemask (ensuring no one-way valve is present), with a fractional inspired oxygen (FiO2) of 25-40% and an oxygen flow rate of ≤ 5 L/min.
Behavioral: Normobaric Facemask Oxygen

Oxygen is to be delivered via a rebreathing facemask (ensuring no one-way valve is present), with a fractional inspired oxygen (FiO2) of 25-41% and an oxygen flow rate of ≤ 5 L/min.

The goals are to maintain patient SpO2 > 95%, PaCO2 between 35-42 mmHg, and, where feasible (particularly in centers with the capability for monitoring), an intracranial pressure (ICP) of < 15 mmHg.
Control group
Patients who received oxygen via nasal cannula or did not receive oxygen therapy.
Behavioral: control group
Using nasal cannula for oxygen inhalation or not using oxygen inhalation at all. Monitor and record the patient's SpO2, systolic blood pressure, diastolic blood pressure, PaCO2, and also monitor the intracranial pressure (ICP) at a center with monitoring capabilities.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
modified Rankin Scale (mRS) >3
Time Frame: 90-day follow-up visit
The poor neurological outcome was considered to be mRs >3, indicating severe disability or death. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. (Score Description: 0---No symptoms at all. 1---No significant disability despite symptoms; able to carry out all usual duties and activities. 2---Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3---Moderate disability; requiring some help, but able to walk without assistance. 4--- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5---Severe disability; bedridden, incontinent and requiring constant nursing care and attention. 6---Dead.
90-day follow-up visit
Incidence of delayed cerebral injury (DCI)
Time Frame: 30 days after onset
The presence of new focal neurological signs or a documented decrease in the level of consciousness persisting for at least 1 hour (or a drop of at least 1 point in the total Glasgow Coma Scale score), deemed to be of ischemic origin, after ruling out other causes (such as hydrocephalus, toxic-metabolic disturbances, or seizures); or identification of a new cerebral infarction on CT or MRI imaging.
30 days after onset

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montreal Cognitive Assessment (MoCA)
Time Frame: 90-day follow-up visit
Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA), a standardized screening tool with scores ranging from 0 to 30, where higher scores indicate better cognitive performance and lower scores reflect greater cognitive impairment. Measure mean score or median compared between groups. And the rate of MoCA score of 20 or less between groups.
90-day follow-up visit
Cerebral Vasospasm
Time Frame: Participants will be followed for the duration of the hospital stay, an expected average of 2 weeks
Incidence of moderate and severe radiographic cerebral vasospasm (catheter angiogram, CTA, MRA) or incidence OR moderate and severe vasospasm by transcranial doppler (TCD) criteria.
Participants will be followed for the duration of the hospital stay, an expected average of 2 weeks
Glasgow Coma Score(GCS)
Time Frame: Enrollment, 30 days after onset, and 90-day follow-up visit
The Glasgow Outcome Scale was used as secondary outcomes. The level of consciousness was assessed using the Glasgow Coma Scale (GCS), a standardized scale ranging from 3 to 15, where higher scores indicate a better neurological status (i.e., a higher level of consciousness), and lower scores reflect more severe impairment.
Enrollment, 30 days after onset, and 90-day follow-up visit
The modified Rankin Scale (mRS)
Time Frame: 30 days after onset
Shift analysis of mRS scores at 30 days after onset. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. (Score Description: 0---No symptoms at all. 1---No significant disability despite symptoms; able to carry out all usual duties and activities. 2---Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3---Moderate disability; requiring some help, but able to walk without assistance. 4--- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5---Severe disability; bedridden, incontinent and requiring constant nursing care and attention. 6---Dead. The higher scores indicate worse functional disability and lower scores reflect better functional independence.
30 days after onset
modified Rankin Scale (mRS)
Time Frame: 30 days after onset
The rate of modified Rankin Scale (mRS) score > 3. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. (Score Description: 0---No symptoms at all. 1---No significant disability despite symptoms; able to carry out all usual duties and activities. 2---Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance. 3---Moderate disability; requiring some help, but able to walk without assistance. 4--- Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance. 5---Severe disability; bedridden, incontinent and requiring constant nursing care and attention. 6---Dead. The higher scores indicate worse functional disability and lower scores reflect better functional independence.
30 days after onset
Barthel Index (BI) score
Time Frame: 90-day follow-up visit
Activities of daily living were evaluated using the Barthel Index (BI), a functional assessment scale ranging from 0 to 100, where higher scores indicate greater independence in daily activities and lower scores reflect more severe functional dependence.
90-day follow-up visit
All-cause mortality
Time Frame: 90-day follow-up visit
Death caused by any reason.
90-day follow-up visit
Complication of severe dependent survival
Time Frame: 90-day follow-up visit
eg, chest or other infections
90-day follow-up visit
Treated aneurysm rebleeding
Time Frame: 90-day follow-up visit
Treated aneurysm rebleeding
90-day follow-up visit
Probable or definite bleed from another aneurysm
Time Frame: 90-day follow-up visit
Probable or definite bleed from another aneurysm
90-day follow-up visit
Incidence of adverse events
Time Frame: 90-day follow-up visit
Ischaemic stroke, Other intracranial haemorrhage, Cardiac, Cancer, Suicide, Renal failure, Infections not related to dependent survival, Other causes (eg, trauma, perforated ulcer, pulmonary embolus, neurodegenerative)
90-day follow-up visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Chinese University of Hong Kong, Shenzhen

Investigators

  • Study Chair: Renzhi Wang, MD, CUHK-Shenzhen
  • Principal Investigator: Xinyu Yang, CUHK-Shenzhen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

October 30, 2026

Study Registration Dates

First Submitted

December 17, 2025

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 15, 2026

Study Record Updates

Last Update Posted (Actual)

January 15, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CUHKShenzhen

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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