CompARing Between CO2 Phenylephrine and Phenylephrine Only Treatment in Patients With proGrEssing Cerebral infarctioN

CompARing Between CO2 Phenylephrine and Phenylephrine Only Treatment in Patients With proGrEssing Cerebral infarctioN(CARBOGEN Trial)

Progressing stroke is associated poor functional outcome and neurological deficit.

Currently, no treatment for progressing stroke is recommended on the guideline.

Carbogen is a mixture of 5% CO2 with 95% O2. Carbogen is safe and it is used for the treatment of sudden sensory neural hearing loss or ocular ischemia.

CO2 dilate cerebral arteriole and concentration of CO2 is correlated with cerebral blood flow.

Increased cerebral blood flow following dilation of cerebral arteriole by CO2 might halt and revert progressing stroke.

Induced hypertension is alternative treatment of progressing stroke. Increasing blood pressure also induce cerebral blood flow. Phenylephrine is an α1 agonist, phenylephrine act on peripheral artery and little effect on cerebral artery or heart. Several studies reported that the effectiveness of phenylephrine on progressing stroke.

Therefore, this study will compare the effectiveness of carbogen + phenyleprhine versus phenlyephrine in progressing stroke patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: carbogen with or without phenyleprhine; Drug: phenylephrine

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥20 years
• Anterior circulation progressing stroke
• Neurological worsening either 1 point in NIHSS score or MRC grade

Exclusion Criteria:

• Age under 20 years.
• Patients with cerebral infarction who are at risk of cerebral edema as determined by the investigator.
• Patients with Moyamoya disease.
• Patients with severe cerebrovascular reactivity (CVR) impairment due to cerebral vascular stenosis, making study participation challenging as determined by the investigator.
• Patients unable to undergo CO2 treatment (e.g., panic disorder, anxiety disorders, or other psychiatric conditions).
• Patients with hypersensitivity to phenylephrine.
• Patients with persistent bradycardia (heart rate < 50 bpm).
• Patients with a history of hemorrhagic stroke or at risk of cerebral hemorrhage.
• Patients with a pre-stroke modified Rankin Scale (mRS) score ≥ 2, indicating impaired functional independence.
• Patients ineligible for phenylephrine treatment due to any of the following:

Myocardial infarction or unstable angina within the past 3 months. Cardiac ejection fraction < 25%. Ventricular arrhythmia. Systolic blood pressure > 200 mmHg. Serum creatinine > 2 mg/dL. Pregnancy.

• Use of monoamine oxidase (MAO) inhibitors.
• Patients who do not consent to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Phenylephrine group	Drug: phenylephrine; All patients will recevive phenyleprhine to increase blood pressure. Start phenylephrine with 0.5 mg/hr and titrate upto 3.5 mg/hr or systolic blod pressure 200 mmHg.
Experimental: Carbogen + phenylephrine group	Drug: carbogen with or without phenyleprhine; Patients will inhale carbogen gas for 10 minutes and rest for 50 minutes. All patients will recevive phenyleprhine to increase blood pressure. Start phenylephrine with 0.5 mg/hr and titrate upto 3.5 mg/hr or systolic blod pressure 200 mmHg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percent improvement of NIHSS score in each group	(baseline NIHSS score-post-treatment NIHSS score)/baseline NIHSS score×100	24 hours
difference of NIHSS score in each group	baseline NIHSS score-post-treatment NIHSS score	24 hours
percent improvement of MRC score in each group	(baseline MRC score-post-treatment MRC score)/baseline MRC score×100	within 24 hours
difference of MRC score in each group	baseline MRC score-post-treatment MRC score	difference of MRC score in each group
Saftety outcome: Side effect	Side effect (cerebral hemorrhage, myocardial infarction, Losing consciousness, difficulty breathing, dizziness, fatigue, headache, anxiety, etc)	within 7 days
Saftety outcome: discontinuing patients	Number of discontinuing patients due to side effects	within 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparision between groups by percent improvement of NIHSS score	(baseline NIHSS score-post-treatment NIHSS score)/baseline NIHSS score×100	24 hours
Comparision between groups by differnece of NIHSS score	baseline NIHSS score-post-treatment NIHSS score	24 hours
Comparision between groups by percent improvement in MRC score	(baseline MRC score-post-treatment MRC score)/baseline MRC score×100	within 24 hours
Comparision between groups by difference of MRC score	baseline MRC score-post-treatment MRC score	within 24 hours
Functional independencec	modifed Rankin score 0 to 2	3 months after onset

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 7, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: phenylephrine; CO2; carbogen; lacunar infarction; progressing stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Necrosis; Ischemia; Stroke; Ischemic Stroke; Cerebral Infarction; Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Respiratory System Agents; Cardiotonic Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Oxymetazoline; Phenylephrine
• Other Study ID Numbers: 4-2024-1415

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