Clinical trial NCT06770426: CompARing Between CO2 Phenylephrine and Phenylephrine Only Treatment in Patients With proGrEssing Cerebral infarctioN
Official title: CompARing Between CO2 Phenylephrine and Phenylephrine Only Treatment in Patients With proGrEssing Cerebral infarctioN(CARBOGEN Trial)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: CO2
carbogen
phenylephrine
lacunar infarction
progressing stroke
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2025-01-13
Enrollment: 40
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1. The study is a single center, prospective, randomized, open-label trial with blinded end-point assessment (PROBE) design study.
2. For the patients with progressing stroke, the carbogen + phenylphrine group and the phenylephrine only group will be randomized by 1: 1 through web-based app.
3. Patients will be enrolled from February 2025 to September 2027 (based on the date of stroke).
4. We will collect medical history, laboratory findings, neurological scores, and functional recovery.
5. Functional recovery scores are performed by independent researchers in the blind state.
6. All data is collected using e-CRF, and the image study will be anonymized and sent to the central adjudication.
7. Central adjudication will review the image study.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: percent improvement of NIHSS score in each group
timeFrame: 24 hours
measure: difference of NIHSS score in each group
timeFrame: 24 hours
measure: percent improvement of MRC score in each group
timeFrame: within 24 hours
measure: difference of MRC score in each group
timeFrame: difference of MRC score in each group
measure: Saftety outcome: Side effect
timeFrame: within 7 days
measure: Saftety outcome: discontinuing patients
timeFrame: within 7 days
Secondary outcomes:
measure: Comparision between groups by percent improvement of NIHSS score
timeFrame: 24 hours
measure: Comparision between groups by differnece of NIHSS score
timeFrame: 24 hours
measure: Comparision between groups by percent improvement in MRC score
timeFrame: within 24 hours
measure: Comparision between groups by difference of MRC score
timeFrame: within 24 hours
measure: Functional independencec
timeFrame: 3 months after onset
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
References: