Clinical trial NCT04839224: Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)
Official title: Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: CO2
carbogen
phenylephrine
lacunar infarction
progressive stroke
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2021-04-09
Enrollment: 3
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 neurological worsening after lacunar infarction, the carbogen group and the phenylephrine group will be randomized by 1: 1.
3. Patients will be enrolled from April 2021 to December 2022 (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: Lacunar infarction is an ischemic stroke occurred by small perforating artery occlusion . Twenty percent of ischemic stroke is lacunar infarction.

However, outcome of lacunar infarction is excellent, about 20-40% patients are suffered neurological worsening.

Progressive lacunar infarction is associated poor functional outcome and neurological deficit.

Currently, no treatment for progressive lacunar infarction is recommended on the guideline.

Several small study reported that phenylephrine and magnesium may be helpful for progressive lacunar infarction.

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.

Lacunar infarction is small and perfused with marginal flow by neighboring perforating arteriole.

Increased cerebral blood flow following dilation of cerebral arteriole by CO2 might halt and revert progressive lacunar infarction.

Induced hypertension is alternative treatment of progressive lacunar infarction. 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 versus phenylephrine in lacunar infarction patients who suffered neurological worsening.


Eligibility criteria: Inclusion Criteria:

1. Age ≥20 years
2. Anterior circulation progressive lacunar infarction.
3. Neurological worsening either 1 point in NIHSS score or MRC grade

Exclusion Criteria:

1. Age \<20
2. Cortical infarction
3. Posterior circulation lacunar infarction
4. Relevant artery stenosis more than 50% or occlusion
5. Moyamoya disease
6. Difficulty in inhalation of Carbogen (panic, severe anxiety disorder)
7. Drug allergy for phenylephrine
8. Persistent bradycardia (pulse rate \< 50 /min)
9. History of hemorrhagic stroke
10. Pre-stroke mRS ≥2

Primary outcomes:
measure: percent improvement of NIHSS score in each group
timeFrame: 48 hours
measure: difference of NIHSS score in each group
timeFrame: 48 hours
measure: percent improvement of MRC score in each group
timeFrame: within 48 hours
measure: difference of MRC score in each group
timeFrame: within 48 hours
measure: Safety outcome: Side effect
timeFrame: within 7 days
measure: Safety outcome: discontinuing patients
timeFrame: within 7 days
Secondary outcomes:
measure: Comparison between groups by percent improvement of NIHSS score
timeFrame: 48 hours
measure: Comparison between groups by difference of NIHSS score
timeFrame: 48 hours
measure: Comparison between groups by percent improvement in MRC score
timeFrame: within 48 hours
measure: Comparison between groups by difference of MRC score
timeFrame: within 48 hours
measure: Functional independence
timeFrame: upon discharge, 3 months after onset
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: Department of Neurology, Yonsei University College of Medicine
name: Hyo Suk Nam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: