Comparing Between CO2 and Phenylephrine Treatment in Patients With Progressive Lacunar Infarction (CARBOGEN Study)

NCT04839224 | Terminated Phase 3 DMC

• 1 other identifier: 4-2020-1491
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ischemic Stroke

Keywords

CO2; carbogen; phenylephrine; lacunar infarction; progressive stroke

Outcome Measures

Primary Outcomes (6)

• percent improvement of NIHSS score in each group

  (baseline NIHSS score-post-treatment NIHSS score)/baseline NIHSS score×100

  48 hours

• difference of NIHSS score in each group

  baseline NIHSS score-post-treatment NIHSS score

  48 hours

• percent improvement of MRC score in each group

  (baseline MRC score-post-treatment MRC score)/baseline MRC score×100

  within 48 hours

• difference of MRC score in each group

  baseline MRC score-post-treatment MRC score

  within 48 hours

• Safety outcome: Side effect

  Side effect (cerebral hemorrhage, myocardial infarction, Losing consciousness, difficulty breathing, dizziness, fatigue, headache, anxiety, etc)

  within 7 days

• Safety outcome: discontinuing patients

  Number of discontinuing patients due to side effects

  within 7 days

Secondary Outcomes (5)

• Comparison between groups by percent improvement of NIHSS score

  48 hours

• Comparison between groups by difference of NIHSS score

  48 hours

• Comparison between groups by percent improvement in MRC score

  within 48 hours

• Comparison between groups by difference of MRC score

  within 48 hours

• Functional independence

  upon discharge, 3 months after onset

Study Arms (2)

Carbogen group

EXPERIMENTAL

Drug: carbogen

Phenylephrine group

ACTIVE COMPARATOR

Drug: phenylephrine

Interventions

carbogen DRUG

Patients will inhale carbogen gas for 10 minutes and rest for 50 minutes.

Carbogen group

phenylephrine DRUG

Start phenylephrine with 0.5 mg/hr and titrate upto 3.5 mg/hr or systolic blod pressure 200 mmHg.

Phenylephrine group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Ischemic Stroke; Stroke, Lacunar

Interventions

carbogen; Phenylephrine

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Cerebral Small Vessel Diseases; Thrombotic Stroke; Brain Infarction; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Study Officials

• Hyo Suk Nam, MD, PhD

  Department of Neurology, Yonsei University College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Three months after discharge, the independence assessment will be performed by the researcher who don't know the patients group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 6, 2021
• First Posted: April 9, 2021
• Study Start: April 5, 2021
• Primary Completion: October 18, 2022
• Study Completion: September 12, 2024
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)