Citicoline in Ischemic Stroke, a Randomized Trial

Citicoline in Ischemic Stroke, a Randomized Placebo-controlled Trial

Along with the current clinical trial, the efficacy and safety of a 1000 mg daily citicoline administered within 24 hours of the first-ever ischemic stroke and lasted 12 months compared to placebo were assessed through MoCA, NIHSS, mRS, and possible adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Drug: Citicoline; Drug: Placebo

Detailed Description

The investigators conducted a single-blinded, placebo-controlled, randomized controlled trial between December 2023 and December 2024 after approval of the ethical committee of the faculty of medicine at Kafr el-Sheik University.

The investigators got written informed consent from all eligible patients or their first order of kin before randomization.

The study will comprise 2 arms citicoline arm, which consists of 400 patients who received 1000 mg citicoline once daily for 12 months, and the placebo arm, consisting of 400 patients who received a placebo once daily for 12 months; all the patients in the two groups received open-label double antiplatelet in the form of 75 mg aspirin. and 75 mg clopidogrel for three weeks, followed by a single antiplatelet in the form of 75 mg clopidogrel for the rest of our trial.

Study Procedures:

Every patient in our study will undergo:

clinical workup: History, clinical assessment & NIHSS, and the Modified Rankin Scale and MoCA scale were recorded at baseline and then after 3 months, 6 months, and 12 months as a follow-up

Detection of Risk Factors & Profiles:

Echocardiography TTE: in indicated patients ECG Monitoring: daily ECG monitoring will be performed in indicated patients. 3- Carotid Duplex: carotid duplex in indicated patients.

4- ESR & Lipid Profile& liver functions: All will be tested routinely for all patients.

Imaging Follow UP Non-contrast CT brain on admission and MRI (stroke protocol; T1W, T2W, FLAIR, DWI, T2 Echo Gradient, MRA of all intra-cerebral vessels).

CT brain: Any patient with unexplained clinical deterioration at any time throughout his/her hospital stay will be urgently imaged by CT.

Primary End Point:

The primary efficacy outcome was the MoCA score after 6 months, the primary safety outcome was the rate of treatment-related adverse effects assessed by a follow-up questionnaire after 6 months.

• Secondary End Point: the secondary efficacy outcomes were: the MoCA after 12 months, mRS after 6 months, and mRS after 12 months, and the secondary safety outcome was the rate of treatment-related adverse effects assessed by a follow-up questionnaire after 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: mohamed G Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
• Study Contact Backup: Name: sherihan R. ahmed, MD; Phone Number: 2001113432342; Email: sherihanrezk2016@gmail.com

Study Locations

• Egypt
  • Kafr Ash Shaykh, Egypt, 33511
    • Recruiting
    • Kafr elsheikh university hospital
    • Contact: mohamed G. Zeinhom, MD; Phone Number: 2001009606828; Email: mohamed_gomaa@med.kfs.edu.eg
    • Contact: sherihan R ahmed, MD; Phone Number: 2001007481842; Email: sherihanrezk2016@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male & female patients will be included
• Age more than 18 years.
• Patients must be treated within the first 24 hours of their initial stroke symptoms onset.
• Patients not eligible to receive TPA.
• Patients with a measurable focal neurological deficit (NIHSS score ≥ 4 and less than 21) lasting at least 60 minutes.This deficit must persist from the onset and up to the time of treatment without clinically significant improvement

Exclusion Criteria:

• Patients eligible for rTPA treatment.
• Patients with any type of aphasia
• Patients in coma: patients having a score of 2 or higher in the items regarding the level of consciousness in the NIHSS.
• CT or conventional MRI evidence of any structural brain disorder other than ischemic stroke.
• History of ventricular dysrhythmias, acute myocardial infarction within 72 hours before enrolment, unstable angina, decompensated congestive heart failure, or any other acute, severe, uncontrollable, or sustained cardiovascular condition that, in the Investigator's opinion, may interfere with effective participation in the study.
• Previous disorders that may confound the interpretation of the neurological scales.
• Drug addiction-related disorders.
• Pre-existing dementia, when dementia implies a disability, measured as a score of 2 or higher in the previous mRS.
• Patients under current treatment with citicoline.
• concomitant administration of other neuroprotectant drugs (such as nimodipine, vinpocetine, piracetam, cerebrolysine).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: citicoline arm; The citicoline arm consists of 400 patients who received 1000 mg citicoline once daily for 12 months and an open-label double antiplatelet in the form of 75 mg aspirin and 75 mg clopidogrel for three weeks, followed by a single antiplatelet in the form of 75 mg clopidogrel for the rest of our trial.	Drug: Citicoline; The citicoline arm consists of 400 patients who received 1000 mg citicoline once daily for 12 months, and an open-label double antiplatelet in the form of 75 mg aspirin, and 75 mg clopidogrel for three weeks, followed by a single antiplatelet in the form of 75 mg clopidogrel for the rest of our trial.; Other Names: group A
Placebo Comparator: placebo arm; The placebo arm consists of 400 patients who received a placebo capsule daily for 12 months and an open-label double antiplatelet in the form of 75 mg aspirin and 75 mg clopidogrel for three weeks, followed by a single antiplatelet in the form of 75 mg clopidogrel for the rest of our trial.	Drug: Placebo; The placebo arm consists of 400 patients who received a placebo capsule once daily for 12 months, an open-label double antiplatelet in the form of 75 mg aspirin, and 75 mg clopidogrel for three weeks, followed by a single antiplatelet in the form of 75 mg clopidogrel for the rest of our trial.; Other Names: group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Value of Montreal Cognitive Assessment (MoCA)	MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Its score ranges from zero to 30 points; the normal value is from 26 to 30; mild cognitive impairment ranges from 18 to 25, Moderate cognitive impairment ranges from 10 to 17, and severe cognitive impairment is below 10 points.	6 months
Rate of drug-related complications after 6 months	All side effects related to the drugs in our study will be reported	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Value of Montreal Cognitive Assessment (MoCA)	MoCA is a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. Its score ranges from zero to 30 points; the normal value is from 26 to 30; mild cognitive impairment ranges from 18 to 25, Moderate cognitive impairment ranges from 10 to 17, and severe cognitive impairment is below 10 points.	12 months
Value of Modified Rankin Scale (mRS) at 6 months	mRS Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability; its value ranges from 0 to 6; the lower the score, the better the stroke outcome; favorable stroke outcome is considered with mRS value equals two or less.	6 months
Value of Modified Rankin Scale (mRS) at 12 months	mRS Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability; its value ranges from 0 to 6; the lower the score, the better the stroke outcome; favorable stroke outcome is considered with mRS value equals two or less.	12 months
Rate of drug-related complications after 12 months	All side effects related to the drugs in our study will be reported	12 months

Collaborators and Investigators

• Sponsor: Kafrelsheikh University
• Investigators: Study Director: Mohamed G. Zeinhom, MD, neurology department kafr el-sheikh university

Publications and helpful links

General Publications

• Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006 May 27;367(9524):1747-57. doi: 10.1016/S0140-6736(06)68770-9.
• Adibhatla RM, Hatcher JF. Citicoline mechanisms and clinical efficacy in cerebral ischemia. J Neurosci Res. 2002 Oct 15;70(2):133-9. doi: 10.1002/jnr.10403.
• Cho HJ, Kim YJ. Efficacy and safety of oral citicoline in acute ischemic stroke: drug surveillance study in 4,191 cases. Methods Find Exp Clin Pharmacol. 2009 Apr;31(3):171-6. doi: 10.1358/mf.2009.31.3.1364241.
• Garcia-Cobos R, Frank-Garcia A, Gutierrez-Fernandez M, Diez-Tejedor E. Citicoline, use in cognitive decline: vascular and degenerative. J Neurol Sci. 2010 Dec 15;299(1-2):188-92. doi: 10.1016/j.jns.2010.08.027. Epub 2010 Sep 27.

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2023
• Primary Completion (Estimated): June 29, 2024
• Study Completion (Estimated): December 29, 2024

Study Registration Dates

• First Submitted: January 7, 2024
• First Submitted That Met QC Criteria: January 7, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 7, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ischemic stroke; Egypt; citicoline
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Nootropic Agents; Cytidine Diphosphate Choline
• Other Study ID Numbers: 2391988

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data that support the findings of this research will be available from the corresponding author M. Zeinhom upon reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes