Clinical trial NCT06210646: Citicoline in Ischemic Stroke, a Randomized Trial
Official title: Citicoline in Ischemic Stroke, a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ischemic Stroke
Keywords: citicoline
ischemic stroke
Egypt
Lead sponsor: Kafrelsheikh University
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: We will conduct our randomized controlled trial, which will contain 2 arms: the citicoline arm, which consists of 400 patients who received 2000 mg citicoline once daily for 12 months, and the placebo arm, consisting of 400 patients who received 1000 mg citicoline once daily for 12 months; both groups will receive 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.
Primary purpose: TREATMENT

Brief summary: Along with the current clinical trial, the efficacy and safety of a 2000 mg daily citicoline administered within 24 hours of the first-ever ischemic stroke and lasted 12 months compared to 1000 mg were assessed through MoCA, NIHSS, mRS, and possible adverse effects.

Detailed description: The investigators conducted a single-blinded, placebo-controlled, randomized controlled trial between December 2022 and June 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 2000 mg citicoline once daily for 12 months, and the placebo arm, consisting of 400 patients who received 1000 mg citicoline 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 \&amp; 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 \&amp; 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 \&amp; Lipid Profile\&amp; 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Value of Montreal Cognitive Assessment (MoCA)
timeFrame: 6 months
measure: Rate of drug-related complications after 6 months
timeFrame: 6 months
Secondary outcomes:
measure: Value of Montreal Cognitive Assessment (MoCA)
timeFrame: 12 months
measure: Value of Modified Rankin Scale (mRS) at 6 months
timeFrame: 6 months
measure: Value of Modified Rankin Scale (mRS) at 12 months
timeFrame: 12 months
measure: Rate of drug-related complications after 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Kafr Ash Shaykh
country: Egypt
facility: Kafr Elsheikh University Hospital
Study officials:
affiliation: neurology department kafr el-sheikh university
name: mohamed G. Zeinhom, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.