Clinical trial NCT05154903: Citicoline in Ischemic Stroke
Official title: Citicoline in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Keywords: citicoline
Egypt
ischemic stroke
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Kafrelsheikh University
First posted: 2021-12-13
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Prospective Randomized Open label trial with Blinded Evaluators, Citicoline will be administered in continuous iv infusion in a dose of 2000 mg per day for the first week following AIS then by oral route for the next 5 weeks.

The number of patients needed for this proposal is 200 (100 per group): group 1 (citicoline) : receiving citicoline and group 2 (control) not receiving citicoline. A 10% increase will be expected to avoid possible drop-outs.
Primary purpose: TREATMENT

Brief summary: There is evidence that citicoline is the only neuroprotectant able to improve the functional status of the patients after an acute ischemic stroke.

Citicoline is a neuroprotectant drug against cerebral ischemia, with positive results, both in experimental and clinical trials, in the treatment of acute stroke and head injuries

Also, the safety profile of citicoline is good, and there are no associated problems when the drug is used in this kind to patients

The aim of this study is to confirm the efficacy and safety of citicoline in patients with moderate-to-severe acute ischemic stroke in Egypt, according to the characteristics of the medical care in this country

Detailed description: This is a Prospective Randomized Open-label trial with Blinded Evaluators, Citicoline will be administered in continuous Iv infusion in a dose of 2000 mg per day for the first week following AIS then by oral route for the next 5 weeks.

The number of patients needed for this proposal is 200 (100 per group): group 1 (citicoline): receiving citicoline and group 2 (control) not receiving citicoline. A 10% increase will be expected to avoid possible drop-outs.

Assessment scales:

Eligibility scale: NIHSS score ≥ 8. Outcome scales: modified Rankin Score (mRS) at 3 months Cutoff scores for mRS will be 0-2 as a cut-off point for a good outcome and 3-6 for a bad outcome.

Also, a record of all the side effects will be done. Any kind of adverse effect must be recorded by filling the CIOMS form.

Randomization: computer-generated randomization to either group.

Eligibility criteria: Inclusion Criteria:

* - Both genders aged \> 18 years.
* Patients must be treated within 24 hours of their initial stroke symptoms onset.
* Patients not eligible to receive rTPA.
* Patients with a measurable focal neurological deficit (NIHSS score ≥ 8) lasting for a minimum of 60 minutes. This deficit must persist from onset and up to the time of treatment without clinically significant improvement
* Patients must have a CT scan and/or conventional MRI compatible with the clinical diagnosis of acute ischemic stroke prior to being randomized.
* Patients must have an acute ischemic stroke with symptoms referrable to internal carotid territory.
* At inclusion, NIHSS score 8-15, with at least 2 of these points from sections 5 \& 6 (motor).
* Immediately (i.e. minutes) pre-stroke, mRS ≤ 1. \[History of past stroke does not, by itself, preclude study entrance\].
* Women of childbearing potential must have a negative pregnancy test prior to enrolment.
* Signed informed consent (following a full explanation of the nature and purpose of this study, the patient or legal guardian(s) or representative(s) must consent to participate by signing the Informed Consent document

Exclusion Criteria:

* Patients eligible for rTPA treatment.
* Patients in coma: patients having a score of 2 or higher in the items regarding the level of consciousness in the NIHSS (1a).
* CT or conventional MRI evidence of any structural brain disorder other than ischemic stroke.
* History of ventricular dysrhythmias, acute myocardial infarction within 72 hours prior to 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 an score of 2 or higher in the previous mRS.
* Pre-existing medical condition that, in the Investigator's opinion, may interfere with the patient's suitability and participation in the study.
* Patients participating in another clinical trial or receiving a non-approved drug (clinical investigational drug) less than 30 days prior to screening.
* Patients under current treatment with citicoline.
* Prior (over past 3 months) or concomitant administration of other neuroprotectant drugs (such as nimodipine, vinponcetine, piracetam, cerebrolysin,...).

Primary outcomes:
measure: percentage of patients with a good outcome using modified Rankin scale
timeFrame: 3 months
Secondary outcomes:
measure: Incidence of Citicoline-Emergent Adverse Events
timeFrame: 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University
Study officials:
References:
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: Alvarez-Sabin J, Roman GC. The role of citicoline in neuroprotection and neurorepair in ischemic stroke. Brain Sci. 2013 Sep 23;3(3):1395-414. doi: 10.3390/brainsci3031395.
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.