PDF: CAISR
(2022)Objective
To determine if Citicoline administered immediately after recanalization therapy for acute ischemic stroke improves clinical or radiological outcomes.
Study Summary
• Citicoline showed no significant benefit over placebo in infarct volume reduction or functional outcomes after acute ischemic stroke treated with reperfusion therapy
• The trial was stopped prematurely due to the COVID-19 pandemic before reaching its target enrollment, making it underpowered.
• Patients were randomized to a 6-week course of the neuroprotectant Citicoline or a placebo.
• There was no significant difference in the primary outcome of infarct volume change at 6 weeks, or in secondary clinical outcomes like modified Rankin Scale (mRS) or NIHSS scores at 90 days.
• The trial was stopped prematurely due to the COVID-19 pandemic before reaching its target enrollment, making it underpowered.
• Patients were randomized to a 6-week course of the neuroprotectant Citicoline or a placebo.
• There was no significant difference in the primary outcome of infarct volume change at 6 weeks, or in secondary clinical outcomes like modified Rankin Scale (mRS) or NIHSS scores at 90 days.
Intervention
A 6-week course of Citicoline (1g twice daily; administered intravenously for 3 days then orally) or placebo, initiated immediately after recanalization therapy for acute ischemic stroke.
Study Design
Arms: Array
Outcome
• The primary outcome, change in infarct volume at 6 weeks, was not significantly different between groups (median decrease of 4.2 cm³ with Citicoline vs. 2.6 cm³ with placebo; p=0.483).
• Secondary clinical outcomes were also similar, with 65.3% of the Citicoline group and 62% of the placebo group achieving a favorable mRS score of 0-2 at 90 days (not significant).
• The trial found no evidence of benefit for Citicoline in this setting.
• Secondary clinical outcomes were also similar, with 65.3% of the Citicoline group and 62% of the placebo group achieving a favorable mRS score of 0-2 at 90 days (not significant).
• The trial found no evidence of benefit for Citicoline in this setting.
Bottom Line
In this single-center trial that was stopped prematurely, adjunctive Citicoline administered immediately after recanalization therapy did not result in a significant difference in the primary radiological outcome (change in stroke volume at 6 weeks) or in secondary clinical outcomes at 3 months compared to placebo.
Major Points
- CAISR was a single-center, randomized, placebo-controlled trial with blinded endpoint assessment conducted in India.
- The trial enrolled 99 patients with acute ischemic stroke who had undergone recanalization therapy with either intravenous thrombolysis, endovascular thrombectomy, or both.
- Patients were randomized 1:1 to receive a 6-week course of Citicoline (1g twice daily, starting with IV) or a matching placebo protocol.
- The primary outcome was the change in stroke infarct volume on MRI from baseline to 6 weeks.
- The trial was terminated prematurely due to the COVID-19 pandemic and failed to reach its target sample size, making it underpowered.
- No significant difference was found between the Citicoline and placebo groups for the primary outcome of infarct volume change or for any secondary clinical outcomes, including modified Rankin Scale (mRS) score, NIHSS score, or Barthel Index at 3 months.
Study Design
- Study Type
- Single-center, randomized, placebo-controlled, parallel-group trial with blinded endpoint assessment
- Randomization
- Yes
- Blinding
- Blinded endpoint assessment. Outcome assessors and radiologists were masked to treatment allocation.
- Sample Size
- 99
- Follow-up
- 3 months for clinical outcomes, 6 weeks for radiological outcome
- Centers
- 1
- Countries
- India
Primary Outcome
Definition: Change in stroke volume on MRI from baseline to 6 weeks after stroke onset.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Median decrease of 2.6 cm³ | Median decrease of 4.2 cm³ | - | 0.483 |
Limitations & Criticisms
- The study was stopped prematurely due to the COVID-19 pandemic and failed to reach its target sample size of 116 patients, making it underpowered to detect a true difference.
- A large number of enrolled patients (34 out of 99) were not included in the primary radiological outcome analysis due to death or inability to attend the follow-up MRI.
- The study was conducted at a single center, which may limit the generalizability of the findings.
- The baseline NIHSS was numerically lower and the onset-to-treatment time was longer in the placebo group, although these differences were not statistically significant.
Citation
PLOS ONE 17(5): e0269224.