Relevance of Collaterals for the Success of Neuroprotective Therapies in Acute Ischemic Stroke: Insights from the Randomized URICO-ICTUS Trial.
Aged
Aged, 80 and over
Brain Ischemia
/ diagnostic imaging
Cerebrovascular Circulation
Collateral Circulation
Double-Blind Method
Drug Administration Schedule
Female
Fibrinolytic Agents
/ administration & dosage
Humans
Infusions, Intravenous
Male
Middle Aged
Neuroprotective Agents
/ administration & dosage
Recovery of Function
Spain
Stroke
/ diagnostic imaging
Thrombolytic Therapy
/ adverse effects
Time Factors
Tissue Plasminogen Activator
/ administration & dosage
Treatment Outcome
Uric Acid
/ administration & dosage
Collaterals
Ischemic stroke
Neuroprotection
Uric acid
Journal
Cerebrovascular diseases (Basel, Switzerland)
ISSN: 1421-9786
Titre abrégé: Cerebrovasc Dis
Pays: Switzerland
ID NLM: 9100851
Informations de publication
Date de publication:
2019
2019
Historique:
received:
03
02
2019
accepted:
01
05
2019
pubmed:
5
6
2019
medline:
26
2
2020
entrez:
5
6
2019
Statut:
ppublish
Résumé
Collateral circulation may modify the effect of neuroprotective therapies. We report a post hoc analysis of the URICO-ICTUS trial (NCT00860366) assessing the modifying treatment effect of pretreatment collaterals on clinical and radiological outcomes in patients with large-vessel acute ischemic stroke receiving uric acid therapy or placebo. URICO-ICTUS was a randomized clinical trial where 411 alteplase-treated patients also received uric acid 1,000 mg (n = 211) or placebo (n = 200) before the end of alteplase infusion. Herein, we included a nested study of 84 patients (placebo = 40, uric acid = 44) who had a pretreatment CT-angiography (CTA) showing a proximal arterial occlusion in the carotid territory. Excellent collaterals were defined as 100% collateral supply on pretreatment CTA. Regression models assessed the interaction between therapy (uric acid/placebo) and collaterals on the main outcome (ordinal modified Rankin Scale [mRS] shift at 90 days). Overall, excellent collaterals were associated with improved outcome. There was a significant interaction between therapy and pretreatment collaterals (p interaction = 0.02) for the prediction of improved mRS shift. The largest treatment contrast in favor of uric acid was found in patients with excellent collaterals (adjusted OR 9.2; 95% CI 1.23-68.6; p = 0.03). Collectively, the study found that collaterals were associated with the neuroprotective effect of uric acid therapy highlighting the importance of assessing collateral status in neuroprotection trials.
Sections du résumé
BACKGROUND
Collateral circulation may modify the effect of neuroprotective therapies. We report a post hoc analysis of the URICO-ICTUS trial (NCT00860366) assessing the modifying treatment effect of pretreatment collaterals on clinical and radiological outcomes in patients with large-vessel acute ischemic stroke receiving uric acid therapy or placebo.
METHODS
URICO-ICTUS was a randomized clinical trial where 411 alteplase-treated patients also received uric acid 1,000 mg (n = 211) or placebo (n = 200) before the end of alteplase infusion. Herein, we included a nested study of 84 patients (placebo = 40, uric acid = 44) who had a pretreatment CT-angiography (CTA) showing a proximal arterial occlusion in the carotid territory. Excellent collaterals were defined as 100% collateral supply on pretreatment CTA. Regression models assessed the interaction between therapy (uric acid/placebo) and collaterals on the main outcome (ordinal modified Rankin Scale [mRS] shift at 90 days).
RESULTS
Overall, excellent collaterals were associated with improved outcome. There was a significant interaction between therapy and pretreatment collaterals (p interaction = 0.02) for the prediction of improved mRS shift. The largest treatment contrast in favor of uric acid was found in patients with excellent collaterals (adjusted OR 9.2; 95% CI 1.23-68.6; p = 0.03).
CONCLUSIONS
Collectively, the study found that collaterals were associated with the neuroprotective effect of uric acid therapy highlighting the importance of assessing collateral status in neuroprotection trials.
Identifiants
pubmed: 31163434
pii: 000500712
doi: 10.1159/000500712
doi:
Substances chimiques
Fibrinolytic Agents
0
Neuroprotective Agents
0
Uric Acid
268B43MJ25
Tissue Plasminogen Activator
EC 3.4.21.68
Banques de données
ClinicalTrials.gov
['NCT00860366']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
171-177Informations de copyright
© 2019 S. Karger AG, Basel.