NEW YORK (Reuters Health) – Giving uric acid (UA) before the end of alteplase infusion might limit early ischemic worsening (EIW) after a stroke in some patients, according to an exploratory analysis of data from the URICO-ICTUS trial.

URICO-ICTUS was a phase 2b/3 trial involving adults with acute ischemic stroke at 10 Spanish stroke centers. Patients were included if they had received alteplase within 4.5 hours of symptom onset and had a National Institutes of Health Stroke Scale score between 6 and 25 and premorbid modified Rankin Scale score of 2 or lower.

Patients were randomly allocated to receive uric acid 1000 mg or placebo IV during the infusion of alteplase. As it turned out, the addition of uric acid did not increase the proportion of patients who achieved the primary endpoint – an excellent outcome – according to a 2014 report of the study in Lancet Neurology.

More recently, in a tertiary analysis published online October 6 in Stroke, Dr. Angel Chamorro of Hospital Clinic de Barcelona and colleagues report that EIW occurred in 2 of 149 (1%) patients with good outcome and 23 of 262 (9%) patients with poor outcome (P=0.002). Furthermore, EIW occurred in 7 of 204 (3%) patients treated with UA and in 18 of 200 (9%) patients treated with placebo (P=0.01).

They defined EIW as an increase of at least 4 points in the National Institutes of Health Stroke Scale score within 72 hours of treatment in the absence of hemorrhage or recurrent stroke.

In a subgroup of 112 patients who had full assessment of the collateral circulation using advanced brain imaging, several traits predicted a higher incidence of EIW, but only the collateral score showed a significant interaction with the efficacy of UA therapy to prevent EIW, according to the research team.

The researchers concluded that although the URICO-ICTUS trial did not meet its primary goal, the new findings justify further study of UA therapy for acute ischemic stroke.

“Optimal access of UA to its molecular targets through appropriate collaterals may modify the magnitude of the neuroprotective effect,” they suggest.

In email to Reuters Health, Dr. Chamorro said, “Our results show that uric acid is a stroke extracellular antioxidant and this effect is of great clinical relevance as (shown in this paper) it successfully prevents worsening symptoms in the stroke population.”

Dr. Chamorro said he was not surprised by the results. “We specifically included as a predefined secondary outcome measure the treatment effect of uric acid versus placebo on the incidence of early ischemic worsening,” he said. “This was based on the amount of previous data indicating that worsening of acute stroke in the initial hours that follow the onset of symptoms may be sustained on oxidative stress mechanisms which are those targeted by our experimental approach.”

Dr. Chamorro noted that to change clinical practice, the findings would have to be confirmed in a pivotal trial. “In the meantime, uric acid is not available and it is not included in the current therapeutic guidelines of acute stroke. Overall, this manuscript stresses the urgency of replicating ASAP these very encouraging results,” he said.

In an email to Reuters Health, Dr. Larry Goldstein, a spokesperson for the American Stroke Association and codirector of the Kentucky Neuroscience Institute in Lexington, who was not involved with the study, said that while this analysis of a tertiary endpoint “does raise the possibility that combining uric acid with definitive clot removal (i.e., clot retrieval) might prove useful . . . this would need to be assessed in a prospective trial.”

The trial was funded by the Institute of Health Carlos III of the Spanish Ministry of Health, the Spanish Ministry of Economy and Competence, and the Fundacion Doctor Melchor Colet.