Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke

Angel Chamorro, MD421 enrolled

Overview

The purpose of this study is to determine whether the combined treatment with Uric Acid and rtPA is superior to rtPA alone in terms of clinical efficacy in acute ischemic stroke patients treated within the first 4.5 hours of symptoms onset.

Oxidative stress is a major contributor to brain damage in patients with ischemic stroke. Uric acid (UA) is an endogenous product derived from the metabolism of purins which in man is responsable of the 60% of the total antioxidant capacity of the organism. Recent experimental evidences gathered by our and other research groups have shown that the exogenous administration of UA is neuroprotective both in cortical and subcortical brain areas as the result of its antioxidant properties. In these studies, animals treated with UA disclosed smaller brain infarction after transient focal ischemia, both using the intraluminal model or after the injection of autologous clots. Moreover, our group first described greater neuroprotection in animals pretreated with rtPA (alteplase). Likewise, we have recently shown that the administration of UA was free of serious adverse effects in stroke patients receiving rtPA within 3 hours of stroke onset. Yet, preliminary data suggested that this intervention might translate into clinical benefits at 3 months follow-up. Based on these data, we aim to conduct a phase 3, randomized, double-blind, controlled trial assessing the clinical efficacy of UA administration in acute ischemic stroke patients. Currently, rtPA is the only approved therapy for stroke patients within the first hours of clinical onset, and oxidative stress is thought particularly relevant following ischemia/reperfusion. Based on this ground, we aim to conduct this phase 3 clinical trial in ischemic stroke patients which are currently treated with rtPA within the 4'5 hour window.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

421

Conditions

Acute Ischemic Stroke

Interventions

Uric AcidDRUG

1 gram dissolved in a vehicle containing 500 ml of 0'1% Lithium Carbonate and 5% Mannitol, IV (in the vein), single dose.

VehicleOTHER

Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion criteria: * Age older than 18 years old. * Acute ischemic stroke treated with rtPA within the first 4.5 hours of clinical onset. Baseline National Institute of Health Stroke Scale (NIHSS) \>6 and \<25, and modified Rankin Scale (mRS) of 2 prior to the stroke. * Cranial CT disclosing the absence of blood in the CNS. * Informed consent. Exclusion criteria: * Presence of any of the valid exclusion criteria for the administration of rtPA in the current clinical practise. * History of gout with or without history of gouty nephropathy, or uric lithiasis. Asymptomatic hiperuricemia under chronic treatment with allopurinol, or chronic treatment with lithium. * Chronic renal insufficiency (baseline creatinine \> 1,5mg/dl).

Locations (10)

Hospital General Universitario de Albacete

Albacete, Albacete, Spain

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital de la Santa Creu y Sant Pau

Barcelona, Barcelona, Spain

Outcomes

Primary Outcomes

Proportion of patients achieving a mRS of 0 to 1 at 3 months after treatment, or 2 in those patients with a mRS 2 prior to the inclusion in the study

Time frame: 90 days after the inclusion.

Secondary Outcomes

Proportion of patients with NIHSS <2 at 2 hours after completing the experimental treatment.

Time frame: 2 hours after completing the experimental treatment

Proportion of patients with NIHSS <1 at day 90.

Time frame: Day 90

Proportion of patients achieving a Barthel scale of 95 to 100 at day 90

Time frame: Day 90

All-cause mortality within the first 90 days.

Time frame: Day 90

Final Infarction Volume measured by means of MRI or multimodal CT at 72 hours of onset (in specific centers)

Time frame: 72 hours

Proportion of patients with an intracranial hemorrhage associated to a worsening of 4 points in the NIHSS within the first 36 hours of treatment.

Time frame: 36 hours.

Data from ClinicalTrials.gov

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