Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (Urico-Ictus)

March 9, 2015 updated by: Angel Chamorro, MD

Randomized, Double Blind Study Assessing the Clinical Efficacy of Combined Treatment With Uric Acid and rtPA Administered Intravenously in Acute Ischemic Stroke Patients Within the First 4.5 Hours of Symptoms Onset

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

421

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Albacete, Spain, 02006
        • Hospital General Universitario de Albacete
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu y Sant Pau
      • Girona, Spain, 17007
        • Hospital Dr Josep Trueta
      • Valladolid, Spain, 47005
        • Hospital Clínico Universitario de Valladolid
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
      • Bellvitge, Barcelona, Spain
        • Hospital Universitari de Bellvitge
      • Sabadell, Barcelona, Spain, 08208
        • Corporació Sanitària del Parc Taulí
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Universitari Mútua de Terrassa
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Hospital de Navarra

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Uric Acid
Single intravenous infusion of 1 gram of Uric Acid dissolved in vehicle (500 ml of 0'1% Lithium Carbonate and 5% Mannitol).
Drug: Uric Acid
1 gram dissolved in a vehicle containing 500 ml of 0'1% Lithium Carbonate and 5% Mannitol, IV (in the vein), single dose.
Placebo Comparator: Vehicle
Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.
Other: Vehicle
Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
90 days after the inclusion.

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion of patients with NIHSS <2 at 2 hours after completing the experimental treatment.
Time Frame: 2 hours after completing the experimental treatment
2 hours after completing the experimental treatment
Proportion of patients with NIHSS <1 at day 90.
Time Frame: Day 90
Day 90
Proportion of patients achieving a Barthel scale of 95 to 100 at day 90
Time Frame: Day 90
Day 90
All-cause mortality within the first 90 days.
Time Frame: Day 90
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
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.
36 hours.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Angel Chamorro, MD

Collaborators

Carlos III Health Institute

Investigators

  • Study Director: Angel Chamorro, MD, PhD., Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

October 1, 2013

Study Registration Dates

First Submitted

March 11, 2009

First Submitted That Met QC Criteria

March 11, 2009

First Posted (Estimate)

March 12, 2009

Study Record Updates

Last Update Posted (Estimate)

March 10, 2015

Last Update Submitted That Met QC Criteria

March 9, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • URICOICTUS-1-2007
  • EudraCT 2007-002687-95
  • FIS EC07-90276

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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