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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00860366
Recruitment Status : Completed
First Posted : March 12, 2009
Last Update Posted : March 10, 2015
Carlos III Health Institute
Information provided by (Responsible Party):
Angel Chamorro, MD, Fundacion Clinic per a la Recerca Biomédica

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Ischemic Stroke Drug: Uric Acid Other: Vehicle Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 421 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : October 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Uric Acid

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.

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Proportion of patients with NIHSS <2 at 2 hours after completing the experimental treatment. [ Time Frame: 2 hours after completing the experimental treatment ]
  2. Proportion of patients with NIHSS <1 at day 90. [ Time Frame: Day 90 ]
  3. Proportion of patients achieving a Barthel scale of 95 to 100 at day 90 [ Time Frame: Day 90 ]
  4. All-cause mortality within the first 90 days. [ Time Frame: Day 90 ]
  5. Final Infarction Volume measured by means of MRI or multimodal CT at 72 hours of onset (in specific centers) [ Time Frame: 72 hours ]
  6. 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. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00860366

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Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Universitari de Bellvitge
Bellvitge, Barcelona, Spain
Corporació Sanitària del Parc Taulí
Sabadell, Barcelona, Spain, 08208
Hospital Universitari Mútua de Terrassa
Terrassa, Barcelona, Spain, 08221
Hospital de Navarra
Pamplona, Navarra, Spain, 31008
Hospital General Universitario de Albacete
Albacete, Spain, 02006
Hospital de la Santa Creu y Sant Pau
Barcelona, Spain, 08025
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Hospital Dr Josep Trueta
Girona, Spain, 17007
Hospital Clínico Universitario de Valladolid
Valladolid, Spain, 47005
Sponsors and Collaborators
Angel Chamorro, MD
Carlos III Health Institute
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Study Director: Angel Chamorro, MD, PhD. Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain.


Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Angel Chamorro, MD, MD, PhD, Fundacion Clinic per a la Recerca Biomédica Identifier: NCT00860366     History of Changes
Other Study ID Numbers: URICOICTUS-1-2007
EudraCT 2007-002687-95
FIS EC07-90276
First Posted: March 12, 2009    Key Record Dates
Last Update Posted: March 10, 2015
Last Verified: March 2015

Keywords provided by Angel Chamorro, MD, Fundacion Clinic per a la Recerca Biomédica:
Acute ischemic stroke
uric acid
oxidative stress

Additional relevant MeSH terms:
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Cerebral Infarction
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia
Lithium Carbonate
Uric Acid
Antidepressive Agents
Psychotropic Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Diuretics, Osmotic
Natriuretic Agents
Protective Agents