Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke - Full Text View

Sponsor:	Fundacion Clinic per a la Recerca Biomédica
Collaborator:	Carlos III Health Institute
Information provided by:	Fundacion Clinic per a la Recerca Biomédica
ClinicalTrials.gov Identifier:	NCT00860366

Purpose

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	Intervention	Phase
Acute Ischemic Stroke	Drug: Uric Acid Other: Vehicle	Phase II Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Drug Information available for: Alteplase Tissue-type plasminogen activator Lithium carbonate Lithium citrate

U.S. FDA Resources

Further study details as provided by Fundacion Clinic per a la Recerca Biomédica:

Primary Outcome Measures:

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. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of patients with NIHSS <2 at 2 hours after completing the experimental treatment. [ Time Frame: 2 hours after completing the experimental treatment ] [ Designated as safety issue: No ]
Proportion of patients with NIHSS <1 at day 90. [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
Proportion of patients achieving a Barthel scale of 95 to 100 at day 90 [ Time Frame: Day 90 ] [ Designated as safety issue: No ]
All-cause mortality within the first 90 days. [ Time Frame: Day 90 ] [ Designated as safety issue: Yes ]
Final Infarction Volume measured by means of MRI or multimodal CT at 72 hours of onset (in specific centers) [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
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. ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	420
Study Start Date:	September 2009
Estimated Study Completion Date:	September 2012
Estimated Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860366

Contacts

Contact: Ángel Chamorro, MD, PhD.

+34 932275400 ext 2424

mvargas@clinic.ub.es

Locations

Spain
Corporació Sanitària del Parc Taulí	Not yet recruiting
Sabadell, Barcelona, Spain, 08208
Principal Investigator: David Cánovas, MD
Hospital de Navarra	Not yet recruiting
Pamplona, Navarra, Spain, 31008
Principal Investigator: Jaime Gállego, MD, PhD
Hospital General Universitario de Albacete	Not yet recruiting
Albacete, Spain, 02006
Principal Investigator: Tomás Segura, MD, PhD.
Hospital de la Santa Creu y Sant Pau	Not yet recruiting
Barcelona, Spain, 08025
Principal Investigator: Joan Martí-Fabregas, MD, PhD.
Hospital Clínic de Barcelona	Not yet recruiting
Barcelona, Spain, 08036
Contact: Angel Chamorro, MD, PhD. +34 932275400 ext 2414 mvargas@clinic.ub.es
Sub-Investigator: Victor Obach, MD
Sub-Investigator: Alvaro Cervera, MD, PhD.
Sub-Investigator: Sergio Amaro, MD
Sub-Investigator: Manuel Gomez-Choco, MD
Sub-Investigator: Xabier Urra, MD
Principal Investigator: Angel Chamorro, MD, PhD.
Hospital Dr Josep Trueta	Not yet recruiting
Girona, Spain, 17007
Principal Investigator: Mar Castellanos, MD, PhD

Sponsors and Collaborators

Fundacion Clinic per a la Recerca Biomédica

Carlos III Health Institute

Investigators

Study Director:

Angel Chamorro, MD, PhD.

Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain.

More Information

Publications:

Chamorro A, Obach V, Cervera A, Revilla M, Deulofeu R, Aponte JH. Prognostic significance of uric acid serum concentration in patients with acute ischemic stroke. Stroke. 2002 Apr;33(4):1048-52.

Chamorro A, Planas AM. Yin and yang of uric acid in patients with stroke. Stroke. 2004 Jan;35(1):e11-2; author reply e11-2. Epub 2003 Dec 11. No abstract available.

Chamorro A, Planas AM, Muner DS, Deulofeu R. Uric acid administration for neuroprotection in patients with acute brain ischemia. Med Hypotheses. 2004;62(2):173-6.

Romanos E, Planas AM, Amaro S, Chamorro A. Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab. 2007 Jan;27(1):14-20. Epub 2006 Apr 5.

Amaro S, Soy D, Obach V, Cervera A, Planas AM, Chamorro A. A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke. 2007 Jul;38(7):2173-5. Epub 2007 May 24.

Amaro S, Planas AM, Chamorro A. Uric acid administration in patients with acute stroke: a novel approach to neuroprotection. Expert Rev Neurother. 2008 Feb;8(2):259-70. Review.

Responsible Party:	Ángel Chamorro Sánchez; MD, PhD, Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain
ClinicalTrials.gov Identifier:	NCT00860366 History of Changes
Other Study ID Numbers:	URICOICTUS-1-2007, EudraCT 2007-002687-95, FIS EC07-90276
Study First Received:	March 11, 2009
Last Updated:	March 11, 2009
Health Authority:	Spain: Spanish Agency of Medicines

Keywords provided by Fundacion Clinic per a la Recerca Biomédica:

Acute ischemic stroke
thrombolysis
alteplase

uric acid
neuroprotection
oxidative stress

Additional relevant MeSH terms:

Ischemia
Stroke
Cerebral Infarction
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Uric Acid
Lithium Carbonate
Lithium

Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Enzyme Inhibitors
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Antipsychotic Agents

ClinicalTrials.gov processed this record on February 09, 2012