Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (Urico-Ictus)
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| ClinicalTrials.gov Identifier: NCT00860366 |
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Recruitment Status
:
Completed
First Posted
: March 12, 2009
Last Update Posted
: March 10, 2015
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Sponsor:
Angel Chamorro, MD
Collaborator:
Carlos III Health Institute
Information provided by (Responsible Party):
Angel Chamorro, MD, Fundació Clínic per la Recerca Biomèdica
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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 |
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 (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
U.S. FDA Resources
| Arm | Intervention/treatment |
|---|---|
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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).
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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.
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Placebo Comparator: Vehicle
Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.
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Other: Vehicle
Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.
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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. ]
Secondary Outcome Measures
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- 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. ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| 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).
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 ClinicalTrials.gov identifier (NCT number): NCT00860366
Locations
| Spain | |
| 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
Investigators
| Study Director: | Angel Chamorro, MD, PhD. | Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain. |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Angel Chamorro, MD, MD, PhD, Fundació Clínic per la Recerca Biomèdica |
| ClinicalTrials.gov 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, Fundació Clínic per la Recerca Biomèdica:
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Acute ischemic stroke thrombolysis alteplase |
uric acid neuroprotection oxidative stress |
Additional relevant MeSH terms:
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Stroke Ischemia 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 Mannitol |
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 Diuretics Natriuretic Agents Antioxidants Protective Agents |