Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke (Urico-Ictus)
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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 2 Phase 3 |
| 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 |
- 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 ]
- 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: | June 2011 |
| Estimated Study Completion Date: | October 2013 |
| Primary Completion Date: | August 2013 (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 |
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 LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00860366
| 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 Clínic de Barcelona | |
| Barcelona, Spain, 08036 | |
| Hospital de la Santa Creu y Sant Pau | |
| Barcelona, Spain, 08025 | |
| Hospital Dr Josep Trueta | |
| Girona, Spain, 17007 | |
| Hospital Clínico Universitario de Valladolid | |
| Valladolid, Spain, 47005 | |
| Study Director: | Angel Chamorro, MD, PhD. | Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain. |
More Information
Publications:
| 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 |
| Study First Received: | March 11, 2009 |
| Last Updated: | September 30, 2013 |
| 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:
|
Stroke Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Nervous System Diseases Vascular Diseases Lithium Lithium Carbonate Uric Acid Antidepressive Agents Antimanic Agents |
Antioxidants Antipsychotic Agents Central Nervous System Agents Central Nervous System Depressants Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs Protective Agents Psychotropic Drugs Therapeutic Uses Tranquilizing Agents |
ClinicalTrials.gov processed this record on March 03, 2015