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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Carlos III Health Institute
Information provided by (Responsible Party):
Angel Chamorro, MD, Fundació Clínic per la Recerca Biomèdica
ClinicalTrials.gov Identifier:
NCT00860366
First received: March 11, 2009
Last updated: September 30, 2013
Last verified: September 2013

March 11, 2009
September 30, 2013
June 2011
August 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00860366 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Efficacy Study of Combined Treatment With Uric Acid and rtPA in Acute Ischemic Stroke
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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Acute Ischemic Stroke
  • 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.
  • Other: Vehicle
    Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.
  • 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).
    Intervention: Drug: Uric Acid
  • Placebo Comparator: Vehicle
    Single intravenous infusion of a 500 ml vehicle containing 0'1% Lithium Carbonate and 5% Mannitol.
    Intervention: Other: Vehicle

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
420
October 2013
August 2013   (final data collection date for primary outcome measure)

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).
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT00860366
URICOICTUS-1-2007, EudraCT 2007-002687-95, FIS EC07-90276
Yes
Angel Chamorro, MD, Fundació Clínic per la Recerca Biomèdica
Angel Chamorro, MD
Carlos III Health Institute
Study Director: Angel Chamorro, MD, PhD. Comprehensive Stroke Center, Hospital Clínic Barcelona, Spain.
Fundacion Clinic per a la Recerca Biomédica
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP