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

Sponsor

Angel Chamorro, MD (Other)

Overall Status

Completed

CT.gov ID

NCT00860366

Collaborator

Carlos III Health Institute (Other)

421

Enrollment

Locations

Arms

Duration (Months)

42.1

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

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 :

Jun 1, 2011

Actual Primary Completion Date :

Aug 1, 2013

Actual Study Completion Date :

Oct 1, 2013

Arms and Interventions

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.

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.

Outcome Measures

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 [90 days after the inclusion.]

Secondary Outcome Measures

Proportion of patients with NIHSS <2 at 2 hours after completing the experimental treatment. [2 hours after completing the experimental treatment]
Proportion of patients with NIHSS <1 at day 90. [Day 90]
Proportion of patients achieving a Barthel scale of 95 to 100 at day 90 [Day 90]
All-cause mortality within the first 90 days. [Day 90]
Final Infarction Volume measured by means of MRI or multimodal CT at 72 hours of onset (in specific centers) [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. [36 hours.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
2	Hospital Universitari de Bellvitge	Bellvitge	Barcelona	Spain
3	Corporació Sanitària del Parc Taulí	Sabadell	Barcelona	Spain	08208
4	Hospital Universitari Mútua de Terrassa	Terrassa	Barcelona	Spain	08221
5	Hospital de Navarra	Pamplona	Navarra	Spain	31008
6	Hospital General Universitario de Albacete	Albacete		Spain	02006
7	Hospital de la Santa Creu y Sant Pau	Barcelona		Spain	08025
8	Hospital Clínic de Barcelona	Barcelona		Spain	08036
9	Hospital Dr Josep Trueta	Girona		Spain	17007
10	Hospital Clínico Universitario de Valladolid	Valladolid		Spain	47005