Ischemic Stroke, Acute
Conditions
Keywords
Stroke, Ischemic Stroke, Thrombolytic treatment, Middle cerebral artery occlusion, Deferoxamine, Iron chelator, Acute Ischemic Stroke treated with Intravenous Thrombolytic
Brief summary
Iron overload has been associated with greater brain injury in ischemia/reperfusion experimental stroke models and ischemic stroke patients, especially in those treated with thrombolytic treatment. Deferoxamine administration, an iron chelator, offers a neuroprotective action in ischemia/reperfusion animal models. Primary objective: To evaluate the security and tolerability of deferoxamine endovenous treatment in acute ischemic stroke patients treated with iv. tPA. Secondary objectives: To study pharmacokinetics of deferoxamine given by endovenous bolus (10 mg/Kg) followed by 72-hour continuous intravenous infusion (20, 40 o 60 mg/Kg). To evaluate the deferoxamine effect in clinical outcome, infarct volume and hemorrhagic transformation and brain edema development. Methodology: Double-blind, randomized, placebo controlled, dose-finding phase II clinical trial. Study stages: 1st: bolus+20 mg/Kg/day vs. Placebo (n=15:5); 2nd: bolus+40 mg/Kg/day vs. Placebo (n=15:5); 3rd: bolus+60 mg/Kg/day vs placebo (n=15:5). These doses will be increased according to security results of the previous stage. Patients will be continuously monitored in stroke units. Laboratory parameters will be measured at baseline, 24h, 72h and 30 days to evaluate adverse events related to the drug. Serum deferoxamine and feroxamine concentrations will be measured along time after the injection in a subgroup of patients to the pharmacokinetics study. CT scan will be performed at 24-36h to assess hemorrhagic transformation and brain edema. The NIH Stroke Scale will be evaluated during hospitalization, and the Rankin score at discharge and 3 months. If deferoxamine demonstrate to be secure and well tolerated treatment in acute stroke patients, it may be a new therapy option to lower the brain injury after ischemia and reperfusion.
Interventions
DRUGDeferoxamine
Intravenous deferoxamine: bolus 10mg/Kg (initiated during thrombolytic infusion, iv tPA), followed by intravenous perfusion of 20/40/60mg/Kg during 72h. It's a dose-finding study with 3 different doses of deferoxamine, with 20 patients (15 active:5 placebo) in each step. Bolus + 72h perfusion of saline solution for the placebo group.
Sponsors
Fundació Institut Germans Trias i Pujol
Germans Trias i Pujol Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-80 years old * Acute Ischemic Stroke on the middle cerebral artery territory * Treatment with iv tPA in the first 3 hours from symptoms onset
Exclusion criteria
* Modified Rankin Scale more or equal to 2 * Infectious, inflammatory, neoplastic or hematologic disease * Anemia (Hto\<34% or Hb\<10g/dl) * Previous renal failure * Previous treatment with oral iron supplement * Minor stroke (NIHSS less than 4), lacunar or posterior territory * Alcohol consumption (more than 40mg/Kg) * Pregnancy * Participation in other clinical trials
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events) | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan. | 24h, 7days and 3 months |
| Deferoxamine and ferritin levels in serum (pharmacokinetics). | 72h |
Countries
Spain
Outcome results
None listed