Clinical trial NCT00777140: Thrombolysis and Deferoxamine in Middle Cerebral Artery Occlusion
Official title: Double-blind, Randomized, Placebo Controlled, Dose-finding Phase 2 Clinical Trial of Intravenous Deferoxamine in Patients With Acute Ischemic Stroke Treated With Tissue Plasminogen Activator
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemic Stroke, Acute
Keywords: Stroke
Ischemic Stroke
Thrombolytic treatment
Middle cerebral artery occlusion
Deferoxamine
Iron chelator
Acute Ischemic Stroke treated with Intravenous Thrombolytic
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundació Institut Germans Trias i Pujol
First posted: 2008-10-22
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events)
timeFrame: 3 months
Secondary outcomes:
measure: Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan.
timeFrame: 24h, 7days and 3 months
measure: Deferoxamine and ferritin levels in serum (pharmacokinetics).
timeFrame: 72h
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
state: La Coruña, Galicia
city: Girona
country: Spain
facility: Hospital Universitari Josep Trueta
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
Study officials:
affiliation: Germans Trias i Pujol Hospital
name: Monica Millán Torné, MD
role: PRINCIPAL_INVESTIGATOR
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