Thrombolysis and Deferoxamine in Middle Cerebral Artery Occlusion (TANDEM-1)

Germans Trias i Pujol Hospital

Status and phase: Completed; Phase 2

Conditions: Ischemic Stroke, Acute

Treatments: Drug: Deferoxamine

Study type: Interventional

Funder types: Other

Identifiers

NCT00777140

TANDEM-1

EUDRACT: 2007-006731-31

Details and patient eligibility

About

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.

Enrollment: 62 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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62 participants in 2 patient groups, including a placebo group

1. Deferoxamine

Active Comparator group

Description:

Intravenous deferoxamine: bolus of 10mg/Kg (initiated during tPA infusion) and perfusion of 20/40/60 mg/Kg/day during 72h. Three different doses (3 steps), 15 patient in the active arm for each dose.

Treatment:

Drug: Deferoxamine

2. Placebo

Placebo Comparator group

Description:

Saline solution: Bolus and perfusion during 72h. 5 patients in the placebo arm in each step (randomization 3:1)

Treatment:

Drug: Deferoxamine