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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Monica Millan Torne, Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier:
NCT00777140
First received: October 21, 2008
Last updated: July 4, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Acute Ischemic Stroke
Drug: Deferoxamine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Germans Trias i Pujol Hospital:

Primary Outcome Measures:
  • Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan. [ Time Frame: 24h, 7days and 3 months ] [ Designated as safety issue: No ]
  • Deferoxamine and ferritin levels in serum (pharmacokinetics). [ Time Frame: 72h ] [ Designated as safety issue: Yes ]

Enrollment: 62
Study Start Date: September 2008
Study Completion Date: December 2011
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1. Deferoxamine
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.
Drug: Deferoxamine

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.

Placebo Comparator: 2. Placebo
Saline solution: Bolus and perfusion during 72h. 5 patients in the placebo arm in each step (randomization 3:1)
Drug: Deferoxamine

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.


  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00777140

Locations
Spain
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain, 08916
Hospital Clínico Universitario de Santiago de Compostela
Santiago de Compostela, La Coruña, Galicia, Spain, 15706
Hospital Universitari Josep Trueta
Girona, Spain, 17007
Hospital Universitario de la Princesa
Madrid, Spain, 28006
Sponsors and Collaborators
Germans Trias i Pujol Hospital
Investigators
Principal Investigator: Monica Millán Torné, MD Germans Trias i Pujol Hospital
  More Information

Publications:

Responsible Party: Monica Millan Torne, Medical Doctor, Germans Trias i Pujol Hospital
ClinicalTrials.gov Identifier: NCT00777140     History of Changes
Other Study ID Numbers: TANDEM-1, EUDRACT: 2007-006731-31
Study First Received: October 21, 2008
Last Updated: July 4, 2012
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)

Keywords provided by Germans Trias i Pujol Hospital:
Stroke
Ischemic Stroke
Thrombolytic treatment
Middle cerebral artery occlusion
Deferoxamine
Iron chelator
Acute Ischemic Stroke treated with Intravenous Thrombolytic

Additional relevant MeSH terms:
Cerebral Arterial Diseases
Cerebral Infarction
Infarction, Middle Cerebral Artery
Ischemia
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Arterial Diseases
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Deferoxamine
Fibrinolytic Agents
Tissue Plasminogen Activator
Cardiovascular Agents
Chelating Agents
Fibrin Modulating Agents
Hematologic Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents
Siderophores
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014