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

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ClinicalTrials.gov Identifier: NCT00777140
Recruitment Status : Completed
First Posted : October 22, 2008
Last Update Posted : July 6, 2012
Sponsor:
Collaborator:
Fundació Institut Germans Trias i Pujol
Information provided by (Responsible Party):
Monica Millan Torne, Germans Trias i Pujol Hospital

Tracking Information
First Submitted Date  ICMJE October 21, 2008
First Posted Date  ICMJE October 22, 2008
Last Update Posted Date July 6, 2012
Study Start Date  ICMJE September 2008
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 21, 2008)
Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events) [ Time Frame: 3 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 21, 2008)
  • Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan. [ Time Frame: 24h, 7days and 3 months ]
  • Deferoxamine and ferritin levels in serum (pharmacokinetics). [ Time Frame: 72h ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Thrombolysis and Deferoxamine in Middle Cerebral Artery Occlusion
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Acute Ischemic Stroke
Intervention  ICMJE 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.

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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 4, 2012)
62
Original Estimated Enrollment  ICMJE
 (submitted: October 21, 2008)
60
Actual Study Completion Date  ICMJE December 2011
Actual Primary Completion Date December 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00777140
Other Study ID Numbers  ICMJE TANDEM-1
EUDRACT: 2007-006731-31
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Monica Millan Torne, Germans Trias i Pujol Hospital
Study Sponsor  ICMJE Germans Trias i Pujol Hospital
Collaborators  ICMJE Fundació Institut Germans Trias i Pujol
Investigators  ICMJE
Principal Investigator: Monica Millán Torné, MD Germans Trias i Pujol Hospital
PRS Account Germans Trias i Pujol Hospital
Verification Date July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP