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

August 4, 2022 updated by: Monica Millan Torne, Germans Trias i Pujol Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

62

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Girona, Spain, 17007
        • Hospital Universitari Josep Trueta
      • Madrid, Spain, 28006
        • Hospital Universitario de la Princesa
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitari Germans Trias i Pujol
    • La Coruña, Galicia
      • Santiago de Compostela, La Coruña, Galicia, Spain, 15706
        • Hospital Clinico Universitario de Santiago de Compostela

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events)
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan.
Time Frame: 24h, 7days and 3 months
24h, 7days and 3 months
Deferoxamine and ferritin levels in serum (pharmacokinetics).
Time Frame: 72h
72h

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Germans Trias i Pujol Hospital

Collaborators

Fundació Institut Germans Trias i Pujol

Investigators

  • Principal Investigator: Monica Millán Torné, MD, Germans Trias I Pujol Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ACTUAL)

December 1, 2011

Study Completion (ACTUAL)

December 1, 2011

Study Registration Dates

First Submitted

October 21, 2008

First Submitted That Met QC Criteria

October 21, 2008

First Posted (ESTIMATE)

October 22, 2008

Study Record Updates

Last Update Posted (ACTUAL)

August 8, 2022

Last Update Submitted That Met QC Criteria

August 4, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TANDEM-1
  • EUDRACT: 2007-006731-31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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