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Ischemic Stroke, AcutePhase 2TANDEM-1NCT00777140

Thrombolysis and Deferoxamine in Middle Cerebral Artery Occlusion

A Phase 2 study testing Deferoxamine in people with Ischemic Stroke, Acute, run by Germans Trias i Pujol Hospital at 4 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Ischemic Stroke, Acute
What is being tested?
Deferoxamine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
62 participants
Where
4 sitesSpain
Study dates
Sep 2008to Dec 2011
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 9Show fewer
  • Alcohol consumption (more than 40mg/Kg)
  • Pregnancy
  • Participation in other clinical trials

Trial locations and contacts

4 sites in 1 country.

Spain4 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital Universitari Josep Trueta

    Girona, 17007

  • Hospital Universitario de la Princesa

    Madrid, 28006

  • Hospital Clínico Universitario de Santiago de Compostela

    Santiago de Compostela, La Coruña, Galicia, 15706

Other trials in Spain

About this study

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

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.

Read more

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.

Being tested
Deferoxamine
Keywords
Stroke, Ischemic Stroke, Thrombolytic treatment, Middle cerebral artery occlusion, Deferoxamine, Iron chelator, Acute Ischemic Stroke treated with Intravenous Thrombolytic
Medical subject headings
Ischemic Stroke, Stroke, Infarction, Middle Cerebral Artery

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DeferoxamineDrug

    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 groups in NCT00777140
Study groupRoleWhat they receive
1. DeferoxamineActive comparatorIntravenous 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.
Receives: Drug: Deferoxamine
2. PlaceboPlacebo comparatorSaline solution: Bolus and perfusion during 72h. 5 patients in the placebo arm in each step (randomization 3:1)
Receives: Drug: Deferoxamine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events)

    Measured: 3 months

Secondary outcomes (2)

  1. Neurological status (NIHSS, Barthel and Rankin scales), final ischemic lesion volume on CTscan.

    Measured: 24h, 7days and 3 months

  2. Deferoxamine and ferritin levels in serum (pharmacokinetics).

    Measured: 72h

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionDec 2011
  4. Study completionDec 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00777140
Sponsor's protocol ID
TANDEM-1
Other IDs
EUDRACT: 2007-006731-31
Acronym
TANDEM-1
Status last verified
Aug 2022
First submitted
21 Oct 2008
Last updated
8 Aug 2022
Results posted
No
Data monitoring committee
Yes

Publications

  • Kontos HA. Oxygen radicals in cerebral ischemia: the 2001 Willis lecture. Stroke. 2001 Nov;32(11):2712-6. doi: 10.1161/hs1101.098653.

    PubMed 11692043

  • Selim MH, Ratan RR. The role of iron neurotoxicity in ischemic stroke. Ageing Res Rev. 2004 Jul;3(3):345-53. doi: 10.1016/j.arr.2004.04.001.

    PubMed 15231241

  • Castellanos M, Puig N, Carbonell T, Castillo J, Martinez J, Rama R, Davalos A. Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats. Brain Res. 2002 Oct 11;952(1):1-6. doi: 10.1016/s0006-8993(02)03179-7.

    PubMed 12363398

  • Millan M, Sobrino T, Castellanos M, Nombela F, Arenillas JF, Riva E, Cristobo I, Garcia MM, Vivancos J, Serena J, Moro MA, Castillo J, Davalos A. Increased body iron stores are associated with poor outcome after thrombolytic treatment in acute stroke. Stroke. 2007 Jan;38(1):90-5. doi: 10.1161/01.STR.0000251798.25803.e0. Epub 2006 Nov 30.

    PubMed 17138950

  • Davalos A, Castillo J, Marrugat J, Fernandez-Real JM, Armengou A, Cacabelos P, Rama R. Body iron stores and early neurologic deterioration in acute cerebral infarction. Neurology. 2000 Apr 25;54(8):1568-74. doi: 10.1212/wnl.54.8.1568.

    PubMed 10762495

  • Davalos A, Fernandez-Real JM, Ricart W, Soler S, Molins A, Planas E, Genis D. Iron-related damage in acute ischemic stroke. Stroke. 1994 Aug;25(8):1543-6. doi: 10.1161/01.str.25.8.1543.

    PubMed 8042204

  • Erdemoglu AK, Ozbakir S. Serum ferritin levels and early prognosis of stroke. Eur J Neurol. 2002 Nov;9(6):633-7. doi: 10.1046/j.1468-1331.2002.00472.x.

    PubMed 12453079

  • Soloniuk DS, Perkins E, Wilson JR. Use of allopurinol and deferoxamine in cellular protection during ischemia. Surg Neurol. 1992 Aug;38(2):110-3. doi: 10.1016/0090-3019(92)90087-4.

    PubMed 1509342

  • Patt A, Horesh IR, Berger EM, Harken AH, Repine JE. Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. J Pediatr Surg. 1990 Feb;25(2):224-7; discussion 227-8. doi: 10.1016/0022-3468(90)90407-z.

    PubMed 2303992

  • Palmer C, Roberts RL, Bero C. Deferoxamine posttreatment reduces ischemic brain injury in neonatal rats. Stroke. 1994 May;25(5):1039-45. doi: 10.1161/01.str.25.5.1039.

    PubMed 8165675

  • Hurn PD, Koehler RC, Blizzard KK, Traystman RJ. Deferoxamine reduces early metabolic failure associated with severe cerebral ischemic acidosis in dogs. Stroke. 1995 Apr;26(4):688-94; discussion 694-5. doi: 10.1161/01.str.26.4.688.

    PubMed 7709418

  • Freret T, Valable S, Chazalviel L, Saulnier R, Mackenzie ET, Petit E, Bernaudin M, Boulouard M, Schumann-Bard P. Delayed administration of deferoxamine reduces brain damage and promotes functional recovery after transient focal cerebral ischemia in the rat. Eur J Neurosci. 2006 Apr;23(7):1757-65. doi: 10.1111/j.1460-9568.2006.04699.x.

    PubMed 16623832

  • Kim HJ, Hida H, Jung CG, Miura Y, Nishino H. Treatment with deferoxamine increases neurons from neural stem/progenitor cells. Brain Res. 2006 May 30;1092(1):1-15. doi: 10.1016/j.brainres.2006.02.046. Epub 2006 May 12.

    PubMed 16697980

  • Summers MR, Jacobs A, Tudway D, Perera P, Ricketts C. Studies in desferrioxamine and ferrioxamine metabolism in normal and iron-loaded subjects. Br J Haematol. 1979 Aug;42(4):547-55. doi: 10.1111/j.1365-2141.1979.tb01167.x.

    PubMed 476006

  • Allain P, Mauras Y, Chaleil D, Simon P, Ang KS, Cam G, Le Mignon L, Simon M. Pharmacokinetics and renal elimination of desferrioxamine and ferrioxamine in healthy subjects and patients with haemochromatosis. Br J Clin Pharmacol. 1987 Aug;24(2):207-12. doi: 10.1111/j.1365-2125.1987.tb03163.x.

    PubMed 3620295

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Deferoxamine in people with Ischemic Stroke, Acute, run by Germans Trias i Pujol Hospital at 4 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical and Analytical Adverse Events (anemia, hypotension, renal failure, mortality, hemorrhagic transformation, cerebral edema, other severe adverse events) (time frame: 3 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00777140, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022; AzTrials last refreshed its copy on 7 Nov 2026.

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