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Intracerebral HemorrhagePhase 2NCT02175225

Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial

A Phase 2 study testing Deferoxamine Mesylate in people with Intracerebral Hemorrhage, run by Beth Israel Deaconess Medical Center at 28 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

The investigators hypothesize that treatment with the iron chelator, Deferoxamine Mesylate, improves the outcome of patients with brain hemorrhage. The purpose of this study is to determine whether treatment with Deferoxamine Mesylate is of sufficient promise to improve outcome before pursuing a larger clinical trial… Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Intracerebral Hemorrhage
What is being tested?
Deferoxamine Mesylate
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
294 participants
Where
28 sitesin 2 countries
Study dates
Oct 2014to 30 May 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 and ≤ 80 years
  • The diagnosis of ICH is confirmed by brain CT scan
  • NIHSS score ≥6 and GCS >6 upon presentation
  • The first dose of the study drug is expected to be administered within 24h of ICH symptom onset
  • Functional independence prior to ICH, defined as pre-ICH mRS ≤1
  • Signed and dated informed consent is obtained.

Who cannot join

  • Previous chelation therapy or known hypersensitivity to DFO products
  • Known severe iron deficiency anemia (defined as hemoglobin concentration < 7g/dL or requiring blood transfusions)
  • Abnormal renal function, defined as serum creatinine >2 mg/dL
  • Planned surgical evacuation of ICH prior to administration of study drug (placement of a catheter for ventricular drainage is not a contraindication to enrollment)
  • SUSPECTED secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
  • Infratentorial hemorrhage
Show all 31Show fewer
  • Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)
  • Complete unconsciousness, defined as a score of 3 on item 1a of the NIHSS (Responds only with reflex motor or autonomic effects or totally unresponsive, and flaccid)
  • Pre-existing disability, defined as pre-ICH mRS ≥2
  • Coagulopathy - defined as elevated aPTT or INR >1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban or apixaban), or low-molecular-weight heparin
  • Patients with confirmed aspiration, pneumonia, or evident bilateral pulmonary infiltrates on chest x-ray or CT scan prior to enrollment
  • Patients with significant respiratory disease such as chronic obstructive pulmonary disease, pulmonary fibrosis, or any use (chronic or intermittent) of inhaled O2 at home
  • FiO2 >0.35 (>4 L/min) prior to enrollment
  • Sepsis (present source of infection ± lactic acidosis); Systemic Inflammatory Response Syndrome (Temp >100.4F or <96.8F; Heart rate >90; Respiratory rate >20 or PaCo2 <32 mmHg; WBC >12, <4, or bands >10%); or shock (SBP <90 mmHg) at presentation
  • The presence of 4 or more of the following risk modifiers for ARDS prior to enrollment:
  • Tachypnea (respiratory rate >30)
  • SpO2 <95%
  • Obesity (BMI >30)
  • Acidosis (pH <7.35)
  • Hypoalbuminemia (albumin <3.5 g/dL)
  • Concurrent use of chemotherapy
  • Taking iron supplements containing ≥ 325 mg of ferrous iron, or prochlorperazine
  • Patients with heart failure taking > 500 mg of vitamin C daily
  • Known severe hearing loss
  • Known pregnancy, or positive pregnancy test, or breastfeeding
  • Positive drug screen for cocaine upon presentation
  • Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, noncompliance, living in another state or any other cause
  • Any condition which, in the judgement of the investigator, might increase the risk to the patient
  • Life expectancy of less than 90 days due to co-morbid conditions
  • Concurrent participation in another research protocol for investigation of another experimental therapy
  • Indication that a new DNR or Comfort Measures Only (CMO) order will be implemented within the first 72 hours of hospitalization

Trial locations and contacts

28 sites in 2 countries.

28 sites in 2 countries

United States25 sites
  • Johns Hopkins Hospital

    Baltimore, Maryland

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts

  • University of North Carolina Medical Center

    Chapel Hill, North Carolina

  • Medical University of South Carolina

    Charleston, South Carolina

  • Loyola University Medical Center

    Chicago, Illinois

  • RUSH University Medical Center

    Chicago, Illinois

  • University Hospital Case Medical Center

    Cleveland, Ohio

  • The Ohio State University Medical Center

    Columbus, Ohio

  • Henry Ford Hospital

    Detroit, Michigan

  • Duke University Medical Center

    Durham, North Carolina

  • University of Texas Health Sciences Center

    Houston, Texas

  • University of Iowa Medical Center

    Iowa City, Iowa

  • University of Florida

    Jacksonville, Florida

  • Yale New Haven Hospital

    New Haven, Connecticut

  • Columbia University

    New York, New York

  • Mount Sinai Hospital

    New York, New York

  • NYU Langone Medical Center

    New York, New York

  • Weill Medical College of Cornell University

    New York, New York

  • Stanford University Medical Center

    Palo Alto, California

  • University of Pennsylvania Medical Center

    Philadelphia, Pennsylvania

  • St. Joseph's Hospital / Barrow Neurological Institute

    Phoenix, Arizona

  • Oregon Health & Science University Medical Center

    Portland, Oregon

  • Rhode Island Hospital

    Providence, Rhode Island

  • San Francisco General Hospital

    San Francisco, California

  • UMass Memorial Medical Center

    Worcester, Massachusetts

Other trials in United States

Canada3 sites
  • Foothills Hospital - University of Calgary

    Calgary, Alberta

  • University of Alberta - Mackenzie Health Sciences Centre

    Edmonton, Alberta

  • CHU de Québec - Hôpital de l'Enfant-Jésus

    Québec

Other trials in Canada

About this study

Official title: Study of Deferoxamine Mesylate in Intracerebral Hemorrhage

The investigators hypothesize that treatment with the iron chelator, Deferoxamine Mesylate, improves the outcome of patients with brain hemorrhage.

The purpose of this study is to determine whether treatment with Deferoxamine Mesylate is of sufficient promise to improve outcome before pursuing a larger clinical trial to examine its effectiveness as a treatment for intracerebral hemorrhage.

Read the detailed description

This is a prospective, multi-center, double-blind, randomized, placebo-controlled, phase-II clinical trial.

Subjects will be randomized to either deferoxamine mesylate (DFO) at 32 mg/kg/day (up to a maximum daily dose of 6000 mg/day), or saline placebo, given by IV infusion for 3 consecutive days.

Treatment will be initiated within 24 hours after ICH symptom onset. Randomization will control baseline imbalances associated with baseline ICH score, ICH onset-to-treatment time (OTT), ICH volume, baseline NIHSS score, and warfarin use.

All subjects will be followed for 6 months and will receive standard of care therapy while participating in the study.

Throughout the study, we will continue to assess the safety of DFO. At the conclusion of the study, the proportion of DFO-treated subjects with a good clinical outcome at 3 months (defined as modified Rankin Scale (mRS) score of 0-2) will be compared to the placebo proportion in a futility analysis to determine if it is futile to move DFO forward to Phase III efficacy evaluation.

Being tested
Deferoxamine Mesylate, Placebo (for Deferoxamine Mesylate)
Keywords
Brain hemorrhage, Cerebral hemorrhage, Bleeding in the brain, Deferoxamine, iDEF trial
Medical subject headings
Cerebral Hemorrhage, Intracranial Hemorrhages

What participants receive

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

  • Deferoxamine MesylateDrug

  • Placebo (for Deferoxamine Mesylate)Drug

Study groups in NCT02175225
Study groupRoleWhat they receive
Deferoxamine MesylateExperimentalDeferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days
Receives: Drug: Deferoxamine Mesylate
Normal SalinePlacebo comparatorNormal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days
Receives: Drug: Placebo (for Deferoxamine Mesylate)

What is being measured

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

  1. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days

    The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

    Measured: 90 days

  2. Number of Subjects Experiencing Serious Adverse Events

    Number of subjects experiencing Serious adverse events at any time from randomization through day 90

    Measured: 90 days

  3. Number of Subjects With Serious Adverse Events Within 7 Days

    Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization

    Measured: 7 days

Secondary outcomes (4)
  1. Proportion of Patients With mRS Score 0-3 at 90 Days

    Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 90 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

    Although mRS 0-3 is less favorable than the primary outcome of mRS 0-2, it would still be a desirable effect in patients with ICH given that no treatments exist to reduce disability.

    Measured: 90 days

  2. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 180 Days

    Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

    Measured: 180 days

  3. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-3 at 180 Days

    Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

    Measured: 180 days

  4. Proportion of Subjects With Good Outcome (mRS 0-2) in the Early vs. Delayed Treatment Time Windows

    Analyses will be expanded to include an interaction between treatment and OTT window and the magnitude of the treatment effect, and corresponding confidence interval, will be estimated for each time window (<12 hours vs. >/= 12 hours) in order to explore the presence of a differential treatment effect in the OTT windows.

    Measured: 90 days

Timeline

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

  1. First posted26 Jun 2014 (estimated)
  2. Study startOct 2014
  3. Primary completion10 Feb 2018
  4. Study completion30 May 2018

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
294 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02175225
Sponsor's protocol ID
2012P000005
Other IDs
U01NS074425
Status last verified
May 2019
First submitted
25 Jun 2014
Last updated
30 May 2019
Data monitoring committee
Yes

Publications

  • Yeatts SD, Palesch YY, Moy CS, Selim M. High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013 Oct;19(2):257-66. doi: 10.1007/s12028-013-9861-y.

    PubMed 23943316
  • Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, Palesch Y; Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011 Nov;42(11):3067-74. doi: 10.1161/STROKEAHA.111.617589. Epub 2011 Aug 25.

    PubMed 21868742
  • Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009 Mar;40(3 Suppl):S90-1. doi: 10.1161/STROKEAHA.108.533125. Epub 2008 Dec 8.

    PubMed 19064798
  • Hatakeyama T, Okauchi M, Hua Y, Keep RF, Xi G. Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats. Transl Stroke Res. 2013 Oct;4(5):546-53. doi: 10.1007/s12975-013-0270-5.

    PubMed 24187595
  • Xie Q, Gu Y, Hua Y, Liu W, Keep RF, Xi G. Deferoxamine attenuates white matter injury in a piglet intracerebral hemorrhage model. Stroke. 2014 Jan;45(1):290-2. doi: 10.1161/STROKEAHA.113.003033. Epub 2013 Oct 30.

    PubMed 24172580
  • Okauchi M, Hua Y, Keep RF, Morgenstern LB, Schallert T, Xi G. Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration. Stroke. 2010 Feb;41(2):375-82. doi: 10.1161/STROKEAHA.109.569830. Epub 2009 Dec 31.

    PubMed 20044521
  • Sonni S, Lioutas VA, Selim MH. New avenues for treatment of intracranial hemorrhage. Curr Treat Options Cardiovasc Med. 2014 Jan;16(1):277. doi: 10.1007/s11936-013-0277-y.

    PubMed 24366522
  • Polymeris AA, Lioutas VA, Incontri D, Soman S, Selim MH; i-DEF Investigators. Evolution of Perihematomal Edema Mean Hounsfield Unit and Its Association with Clinical Outcome in Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial. Neurocrit Care. 2025 Dec;43(3):824-833. doi: 10.1007/s12028-025-02337-7. Epub 2025 Aug 11.

    PubMed 40789806
  • Polymeris AA, Lioutas VA, Foster LD, Incontri D, Heistand EC, Marchal J, Lazar A, Fischer U, Engelter ST, Seiffge DJ, Yeatts SD, Selim MH. Early neurological improvement with deferoxamine after intracerebral hemorrhage: A post hoc analysis of the i-DEF trial. Int J Stroke. 2025 Dec;20(10):1235-1245. doi: 10.1177/17474930251348088. Epub 2025 May 26.

    PubMed 40418029
  • Polymeris AA, Lioutas VA, Marchina S, Seiffge DJ, Roh DJ, Poyraz FC, Selim MH; i-DEF Investigators. Hemoglobin and Perihematomal Edema After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial. Neurocrit Care. 2026 Feb;44(1):64-71. doi: 10.1007/s12028-025-02284-3. Epub 2025 May 21.

    PubMed 40399657
  • Lee KH, Lioutas VA, Marchina S, Selim M; iDEF Investigators. The Prognostic Roles of Perihematomal Edema and Ventricular Size in Patients with Intracerebral Hemorrhage. Neurocrit Care. 2022 Oct;37(2):455-462. doi: 10.1007/s12028-022-01532-0. Epub 2022 Jun 8.

    PubMed 35676589
  • Foster L, Robinson L, Yeatts SD, Conwit RA, Shehadah A, Lioutas V, Selim M; i-DEF Investigators. Effect of Deferoxamine on Trajectory of Recovery After Intracerebral Hemorrhage: A Post Hoc Analysis of the i-DEF Trial. Stroke. 2022 Jul;53(7):2204-2210. doi: 10.1161/STROKEAHA.121.037298. Epub 2022 Mar 21.

    PubMed 35306827
  • Wei C, Wang J, Foster LD, Yeatts SD, Moy C, Mocco J, Selim M; i-DEF Investigators. Effect of Deferoxamine on Outcome According to Baseline Hematoma Volume: A Post Hoc Analysis of the i-DEF Trial. Stroke. 2022 Apr;53(4):1149-1156. doi: 10.1161/STROKEAHA.121.035421. Epub 2021 Nov 18.

    PubMed 34789008
  • Lun R, Yogendrakumar V, Ramsay T, Shamy M, Fahed R, Selim MH, Dowlatshahi D. Predicting long-term outcomes in acute intracerebral haemorrhage using delayed prognostication scores. Stroke Vasc Neurol. 2021 Dec;6(4):536-541. doi: 10.1136/svn-2020-000656. Epub 2021 Mar 23.

    PubMed 33758069
  • Selim M, Foster LD, Moy CS, Xi G, Hill MD, Morgenstern LB, Greenberg SM, James ML, Singh V, Clark WM, Norton C, Palesch YY, Yeatts SD; i-DEF Investigators. Deferoxamine mesylate in patients with intracerebral haemorrhage (i-DEF): a multicentre, randomised, placebo-controlled, double-blind phase 2 trial. Lancet Neurol. 2019 May;18(5):428-438. doi: 10.1016/S1474-4422(19)30069-9. Epub 2019 Mar 18.

    PubMed 30898550

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Deferoxamine Mesylate in people with Intracerebral Hemorrhage, run by Beth Israel Deaconess Medical Center at 28 sites in 2 countries.

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 6 inclusion and 31 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 30 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Canada. 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?

Yes. Results are posted in the registry (first posted 30 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days (time frame: 90 days). The study lists 3 primary outcomes in all. 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 NCT02175225, which also lists 15 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 30 May 2019.

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