Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial

NCT ID: NCT02175225

Last Updated: 2019-05-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

294 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-10-31

Study Completion Date

2018-05-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Intracerebral Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Deferoxamine Mesylate

Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days

Group Type EXPERIMENTAL

Deferoxamine Mesylate

Intervention Type DRUG

Normal Saline

Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days

Group Type PLACEBO_COMPARATOR

Placebo (for Deferoxamine Mesylate)

Intervention Type DRUG

Interventions

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Deferoxamine Mesylate

Intervention Type DRUG

Placebo (for Deferoxamine Mesylate)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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
* 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:

1. Tachypnea (respiratory rate \>30)
2. SpO2 \<95%
3. Obesity (BMI \>30)
4. Acidosis (pH \<7.35)
5. Hypoalbuminemia (albumin \<3.5 g/dL)
6. 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of South Carolina

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Massachusetts General Hospital

OTHER

Sponsor Role collaborator

University of Massachusetts, Worcester

OTHER

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role collaborator

University of North Carolina

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role collaborator

Henry Ford Hospital

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role collaborator

St. Joseph's Hospital and Medical Center, Phoenix

OTHER

Sponsor Role collaborator

University of California, San Francisco

OTHER

Sponsor Role collaborator

Oregon Health and Science University

OTHER

Sponsor Role collaborator

Yale New Haven Health System Center for Healthcare Solutions

OTHER

Sponsor Role collaborator

University of Iowa

OTHER

Sponsor Role collaborator

Hartford Hospital

OTHER

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role collaborator

Rhode Island Hospital

OTHER

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

University of Calgary

OTHER

Sponsor Role collaborator

Hopital de l'Enfant-Jesus

OTHER

Sponsor Role collaborator

University of Alberta

OTHER

Sponsor Role collaborator

Rush University Medical Center

OTHER

Sponsor Role collaborator

University Hospitals Cleveland Medical Center

OTHER

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role collaborator

NYU Langone Health

OTHER

Sponsor Role collaborator

Mount Sinai Hospital, New York

OTHER

Sponsor Role collaborator

Loyola University

OTHER

Sponsor Role collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Magdy Selim

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Magdy Selim, MD, PhD

Role: STUDY_CHAIR

Beth Israel Deaconess Medical Center

Locations

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St. Joseph's Hospital / Barrow Neurological Institute

Phoenix, Arizona, United States

Site Status

Stanford University Medical Center

Palo Alto, California, United States

Site Status

San Francisco General Hospital

San Francisco, California, United States

Site Status

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status

University of Florida

Jacksonville, Florida, United States

Site Status

Loyola University Medical Center

Chicago, Illinois, United States

Site Status

RUSH University Medical Center

Chicago, Illinois, United States

Site Status

University of Iowa Medical Center

Iowa City, Iowa, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Mount Sinai Hospital

New York, New York, United States

Site Status

NYU Langone Medical Center

New York, New York, United States

Site Status

Weill Medical College of Cornell University

New York, New York, United States

Site Status

University of North Carolina Medical Center

Chapel Hill, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

University Hospital Case Medical Center

Cleveland, Ohio, United States

Site Status

The Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

Oregon Health & Science University Medical Center

Portland, Oregon, United States

Site Status

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

University of Texas Health Sciences Center

Houston, Texas, United States

Site Status

Foothills Hospital - University of Calgary

Calgary, Alberta, Canada

Site Status

University of Alberta - Mackenzie Health Sciences Centre

Edmonton, Alberta, Canada

Site Status

CHU de Québec - Hôpital de l'Enfant-Jésus

Québec, , Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type BACKGROUND
PMID: 23943316 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21868742 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19064798 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24187595 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24172580 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20044521 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24366522 (View on PubMed)

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 Aug 11. doi: 10.1007/s12028-025-02337-7. Online ahead of print.

Reference Type DERIVED
PMID: 40789806 (View on PubMed)

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. 2025 May 21. doi: 10.1007/s12028-025-02284-3. Online ahead of print.

Reference Type DERIVED
PMID: 40399657 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35676589 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35306827 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34789008 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33758069 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30898550 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U01NS074425

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2012P000005

Identifier Type: -

Identifier Source: org_study_id

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