Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial

NCT02175225 | Completed Phase 2 Results DMC

• 2 other identifiers: 2012P000005U01NS074425
• Study Type: interventional
• Target: 294
• Locations: 2 countries
• Sites: 28

Brief 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 to examine its effectiveness as a treatment for intracerebral hemorrhage.

Conditions

Intracerebral Hemorrhage

Keywords

Brain hemorrhage; Cerebral hemorrhage; Bleeding in the brain; Deferoxamine; iDEF trial

Outcome Measures

Primary Outcomes (3)

• 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.

  90 days

• Number of Subjects Experiencing Serious Adverse Events

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

  90 days

• Number of Subjects With Serious Adverse Events Within 7 Days

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

  7 days

Secondary Outcomes (4)

• Proportion of Patients With mRS Score 0-3 at 90 Days

  90 days

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

  180 days

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

  180 days

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

  90 days

Other Outcomes (7)

• Ordinal Distribution of Scores on mRS at Day 90

  90 days

• Ordinal Distribution of Scores on mRS at 180 Days

  180 days

• Adverse Event of Special Interest: Number of Patients With Allergic Reactions (During Infusion of Study Drug)

  during the study infusion

Study Arms (2)

Deferoxamine Mesylate

EXPERIMENTAL

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

Drug: Deferoxamine Mesylate

Normal Saline

PLACEBO COMPARATOR

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

Drug: Placebo (for Deferoxamine Mesylate)

Interventions

Deferoxamine Mesylate DRUG

Deferoxamine Mesylate

Placebo (for Deferoxamine Mesylate) DRUG

Normal Saline

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• Medical University of South Carolina: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Massachusetts General Hospital: collaborator
• University of Massachusetts, Worcester: collaborator
• University of Pennsylvania: collaborator
• Johns Hopkins University: collaborator
• Duke University: collaborator
• University of North Carolina: collaborator
• University of Florida: collaborator
• Henry Ford Hospital: collaborator
• Ohio State University: collaborator
• St. Joseph's Hospital and Medical Center, Phoenix: collaborator
• University of California, San Francisco: collaborator
• Oregon Health and Science University: collaborator
• Yale New Haven Health System Center for Healthcare Solutions: collaborator
• University of Iowa: collaborator
• Hartford Hospital: collaborator
• The University of Texas Health Science Center, Houston: collaborator
• Rhode Island Hospital: collaborator
• Stanford University: collaborator
• University of Washington: collaborator
• University of Calgary: collaborator
• Hopital de l'Enfant-Jesus: collaborator
• University of Alberta: collaborator
• Rush University Medical Center: collaborator
• University Hospitals Cleveland Medical Center: collaborator
• Columbia University: collaborator
• Weill Medical College of Cornell University: collaborator
• NYU Langone Health: collaborator
• Mount Sinai Hospital, New York: collaborator
• Loyola University: collaborator

Study Sites (28)

St. Joseph's Hospital / Barrow Neurological Institute

Phoenix, Arizona, United States

Location

Stanford University Medical Center

Palo Alto, California, United States

Location

San Francisco General Hospital

San Francisco, California, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, United States

Location

University of Florida

Jacksonville, Florida, United States

Location

Loyola University Medical Center

Chicago, Illinois, United States

Location

RUSH University Medical Center

Chicago, Illinois, United States

Location

University of Iowa Medical Center

Iowa City, Iowa, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Location

Henry Ford Hospital

Detroit, Michigan, United States

Location

Columbia University

New York, New York, United States

Location

Mount Sinai Hospital

New York, New York, United States

Location

NYU Langone Medical Center

New York, New York, United States

Location

Weill Medical College of Cornell University

New York, New York, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, United States

Location

Duke University Medical Center

Durham, North Carolina, United States

Location

University Hospital Case Medical Center

Cleveland, Ohio, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, United States

Location

Oregon Health & Science University Medical Center

Portland, Oregon, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, United States

Location

Rhode Island Hospital

Providence, Rhode Island, United States

Location

Medical University of South Carolina

Charleston, South Carolina, United States

Location

University of Texas Health Sciences Center

Houston, Texas, United States

Location

Foothills Hospital - University of Calgary

Calgary, Alberta, Canada

Location

University of Alberta - Mackenzie Health Sciences Centre

Edmonton, Alberta, Canada

Location

CHU de Québec - Hôpital de l'Enfant-Jésus

Québec, Canada

Location

Related Publications (14)

• 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.

  PMID: 23943316 BACKGROUND

• 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.

  PMID: 21868742 BACKGROUND

• 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.

  PMID: 19064798 BACKGROUND

• 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.

  PMID: 24187595 BACKGROUND

• 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.

  PMID: 24172580 BACKGROUND

• 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.

  PMID: 20044521 BACKGROUND

• 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.

  PMID: 24366522 BACKGROUND

• 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.

  PMID: 40789806 DERIVED

• 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.

  PMID: 40399657 DERIVED

• 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.

  PMID: 35676589 DERIVED

• 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.

  PMID: 35306827 DERIVED

• 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.

  PMID: 34789008 DERIVED

• 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.

  PMID: 33758069 DERIVED

• 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.

  PMID: 30898550 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Intracranial Hemorrhages

Interventions

Deferoxamine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Magdy Selim, MD, PhD
• Organization: Beth Israel Deaconess Medical Center

mselim@bidmc.harvard.edu

617-632-8913

Study Officials

• Magdy Selim, MD, PhD

  Beth Israel Deaconess Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: June 26, 2014
• Study Start: October 1, 2014
• Primary Completion: February 10, 2018
• Study Completion: May 30, 2018
• Last Updated: May 30, 2019
• Results First Posted: May 30, 2019

Record last verified: 2019-05

Locations

US (25); CA (3)