High-Dose Deferoxamine in Intracerebral Hemorrhage

NCT01662895 | Terminated Phase 2 Results DMC

• 2 other identifiers: 2012P-000005U01NS074425
• Study Type: interventional
• Target: 42
• Locations: 2 countries
• Sites: 29

Brief Summary

The main 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 brain hemorrhage.

Conditions

Intracerebral Hemorrhage

Keywords

Brain hemorrhage; Cerebral Hemorrhage; Deferoxamine; Hi-DEF Trial

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Modified Rankin Scale (mRS) Score 0-2

  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 minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).

  90 days

Secondary Outcomes (1)

• Number of Subjects With mRS Score 0-3

  90 days

Other Outcomes (5)

• Number of Subjects With Allergic/Anaphylactic Reaction

  within 7 days or discharge

• Number of Patients With Hypotension

  within 7 days or discharge

• Number of Patients With New Visual or Auditory Changes

  within 7 days or discharge

Study Arms (2)

Deferoxamine

ACTIVE COMPARATOR

Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.

Drug: Deferoxamine

Normal Saline

PLACEBO COMPARATOR

0.9% sodium chloride

Drug: Normal saline

Interventions

Deferoxamine DRUG

Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.

Also known as: Deferoxamine Mesylate

Deferoxamine

Normal saline DRUG

This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.

Also known as: 0.90% Sodium Chloride Solution

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 can 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 low-molecular-weight heparin
• 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
• 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

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
• Tufts Medical Center: collaborator
• University of Massachusetts, Worcester: collaborator
• University of Pennsylvania: collaborator
• Johns Hopkins University: collaborator
• University of Maryland: collaborator
• University of Virginia: collaborator
• Duke University: collaborator
• University of North Carolina: collaborator
• University of Florida: collaborator
• The Cleveland Clinic: 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 Hospital: 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
• Dalhousie University: collaborator

Study Sites (29)

St. Joseph's Hospital

Phoenix, Arizona, 85013, United States

Location

Stanford University Hospital

Palo Alto, California, 94304, United States

Location

San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Hartford Hospital

Hartford, Connecticut, 06107, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

The University of Florida College of Medicine

Jacksonville, Florida, 32209, United States

Location

University of Iowa Hospital

Iowa City, Iowa, 52242, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

University of North Carolina Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

Duke University Hospital

Durham, North Carolina, 27705, United States

Location

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

The Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

The University of Texas Health Science Center

Houston, Texas, 77030, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Foothills Medical Center

Calgary, Alberta, T2N 2T9, Canada

Location

Mackenzie Health Sciences Centre

Edmonton, Alberta, T6G 2B7, Canada

Location

Halifax Infirmary

Halifax, Nova Scotia, B3H 3A7, Canada

Location

Hôpital de l'Enfant-Jésus - CHU de Québec

Québec, G1J 1Z4, Canada

Location

Related Publications (6)

• 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

• 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

• Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009 Jun;40(6):2241-3. doi: 10.1161/STROKEAHA.108.539536. Epub 2009 Apr 16.

  PMID: 19372448 BACKGROUND

• Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.

  PMID: 19286595 BACKGROUND

• Roh DJ, Poyraz FC, Mao E, Shen Q, Kansara V, Cottarelli A, Song S, Nemkov T, Kumar A, Hudson KE, Ghoshal S, Park S, Agarwal S, Connolly ES, Claassen J, Kreuziger LB, Hod E, Yeatts S, Foster LD, Selim M. Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome. J Am Heart Assoc. 2024 Jul 16;13(14):e035524. doi: 10.1161/JAHA.124.035524. Epub 2024 Jul 9.

  PMID: 38979830 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Intracranial Hemorrhages

Interventions

Deferoxamine; Saline Solution; Sodium Chloride

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; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Limitations and Caveats

The study was terminated prematurely, and only 42 subjects were enrolled. As a result, any formal evaluation of these outcomes would be under-powered. Only descriptive statistics are provided.

Results Point of Contact

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

mselim@bidmc.harvard.edu

617-63208913

Study Officials

• Magdy Selim, MD, PhD

  Beth Israel Deaconess Medical Center/Harvard Medical School

  PRINCIPAL INVESTIGATOR

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: Professor of Neurology

Study Record Dates

• First Submitted: July 30, 2012
• First Posted: August 13, 2012
• Study Start: March 18, 2013
• Primary Completion: January 15, 2014
• Study Completion: May 10, 2018
• Last Updated: June 12, 2019
• Results First Posted: May 30, 2019

Record last verified: 2019-05

Locations

CA (4); US (25)