High-Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF)

This study has suspended participant recruitment.
(Recruitment halted by DSMB due to increased incidence of ARDS). Modifications to minimize dug toxicity with this high dose and the risk of ARDS are underway)
Sponsor:
Collaborators:
Medical University of South Carolina
Massachusetts General Hospital
Tufts Medical Center
University of Massachusetts, Worcester
University of Pennsylvania
Johns Hopkins University
University of Maryland
University of Virginia
Duke University
University of North Carolina
University of Florida
The Cleveland Clinic
Henry Ford Hospital
Ohio State University
St. Joseph's Hospital and Medical Center, Phoenix
University of California, San Francisco
Oregon Health and Science University
Yale New Haven Health System Center for Healthcare Solutions
University of Iowa
Hartford Hospital
The University of Texas Health Science Center, Houston
Rhode Island Hospital
Stanford University
University of Washington
University of Calgary, Foothills Hospital
CHU de Québec - Hôpital de l'Enfant-Jésus
University of Alberta
Dalhousie University
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01662895
First received: July 30, 2012
Last updated: February 25, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: Deferoxamine
Drug: Normal saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Futility Study of Deferoxamine in Intracerebral Hemorrhage

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional out-come as mRS 0-2 at 90 days.


Secondary Outcome Measures:
  • Proportion of patients with mRS score 0-3 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 3 months.

  • Proportion of patients with mRS score 0-2 in early vs. late ICH onset-to-treatment time windows [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The proportion of DFO- and placebo-treated subjects with mRS 0-2 (and 0-3) in the early (≤12h) vs. late (>12-24h) ICH onset to treatment time windows.

  • Frequency of Treatment-related Adverse Events [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    The safety endpoints will include all DFO-related adverse events until day-7 or discharge (whichever is earlier), and DFO-related SAEs and mortality through day-90.


Estimated Enrollment: 324
Study Start Date: March 2013
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Deferoxamine
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
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.
Other Name: Deferoxamine Mesylate
Placebo Comparator: Normal Saline
0.9% sodium chloride
Drug: Normal saline
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.
Other Name: 0.90% Sodium Chloride Solution

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 and ≤ 80 years
  2. The diagnosis of ICH is confirmed by brain CT scan
  3. NIHSS score ≥ 6 and GCS > 6 upon presentation
  4. The first dose of the study drug can be administered within 24h of ICH symptom onset
  5. Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1
  6. Signed and dated informed consent is obtained.

Exclusion Criteria:

  1. Previous chelation therapy or known hypersensitivity to DFO products
  2. Known severe iron deficiency anemia (defined as hemoglobin concentration < 7g/dL or requiring blood transfusions)
  3. Abnormal renal function, defined as serum creatinine > 2 mg/dL
  4. Planned surgical evacuation of ICH prior to administration of study drug (placement of a catheter for ventricular drainage is not a contraindication to enrollment)
  5. Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis
  6. Infratentorial hemorrhage
  7. Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)
  8. 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)
  9. Pre-existing disability, defined as pre-ICH mRS ≥ 2
  10. 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
  11. Taking iron supplements containing ≥ 325 mg of ferrous iron, or prochlorperazine
  12. Patients with heart failure taking > 500 mg of vitamin C daily
  13. Known severe hearing loss
  14. Known pregnancy, or positive pregnancy test, or breastfeeding
  15. 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
  16. Positive drug screen for cocaine upon presentation
  17. Any condition which, in the judgement of the investigator, might increase the risk to the patient
  18. Life expectancy of less than 90 days due to comorbid conditions
  19. Concurrent participation in another research protocol for investigation of another experimental therapy
  20. Indication that a new DNR or Comfort Measures Only (CMO) order will be implemented within the first 72 hours of hospitalization.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01662895

  Show 29 Study Locations
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Medical University of South Carolina
Massachusetts General Hospital
Tufts Medical Center
University of Massachusetts, Worcester
University of Pennsylvania
Johns Hopkins University
University of Maryland
University of Virginia
Duke University
University of North Carolina
University of Florida
The Cleveland Clinic
Henry Ford Hospital
Ohio State University
St. Joseph's Hospital and Medical Center, Phoenix
University of California, San Francisco
Oregon Health and Science University
Yale New Haven Health System Center for Healthcare Solutions
University of Iowa
Hartford Hospital
The University of Texas Health Science Center, Houston
Rhode Island Hospital
Stanford University
University of Washington
University of Calgary, Foothills Hospital
CHU de Québec - Hôpital de l'Enfant-Jésus
University of Alberta
Dalhousie University
Investigators
Principal Investigator: Magdy Selim, MD, PhD Beth Israel Deaconess Medical Center/Harvard Medical School
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01662895     History of Changes
Other Study ID Numbers: 2012P-000005, UO1NS074425
Study First Received: July 30, 2012
Last Updated: February 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Beth Israel Deaconess Medical Center:
Brain hemorrhage
Cerebral Hemorrhage
Deferoxamine
Hi-DEF Trial

Additional relevant MeSH terms:
Hemorrhage
Cerebral Hemorrhage
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Deferoxamine
Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014