Dose Finding and Safety Study of Deferoxamine in Patients With Brain Hemorrhage (DFO In ICH)

This study has been completed.
Sponsor:
Collaborators:
Massachusetts General Hospital
Medical College of Wisconsin
Medical University of South Carolina
Hartford Hospital
Information provided by:
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00598572
First received: January 10, 2008
Last updated: February 16, 2011
Last verified: February 2011
  Purpose

Animal studies show that the breakdown of blood results in iron accumulation in the brain after brain hemorrhage (ICH); and that iron plays a role in brain injury in ICH patients. Deferoxamine (DFO) has been extensively used in clinical practice for more than 30 years to remove excessive iron from the body, and has been shown to provide some benefit in animal studies of ICH. Therefore, we plan to undertake this study to evaluate the safety and tolerability of treatment with DFO in patients with ICH, and to determine the maximal tolerated dose to be used in future studies to determine if treatment with DFO can improve the outcome of patients with ICH.

Our main objectives are: 1) to evaluate the safety and tolerability of varying doses of DFO, by determining the treatment related adverse events, in patients with ICH; and 2) to determine the maximal tolerated dose to be adopted in subsequent studies to test the efficacy of DFO in improving outcome after ICH.

We hypothesize that DFO is well-tolerated and has minimal serious adverse effects in patients with ICH; and that treatment with DFO will improve patients' outcome. The results can potentially bring into account new means to improve the outcome of patients with ICH. ICH is a frequent cause of disability and death. A successful study demonstrating the efficacy of iron-modifying therapy would be of considerable public health significance.


Condition Intervention Phase
Intracerebral Hemorrhage
Drug: Deferoxamine Mesylate
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Dose-limiting toxicities [ Time Frame: First 7 days of hospitalization or diacharge, whichever occurs earlier ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: July 2008
Study Completion Date: April 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All participants will receive various dose-regimens of the study drug. Each dose cohort will consist of at least 3 subjects.
Drug: Deferoxamine Mesylate
Various dose-regimens ranging from 7 mg/kg to 125 mg/kg (with a maximum allowable total daily dose of 6000 mg at any of the tested dose tiers, regardless of patient's weight), administered daily by IV infusion for three consecutive days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years
  2. The diagnosis of ICH is confirmed by brain CT scan.
  3. The first dose of the study drug can be administered within 18 hours of ICH symptom onset.
  4. Signed and dated informed consent is obtained
  5. Stable clinical and neurological status. Patients whose clinical or neurological status significantly deteriorates compared to presentation prior to administration of the study drug will be excluded.

Exclusion Criteria:

  1. Previous chelation therapy or known hypersensitivity to DFO products
  2. Abnormal renal function (serum creatinine > 2 mg/dl)
  3. Known severe iron deficiency anemia
  4. Planned surgical evacuation of ICH prior to administration of the study drug
  5. Patients with suspected secondary ICH related to tumour, coagulopathy, ruptured aneurysm or arteriovenous malformation, or venous sinus thrombosis
  6. Evidence of significant shift of midline brain structure (> 10 mm) or herniation on imaging studies.
  7. Deep coma (Glasgow Coma Score (GCS) = 3-5) upon presentation
  8. Taking iron supplements or prochlorperazine
  9. Patients with heart failure taking > 500 mg of vitamin C daily
  10. Known hearing impairment
  11. Systolic blood pressure < 100 mmHg or diastolic blood pressure < 60 mmHg, confirmed by 3 consecutive readings
  12. Significant chronic respiratory insufficiency
  13. Known pregnancy (or positive pregnancy test), or breast-feeding
  14. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, incompliance, or any other cause.
  15. Any condition which, in the judgement of the investigator, might increase the risk to the patient
  16. Life expectancy of less than 90 days due to co-morbid conditions
  17. Concurrent participation in another research protocol for investigation of another experimental therapy
  18. Pre-existing Do Not Resuscitate (DNR) order, or indication that a new DNR order will be implemented within the first 48 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: NCT00598572

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Medical College of Wisconsin
Medical University of South Carolina
Hartford Hospital
Investigators
Principal Investigator: Magdy Selim, MD, PhD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Magdy Selim, MD, PhD - Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00598572     History of Changes
Other Study ID Numbers: 2007-P-000288/1, 1R01NS057127 - 01A1
Study First Received: January 10, 2008
Last Updated: February 16, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Beth Israel Deaconess Medical Center:
Deferoxamine
Safety
Intracerebral hemorrhage

Additional relevant MeSH terms:
Hemorrhage
Intracranial Hemorrhages
Cerebral Hemorrhage
Pathologic Processes
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 July 31, 2014