Dose Finding and Safety Study of Deferoxamine in Patients With Brain Hemorrhage - Full Text View

Sponsors and Collaborators:	Beth Israel Deaconess Medical Center National Institute of Neurological Disorders and Stroke (NINDS) Massachusetts General Hospital Medical College of Wisconsin Medical University of South Carolina
Information provided by:	Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT00598572

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 I

Drug Information available for: Deferoxamine Deferoxamine mesylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Open Label, Active Control, Single Group Assignment, Safety Study
Official Title:	Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

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 ]

Estimated Enrollment:	24
Study Start Date:	July 2008
Estimated Study Completion Date:	June 2011
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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:

Age ≥ 18 years
The diagnosis of ICH is confirmed by brain CT scan.
The first dose of the study drug can be administered within 18 hours of ICH symptom onset.
Signed and dated informed consent is obtained
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:

Previous chelation therapy or known hypersensitivity to DFO products
Abnormal renal function (serum creatinine > 2 mg/dl)
Known severe iron deficiency anemia
Planned surgical evacuation of ICH prior to administration of the study drug
Patients with suspected secondary ICH related to tumour, coagulopathy, ruptured aneurysm or arteriovenous malformation, or venous sinus thrombosis
Evidence of significant shift of midline brain structure (> 10 mm) or herniation on imaging studies.
Deep coma (Glasgow Coma Score (GCS) = 3-5) upon presentation
Taking iron supplements or prochlorperazine
Patients with heart failure taking > 500 mg of vitamin C daily
Known hearing impairment
Systolic blood pressure < 100 mmHg or diastolic blood pressure < 60 mmHg, confirmed by 3 consecutive readings
Significant chronic respiratory insufficiency
Known pregnancy (or positive pregnancy test), or breast-feeding
Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, incompliance, 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
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

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

National Institute of Neurological Disorders and Stroke (NINDS)

Massachusetts General Hospital

Medical College of Wisconsin

Medical University of South Carolina

Investigators

Principal Investigator:

Magdy Selim, MD, PhD

Beth Israel Deaconess Medical Center

More Information

Responsible Party:	Beth Israel Deaconess Medical Center ( Magdy Selim, MD, PhD - Principal Investigator )
Study ID Numbers:	2007-P-000288/1, 1R01NS057127 - 01A1
Study First Received:	January 10, 2008
Last Updated:	August 15, 2008
ClinicalTrials.gov Identifier:	NCT00598572
Health Authority:	United States: Food and Drug Administration

Keywords provided by Beth Israel Deaconess Medical Center:

Deferoxamine
Safety
Intracerebral hemorrhage

Study placed in the following topic categories:

Signs and Symptoms
Cerebral Hemorrhage
Vascular Diseases
Central Nervous System Diseases
Intracranial Hemorrhages

Brain Diseases
Hemorrhage
Iron
Cerebrovascular Disorders
Deferoxamine

Additional relevant MeSH terms:

Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Iron Chelating Agents

Cardiovascular Diseases
Chelating Agents
Pharmacologic Actions
Siderophores

ClinicalTrials.gov processed this record on January 14, 2009