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

Sponsor

Beth Israel Deaconess Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00598572

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Massachusetts General Hospital (Other), Medical College of Wisconsin (Other), Medical University of South Carolina (Other), Hartford Hospital (Other)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage	Drug: Deferoxamine Mesylate	Phase 1

Detailed Description

An open-label, safety, tolerability, and dose-finding study using the continuous reassessment method.

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 All participants will receive various dose-regimens of the study drug (deferoxamine mesylate). 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.

Arm

Intervention/Treatment

Experimental: 1

All participants will receive various dose-regimens of the study drug (deferoxamine mesylate). 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.

Outcome Measures

Primary Outcome Measures

Dose-limiting toxicities [First 7 days of hospitalization or diacharge, whichever occurs earlier]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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. -