Dose Finding and Safety Study of Deferoxamine in Patients With Brain Hemorrhage

NCT ID: NCT00598572

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2010-04-30

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.

Detailed Description

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

Conditions

Intracerebral Hemorrhage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

1

All participants will receive various dose-regimens of the study drug (deferoxamine mesylate). Each dose cohort will consist of at least 3 subjects.

Group Type: EXPERIMENTAL

Deferoxamine Mesylate

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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. -

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Medical College of Wisconsin

OTHER

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Hartford Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Magdy Selim

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Magdy Selim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

1R01NS057127-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2007P000288

Identifier Type: -

Identifier Source: org_study_id