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

NCT00598572 | Completed Phase 1 DMC

• 2 other identifiers: 2007P0002881R01NS057127-01A1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Intracerebral Hemorrhage

Keywords

Deferoxamine; Safety; Intracerebral hemorrhage

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicities

  First 7 days of hospitalization or diacharge, whichever occurs earlier

Study Arms (1)

1

EXPERIMENTAL

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

Interventions

Deferoxamine Mesylate 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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Massachusetts General Hospital: collaborator
• Medical College of Wisconsin: collaborator
• Medical University of South Carolina: collaborator
• Hartford Hospital: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Deferoxamine

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hydroxamic Acids; Hydroxylamines; Amines; Organic Chemicals; Hydroxy Acids; Carboxylic Acids

Study Officials

• Magdy Selim, MD, PhD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: January 10, 2008
• First Posted: January 22, 2008
• Study Start: July 1, 2008
• Primary Completion: January 1, 2010
• Study Completion: April 1, 2010
• Last Updated: January 16, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)