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

Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

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.

Study Overview

• Status: Completed
• Conditions: Intracerebral Hemorrhage
• Intervention / Treatment: Drug: Deferoxamine Mesylate

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicities	First 7 days of hospitalization or diacharge, whichever occurs earlier

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Medical University of South Carolina; Massachusetts General Hospital; National Institute of Neurological Disorders and Stroke (NINDS); Medical College of Wisconsin; Hartford Hospital
• Investigators: Principal Investigator: Magdy Selim, MD, PhD, Beth Israel Deaconess Medical Center

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: January 10, 2008
• First Submitted That Met QC Criteria: January 21, 2008
• First Posted (Estimate): January 22, 2008

Study Record Updates

• Last Update Posted (Actual): January 16, 2018
• Last Update Submitted That Met QC Criteria: January 11, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Safety; Deferoxamine; Intracerebral hemorrhage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Siderophores; Deferoxamine
• Other Study ID Numbers: 2007P000288; 1R01NS057127-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO