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

Intracerebral Hemorrhage Clinical Trial

— DFO In ICH  

Official title:

Safety and Tolerability of Deferoxamine in Acute Cerebral Hemorrhage

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00598572
• Other study ID #: 2007P000288
• Secondary ID: 1R01NS057127-01A
• Status: Completed
• Phase: Phase 1
• First received: January 10, 2008
• Last updated: January 11, 2018
• Start date: July 2008
• Est. completion date: April 2010

Study information

• Verified date: January 2018
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. -

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

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.

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (6)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center	Hartford Hospital, Massachusetts General Hospital, Medical College of Wisconsin, Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities		First 7 days of hospitalization or diacharge, whichever occurs earlier