HI-DEF: High-Dose Deferoxamine in Intracerebral Hemorrhage

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01662895
• Collaborator: Medical University of South Carolina (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Massachusetts General Hospital (Other), Tufts Medical Center (Other), University of Massachusetts, Worcester (Other), University of Pennsylvania (Other), Johns Hopkins University (Other), University of Maryland (Other), University of Virginia (Other), Duke University (Other), University of North Carolina (Other), University of Florida (Other), The Cleveland Clinic (Other), Henry Ford Hospital (Other), Ohio State University (Other), St. Joseph's Hospital and Medical Center, Phoenix (Other), University of California, San Francisco (Other), Oregon Health and Science University (Other), Yale New Haven Hospital (Other), University of Iowa (Other), Hartford Hospital (Other), The University of Texas Health Science Center, Houston (Other), Rhode Island Hospital (Other), Stanford University (Other), University of Washington (Other), University of Calgary (Other), Hopital de l'Enfant-Jesus (Other), University of Alberta (Other), Dalhousie University (Other)
• Enrollment: 42
• Locations: 29
• Arms: 2
• Actual Duration (Months): 61.7
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The main purpose of this study is to determine whether treatment with deferoxamine mesylate is of sufficient promise to improve outcome before pursuing a larger clinical trial to examine its effectiveness as a treatment for brain hemorrhage.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage	Drug: Deferoxamine; Drug: Normal saline	Phase 2

Detailed Description

Several studies show that hemoglobin breakdown and subsequent iron accumulation in the brain play a role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH); and that treatment with the iron chelator, deferoxamine (DFO), provides neuroprotection in animal models of ICH. The investigators recently concluded a phase-I, safety and dose-finding study of DFO in patients with ICH; repeated daily intravenous (IV) infusions of DFO in doses up to 62 mg/kg/day (up to a maximum daily dose of 6000 mg/day) were well-tolerated and did not increase serious adverse events or mortality. The current study builds on these results to assess the potential utility of DFO as a therapeutic intervention in ICH.

This is a prospective, multi-center, double-blind, randomized, placebo-armed, phase-II, futility clinical study to determine if this maximum tolerated dose of DFO is of sufficient promise to improve outcome prior to embarking on a large-scale and costly phase III study to assess its efficacy in ICH. The investigators will randomize 324 subjects with ICH equally (1:1) to either DFO at 62 mg/kg/day (up to a maximum daily dose of 6000 mg/day), or saline placebo, given by continuous IV infusion for 5 consecutive days. Treatment will be initiated within 24 hours after ICH symptom onset. Subjects will be stratified based on baseline ICH score (0-2 vs. 3-5) and ICH onset-to-treatment time (OTT) window (≤12h vs. >12-24h), so that the resulting randomization ratio is 1:1 within each ICH score and OTT window strata.

The main objectives are:

1. To assess whether it would be futile to move DFO forward into a Phase III trial based on the end point of good outcome (defined as dichotomized modified Rankin Scale score of 0-2 at 3 months). At the conclusion of the study, the proportion of DFO-treated subjects with a good outcome will be compared to the placebo proportion in a futility analysis. If the DFO-treated proportion is less than 12% greater than the placebo proportion, then it would be futile to move DFO forward to future Phase III testing.

2. To collect more data on treatment-related adverse events in order to ascertain that patients with ICH can tolerate this dose given over an extended 5-day duration of infusion without experiencing unreasonable neurological complications, increased mortality, or other serious adverse events related to DFO use.

Secondary and exploratory objectives include:

1- Determining the overall distribution of scores on mRS at 3 months in DFO-treated subjects, and to perform a dichotomized analysis considering the proportion of DFO- and placebo-treated subjects with mRS 0-3.

Successful completion of this study will provide a crucial "go/no-go" signal for DFO in ICH. Futility will discourage a major phase III trial, whereas non-futility will offer strong support for a phase III study to detect clinical efficacy. Results from this study can provide valuable information to guide the design and sample size estimation of a potential future Phase III trial. ICH is a frequent cause of disability and death. A successful study demonstrating the efficacy of DFO would be of considerable public health significance.

Update: Enrollment into the trial was terminated by the Data and Safety Monitoring Board because of an imbalance in subjects with reported ARDS. At the time of termination, 42 subjects had been enrolled. As a result, any formal evaluation of these objectives would be under-powered, but descriptive statistics are provided. The protocol was subsequently modified to protect subject safety, and the trial was re-initiated as iDEF (NCT02175225).

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Futility Study of Deferoxamine in Intracerebral Hemorrhage
• Actual Study Start Date: Mar 18, 2013
• Actual Primary Completion Date: Jan 15, 2014
• Actual Study Completion Date: May 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Deferoxamine Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.	Drug: Deferoxamine; Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.; Other Names: Deferoxamine Mesylate
Placebo Comparator: Normal Saline 0.9% sodium chloride	Drug: Normal saline; This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.; Other Names: 0.90% Sodium Chloride Solution

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Modified Rankin Scale (mRS) Score 0-2 [90 days]

   The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days. The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).

Secondary Outcome Measures

1. Number of Subjects With mRS Score 0-3 [90 days]

   The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days

Other Outcome Measures

1. Number of Subjects With Allergic/Anaphylactic Reaction [within 7 days or discharge]

2. Number of Patients With Hypotension [within 7 days or discharge]

3. Number of Patients With New Visual or Auditory Changes [within 7 days or discharge]

4. Number of Patients With Serious Adverse Events [90 days]

5. Number of Patients Who Died During the 90-day Study Period [90 days]

   Mortality at any time from randomization through day-90

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥ 18 and ≤ 80 years

2. The diagnosis of ICH is confirmed by brain CT scan

3. NIHSS score ≥ 6 and GCS > 6 upon presentation

4. The first dose of the study drug can be administered within 24h of ICH symptom onset

5. Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1

6. Signed and dated informed consent is obtained.

Exclusion Criteria:

1. Previous chelation therapy or known hypersensitivity to DFO products

2. Known severe iron deficiency anemia (defined as hemoglobin concentration < 7g/dL or requiring blood transfusions)

3. Abnormal renal function, defined as serum creatinine > 2 mg/dL

4. Planned surgical evacuation of ICH prior to administration of study drug (placement of a catheter for ventricular drainage is not a contraindication to enrollment)

5. Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus thrombosis

6. Infratentorial hemorrhage

7. Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and extensor motor posturing)

8. Complete unconsciousness, defined as a score of 3 on item 1a of the NIHSS (Responds only with reflex motor or autonomic effects or totally unresponsive, and flaccid)

9. Pre-existing disability, defined as pre-ICH mRS ≥ 2

10. Coagulopathy - defined as elevated aPTT or INR >1.3 upon presentation; concurrent use of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such as rivaroxaban), or low-molecular-weight heparin

11. Taking iron supplements containing ≥ 325 mg of ferrous iron, or prochlorperazine

12. Patients with heart failure taking > 500 mg of vitamin C daily

13. Known severe hearing loss

14. Known pregnancy, or positive pregnancy test, or breastfeeding

15. Patients known or suspected of not being able to comply with the study protocol due to alcoholism, drug dependency, noncompliance, living in another state or any other cause

16. Positive drug screen for cocaine upon presentation

17. Any condition which, in the judgement of the investigator, might increase the risk to the patient

18. Life expectancy of less than 90 days due to comorbid conditions

19. Concurrent participation in another research protocol for investigation of another experimental therapy

20. Indication that a new Do Not Resuscitate (DNR) or Comfort Measures Only (CMO) order will be implemented within the first 72 hours of hospitalization.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Joseph's Hospital	Phoenix	Arizona	United States	85013
2	Stanford University Hospital	Palo Alto	California	United States	94304
3	San Francisco General Hospital	San Francisco	California	United States	94110
4	Hartford Hospital	Hartford	Connecticut	United States	06107
5	Yale New Haven Hospital	New Haven	Connecticut	United States	06510
6	The University of Florida College of Medicine	Jacksonville	Florida	United States	32209
7	University of Iowa Hospital	Iowa City	Iowa	United States	52242
8	University of Maryland Medical Center	Baltimore	Maryland	United States	21201
9	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
10	Tufts Medical Center	Boston	Massachusetts	United States	02111
11	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
12	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
13	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts	United States	01655
14	Henry Ford Hospital	Detroit	Michigan	United States	48202
15	University of North Carolina Medical Center	Chapel Hill	North Carolina	United States	27514
16	Duke University Hospital	Durham	North Carolina	United States	27705
17	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
18	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
19	Oregon Health & Science University	Portland	Oregon	United States	97239
20	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104
21	Rhode Island Hospital	Providence	Rhode Island	United States	02903
22	Medical University of South Carolina	Charleston	South Carolina	United States	29425
23	The University of Texas Health Science Center	Houston	Texas	United States	77030
24	University of Virginia Health System	Charlottesville	Virginia	United States	22908
25	Harborview Medical Center	Seattle	Washington	United States	98104
26	Foothills Medical Center	Calgary	Alberta	Canada	T2N 2T9
27	Mackenzie Health Sciences Centre	Edmonton	Alberta	Canada	T6G 2B7
28	Halifax Infirmary	Halifax	Nova Scotia	Canada	B3H 3A7
29	Hôpital de l'Enfant-Jésus - CHU de Québec	Québec		Canada	G1J 1Z4

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Medical University of South Carolina
• National Institute of Neurological Disorders and Stroke (NINDS)
• Massachusetts General Hospital
• Tufts Medical Center
• University of Massachusetts, Worcester
• University of Pennsylvania
• Johns Hopkins University
• University of Maryland
• University of Virginia
• Duke University
• University of North Carolina
• University of Florida
• The Cleveland Clinic
• Henry Ford Hospital
• Ohio State University
• St. Joseph's Hospital and Medical Center, Phoenix
• University of California, San Francisco
• Oregon Health and Science University
• Yale New Haven Hospital
• University of Iowa
• Hartford Hospital
• The University of Texas Health Science Center, Houston
• Rhode Island Hospital
• Stanford University
• University of Washington
• University of Calgary
• Hopital de l'Enfant-Jesus
• University of Alberta
• Dalhousie University

Investigators

• Principal Investigator: Magdy Selim, MD, PhD, Beth Israel Deaconess Medical Center/Harvard Medical School

Study Documents (Full-Text)

None provided.

More Information

Publications

• Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009 Jun;40(6):2241-3. doi: 10.1161/STROKEAHA.108.539536. Epub 2009 Apr 16.
• Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.
• Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, Palesch Y; Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011 Nov;42(11):3067-74. doi: 10.1161/STROKEAHA.111.617589. Epub 2011 Aug 25.
• Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009 Mar;40(3 Suppl):S90-1. doi: 10.1161/STROKEAHA.108.533125. Epub 2008 Dec 8. Review.

• Responsible Party: Magdy Selim, Professor of Neurology, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT01662895
• Other Study ID Numbers: 2012P-000005; U01NS074425
• First Posted: Aug 13, 2012
• Last Update Posted: Jun 12, 2019
• Last Verified: May 1, 2019

• Keywords provided by Magdy Selim, Professor of Neurology, Beth Israel Deaconess Medical Center: Brain hemorrhage; Cerebral Hemorrhage; Deferoxamine; Hi-DEF Trial
• Additional relevant MeSH terms: Cerebral Hemorrhage; Hemorrhage; Deferoxamine

Study Results

Participant Flow

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Period Title: Overall Study
STARTED	21	21
Initiated Study Drug	21	21
COMPLETED	21	20
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Deferoxamine	Normal Saline	Total
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	Total of all reporting groups
Overall Participants	21	21	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64	64	64
Sex: Female, Male (Count of Participants)
Female	7 33.3%	9 42.9%	16 38.1%
Male	14 66.7%	12 57.1%	26 61.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 4.8%	2 9.5%	3 7.1%
Not Hispanic or Latino	20 95.2%	19 90.5%	39 92.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	4 19%	1 4.8%	5 11.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 9.5%	3 14.3%	5 11.9%
White	15 71.4%	17 81%	32 76.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Modified Rankin Scale (mRS) Score 0-2
Description	The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days. The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	20
Count of Participants [Participants]	6 28.6%	10 47.6%

2. Secondary Outcome

Title	Number of Subjects With mRS Score 0-3
Description	The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	20
Count of Participants [Participants]	12 57.1%	14 66.7%

3. Other Pre-specified Outcome

Title	Number of Subjects With Allergic/Anaphylactic Reaction
Time Frame	within 7 days or discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	0 0%	0 0%

4. Other Pre-specified Outcome

Title	Number of Patients With Hypotension
Time Frame	within 7 days or discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	1 4.8%	1 4.8%

5. Other Pre-specified Outcome

Title	Number of Patients With New Visual or Auditory Changes
Time Frame	within 7 days or discharge

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	0 0%	1 4.8%

6. Other Pre-specified Outcome

Title	Number of Patients With Serious Adverse Events
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	9 42.9%	6 28.6%

7. Other Pre-specified Outcome

Title	Number of Patients Who Died During the 90-day Study Period
Description	Mortality at any time from randomization through day-90
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	3 14.3%	0 0%

8. Post-Hoc Outcome

Title	Number of Subjects With Acute Respiratory Distress Syndrome
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Deferoxamine	Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.	0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
Measure Participants	21	21
Count of Participants [Participants]	6 28.6%	0 0%

Adverse Events

Time Frame	All adverse events (serious and non-serious) were assessed until day-7 or discharge, whichever occurs earlier, and serious adverse events until day-90 (i.e. completion of the study) or withdrawal of consent.
Arm/Group Title	Deferoxamine		Normal Saline
Arm/Group Description	Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml. Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.		0.9% sodium chloride Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
All Cause Mortality
	Deferoxamine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/21 (14.3%)		0/21 (0%)
Serious Adverse Events
	Deferoxamine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/21 (42.9%)		6/21 (28.6%)
Cardiac disorders
Bradycardia	1/21 (4.8%)	1	0/21 (0%)	0
Tachycardia	1/21 (4.8%)	1	0/21 (0%)	0
General disorders
Systemic inflammatory response syndrome	1/21 (4.8%)	1	0/21 (0%)	0
Infections and infestations
Meningitis	0/21 (0%)	0	1/21 (4.8%)	1
Pneumonia	1/21 (4.8%)	1	1/21 (4.8%)	1
Injury, poisoning and procedural complications
Fall	1/21 (4.8%)	1	0/21 (0%)	0
Investigations
Troponin increased	0/21 (0%)	0	1/21 (4.8%)	1
Metabolism and nutrition disorders
Hypophosphataemia	1/21 (4.8%)	1	0/21 (0%)	0
Nervous system disorders
Intracranial hypotension	0/21 (0%)	0	1/21 (4.8%)	1
Ischaemic cerebral infarction	0/21 (0%)	0	1/21 (4.8%)	1
Ischaemic stroke	0/21 (0%)	0	1/21 (4.8%)	1
Neurological decompensation	2/21 (9.5%)	3	1/21 (4.8%)	1
Psychiatric disorders
Delirium	1/21 (4.8%)	1	0/21 (0%)	0
Mental status changes	0/21 (0%)	0	1/21 (4.8%)	1
Renal and urinary disorders
Renal failure	2/21 (9.5%)	2	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	4/21 (19%)	4	0/21 (0%)	0
Aspiration	0/21 (0%)	0	1/21 (4.8%)	1
Hypoxia	0/21 (0%)	0	1/21 (4.8%)	1
Increased bronchial secretion	1/21 (4.8%)	1	0/21 (0%)	0
Pneumonia aspiration	0/21 (0%)	0	1/21 (4.8%)	1
Pulmonary oedema	1/21 (4.8%)	1	0/21 (0%)	0
Respiratory failure	1/21 (4.8%)	1	2/21 (9.5%)	2
Upper airway obstruction	1/21 (4.8%)	1	0/21 (0%)	0
Vascular disorders
Hypertension	1/21 (4.8%)	1	0/21 (0%)	0
Hypotension	1/21 (4.8%)	1	0/21 (0%)	0
Other (Not Including Serious) Adverse Events
	Deferoxamine		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/21 (81%)		18/21 (85.7%)
Blood and lymphatic system disorders
Anaemia	1/21 (4.8%)	1	3/21 (14.3%)	3
Coagulopathy	1/21 (4.8%)	1	1/21 (4.8%)	1
Leukocytosis	3/21 (14.3%)	3	1/21 (4.8%)	1
Thrombocytopenia	1/21 (4.8%)	1	0/21 (0%)	0
Cardiac disorders
Atrial fibrillation	1/21 (4.8%)	1	0/21 (0%)	0
Bradycardia	1/21 (4.8%)	1	1/21 (4.8%)	1
Cardiopulmonary failure	1/21 (4.8%)	1	0/21 (0%)	0
Myocardial infarction	2/21 (9.5%)	2	0/21 (0%)	0
Sinus bradycardia	1/21 (4.8%)	1	0/21 (0%)	0
Tachycardia	1/21 (4.8%)	1	1/21 (4.8%)	1
Ear and labyrinth disorders
Tinnitus	0/21 (0%)	0	1/21 (4.8%)	1
Eye disorders
Colour blindness acquired	0/21 (0%)	0	1/21 (4.8%)	1
Pupils unequal	2/21 (9.5%)	2	0/21 (0%)	0
Gastrointestinal disorders
Abdominal distension	0/21 (0%)	0	1/21 (4.8%)	1
Abdominal pain lower	0/21 (0%)	0	1/21 (4.8%)	1
Constipation	0/21 (0%)	0	1/21 (4.8%)	1
Diarrhoea	0/21 (0%)	0	1/21 (4.8%)	1
Dysphagia	1/21 (4.8%)	1	0/21 (0%)	0
Nausea	1/21 (4.8%)	1	2/21 (9.5%)	2
Vomiting	0/21 (0%)	0	1/21 (4.8%)	1
General disorders
Chest pain	0/21 (0%)	0	1/21 (4.8%)	1
Hyperthermia	1/21 (4.8%)	1	0/21 (0%)	0
Infusion site erythema	1/21 (4.8%)	1	0/21 (0%)	0
Infusion site extravasation	1/21 (4.8%)	1	0/21 (0%)	0
Infusion site inflammation	1/21 (4.8%)	1	0/21 (0%)	0
Infusion site oedema	1/21 (4.8%)	1	0/21 (0%)	0
Infusion site pain	1/21 (4.8%)	2	1/21 (4.8%)	1
Pain	1/21 (4.8%)	1	0/21 (0%)	0
Pyrexia	7/21 (33.3%)	7	6/21 (28.6%)	7
Hepatobiliary disorders
Ischaemic hepatitis	1/21 (4.8%)	1	0/21 (0%)	0
Infections and infestations
Bacteraemia	0/21 (0%)	0	1/21 (4.8%)	1
Bacterial infection	0/21 (0%)	0	1/21 (4.8%)	1
Clostridial infection	1/21 (4.8%)	1	0/21 (0%)	0
Meningitis	0/21 (0%)	0	1/21 (4.8%)	1
Pneumonia	3/21 (14.3%)	3	2/21 (9.5%)	2
Sinusitis	0/21 (0%)	0	1/21 (4.8%)	1
Urinary tract infection	4/21 (19%)	4	4/21 (19%)	4
Investigations
Alanine aminotransferase increased	0/21 (0%)	0	1/21 (4.8%)	1
Aspartate aminotransferase increased	0/21 (0%)	0	1/21 (4.8%)	1
Blood creatinine abnormal	0/21 (0%)	0	1/21 (4.8%)	1
Blood creatinine increased	1/21 (4.8%)	1	0/21 (0%)	0
Blood glucose increased	0/21 (0%)	0	1/21 (4.8%)	1
Blood iron decreased	2/21 (9.5%)	2	0/21 (0%)	0
Blood magnesium increased	1/21 (4.8%)	1	0/21 (0%)	0
Blood urea abnormal	0/21 (0%)	0	1/21 (4.8%)	1
Blood urea increased	0/21 (0%)	0	1/21 (4.8%)	1
Cardiac enzymes increased	0/21 (0%)	0	1/21 (4.8%)	1
Electrocardiogram QT prolonged	1/21 (4.8%)	1	0/21 (0%)	0
Haemoglobin decreased	0/21 (0%)	0	1/21 (4.8%)	1
International normalised ratio increased	1/21 (4.8%)	1	0/21 (0%)	0
Iron binding capacity total decreased	1/21 (4.8%)	1	0/21 (0%)	0
Prothrombin time	1/21 (4.8%)	1	0/21 (0%)	0
Prothrombin time prolonged	1/21 (4.8%)	1	0/21 (0%)	0
Renal function test abnormal	2/21 (9.5%)	2	0/21 (0%)	0
Serum ferritin abnormal	1/21 (4.8%)	1	0/21 (0%)	0
Transferrin decreased	1/21 (4.8%)	1	0/21 (0%)	0
Troponin increased	1/21 (4.8%)	1	0/21 (0%)	0
Urine analysis abnormal	1/21 (4.8%)	1	0/21 (0%)	0
White blood cell count increased	0/21 (0%)	0	1/21 (4.8%)	1
Metabolism and nutrition disorders
Electrolyte imbalance	1/21 (4.8%)	1	1/21 (4.8%)	1
Fluid overload	1/21 (4.8%)	1	0/21 (0%)	0
Hyperglycaemia	0/21 (0%)	0	1/21 (4.8%)	1
Hypernatraemia	0/21 (0%)	0	3/21 (14.3%)	3
Hypocalcaemia	1/21 (4.8%)	1	1/21 (4.8%)	1
Hypoglycaemia	0/21 (0%)	0	1/21 (4.8%)	1
Hypokalaemia	4/21 (19%)	4	1/21 (4.8%)	1
Hyponatraemia	3/21 (14.3%)	3	3/21 (14.3%)	3
Hypophosphataemia	1/21 (4.8%)	1	0/21 (0%)	0
Metabolic acidosis	1/21 (4.8%)	1	0/21 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms	1/21 (4.8%)	1	0/21 (0%)	0
Neck pain	1/21 (4.8%)	1	0/21 (0%)	0
Pain in extremity	0/21 (0%)	0	1/21 (4.8%)	1
Nervous system disorders
Brain oedema	1/21 (4.8%)	1	0/21 (0%)	0
Dysarthria	0/21 (0%)	0	1/21 (4.8%)	1
Headache	2/21 (9.5%)	2	2/21 (9.5%)	2
Hydrocephalus	1/21 (4.8%)	1	0/21 (0%)	0
Intracranial pressure increased	1/21 (4.8%)	1	0/21 (0%)	0
Intraventricular haemorrhage	1/21 (4.8%)	1	0/21 (0%)	0
Ischaemic stroke	1/21 (4.8%)	1	0/21 (0%)	0
Neurological decompensation	0/21 (0%)	0	1/21 (4.8%)	1
Somnolence	2/21 (9.5%)	2	0/21 (0%)	0
Subarachnoid haemorrhage	0/21 (0%)	0	1/21 (4.8%)	1
Tremor	0/21 (0%)	0	1/21 (4.8%)	1
Psychiatric disorders
Anxiety	0/21 (0%)	0	1/21 (4.8%)	1
Delirium	0/21 (0%)	0	1/21 (4.8%)	1
Depression	1/21 (4.8%)	1	0/21 (0%)	0
Mental status changes	1/21 (4.8%)	1	0/21 (0%)	0
Renal and urinary disorders
Haematuria	1/21 (4.8%)	1	0/21 (0%)	0
Renal failure acute	2/21 (9.5%)	2	0/21 (0%)	0
Ureteric dilatation	1/21 (4.8%)	1	0/21 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	2/21 (9.5%)	2	0/21 (0%)	0
Atelectasis	1/21 (4.8%)	1	0/21 (0%)	0
Cough	1/21 (4.8%)	1	0/21 (0%)	0
Pleural effusion	1/21 (4.8%)	1	0/21 (0%)	0
Pulmonary embolism	0/21 (0%)	0	1/21 (4.8%)	1
Pulmonary oedema	2/21 (9.5%)	2	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
Rash	0/21 (0%)	0	1/21 (4.8%)	1
Skin disorder	2/21 (9.5%)	2	0/21 (0%)	0
Vascular disorders
Hypotension	1/21 (4.8%)	1	1/21 (4.8%)	1
Phlebitis	2/21 (9.5%)	2	0/21 (0%)	0

Limitations/Caveats

The study was terminated prematurely, and only 42 subjects were enrolled. As a result, any formal evaluation of these outcomes would be under-powered. Only descriptive statistics are provided.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.