Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02175225
• Collaborator: Medical University of South Carolina (Other), National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Massachusetts General Hospital (Other), University of Massachusetts, Worcester (Other), University of Pennsylvania (Other), Johns Hopkins University (Other), Duke University (Other), University of North Carolina (Other), University of Florida (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 Health System Center for Healthcare Solutions (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), Rush University Medical Center (Other), University Hospitals Cleveland Medical Center (Other), Columbia University (Other), Weill Medical College of Cornell University (Other), NYU Langone Health (Other), Mount Sinai Hospital, New York (Other), Loyola University (Other)
• Enrollment: 294
• Locations: 28
• Arms: 2
• Actual Duration (Months): 43.9
• Patients Per Site: 10.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The investigators hypothesize that treatment with the iron chelator, Deferoxamine Mesylate, improves the outcome of patients with brain hemorrhage.

The 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 intracerebral hemorrhage.

Condition or Disease	Intervention/Treatment	Phase
Intracerebral Hemorrhage	Drug: Deferoxamine Mesylate; Drug: Placebo (for Deferoxamine Mesylate)	Phase 2

Detailed Description

This is a prospective, multi-center, double-blind, randomized, placebo-controlled, phase-II clinical trial.

Subjects will be randomized to either deferoxamine mesylate (DFO) at 32 mg/kg/day (up to a maximum daily dose of 6000 mg/day), or saline placebo, given by IV infusion for 3 consecutive days.

Treatment will be initiated within 24 hours after ICH symptom onset. Randomization will control baseline imbalances associated with baseline ICH score, ICH onset-to-treatment time (OTT), ICH volume, baseline NIHSS score, and warfarin use.

All subjects will be followed for 6 months and will receive standard of care therapy while participating in the study.

Throughout the study, we will continue to assess the safety of DFO. At the conclusion of the study, the proportion of DFO-treated subjects with a good clinical outcome at 3 months (defined as modified Rankin Scale (mRS) score of 0-2) will be compared to the placebo proportion in a futility analysis to determine if it is futile to move DFO forward to Phase III efficacy evaluation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 294 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Study of Deferoxamine Mesylate in Intracerebral Hemorrhage
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Feb 10, 2018
• Actual Study Completion Date: May 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Deferoxamine Mesylate Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days	Drug: Deferoxamine Mesylate
Placebo Comparator: Normal Saline Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days	Drug: Placebo (for Deferoxamine Mesylate)

Outcome Measures

Primary Outcome Measures

1. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days [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 mRS ranges from 0 to 6, with higher scores indicating worse outcome.

2. Number of Subjects Experiencing Serious Adverse Events [90 days]

   Number of subjects experiencing Serious adverse events at any time from randomization through day 90

3. Number of Subjects With Serious Adverse Events Within 7 Days [7 days]

   Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization

Secondary Outcome Measures

1. Proportion of Patients With mRS Score 0-3 at 90 Days [90 days]

   Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 90 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Although mRS 0-3 is less favorable than the primary outcome of mRS 0-2, it would still be a desirable effect in patients with ICH given that no treatments exist to reduce disability.

2. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 180 Days [180 days]

   Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

3. Proportion of Patients With Modified Rankin Scale (mRS) Score 0-3 at 180 Days [180 days]

   Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.

4. Proportion of Subjects With Good Outcome (mRS 0-2) in the Early vs. Delayed Treatment Time Windows [90 days]

   Analyses will be expanded to include an interaction between treatment and OTT window and the magnitude of the treatment effect, and corresponding confidence interval, will be estimated for each time window (<12 hours vs. >/= 12 hours) in order to explore the presence of a differential treatment effect in the OTT windows.

Other Outcome Measures

1. Ordinal Distribution of Scores on mRS at Day 90 [90 days]

   The overall ordinal distribution of scores on mRS at 90 days in DFO- and placebo-treated subjects will be determined.

2. Ordinal Distribution of Scores on mRS at 180 Days [180 days]

   The overall ordinal distribution of scores on mRS at 180 days in DFO- and placebo-treated subjects will be determined.

3. Adverse Event of Special Interest: Number of Patients With Allergic Reactions (During Infusion of Study Drug) [during the study infusion]

   Adverse event of special interest: anaphylaxis at any time during the study infusion

4. Adverse Event of Special Interest: Number of Patients With Hypotension [during the study infusion]

   Hypotension requiring medical intervention at any time during the study infusion that could not be explained by other causes

5. Adverse Event of Special Interest: Number of Patients With New Visual or Auditory Changes [after initiation of study infusion]

   Adverse event of special interest: development of new and unexplained visual or auditory changes after initiation of the study infusion

6. Adverse Event of Special Interest: Number of Patients With Respiratory Compromise [7 days]

   Adverse event of special interest: Respiratory compromise of any cause, including acute respiratory distress syndrome, in hospital until day 7 or discharge [whichever was earlier]

7. Number of Patients With Symptomatic Cerebral Edema [7 days]

   Edema accompanied by an unexplained increase of more than four points on the US National Institutes of Health Stroke Scale or a decrease of more than two points in Glasgow Coma Scale score during the first week after the intracerebral haemorrhage.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age ≥ 18 and ≤ 80 years

• The diagnosis of ICH is confirmed by brain CT scan

• NIHSS score ≥6 and GCS >6 upon presentation

• The first dose of the study drug is expected to be administered within 24h of ICH symptom onset

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

• Signed and dated informed consent is obtained.

Exclusion Criteria:

• Previous chelation therapy or known hypersensitivity to DFO products

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

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

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

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

• Infratentorial hemorrhage

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

• 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)

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

• 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 apixaban), or low-molecular-weight heparin

• Patients with confirmed aspiration, pneumonia, or evident bilateral pulmonary infiltrates on chest x-ray or CT scan prior to enrollment

• Patients with significant respiratory disease such as chronic obstructive pulmonary disease, pulmonary fibrosis, or any use (chronic or intermittent) of inhaled O2 at home

• FiO2 >0.35 (>4 L/min) prior to enrollment

• Sepsis (present source of infection ± lactic acidosis); Systemic Inflammatory Response Syndrome (Temp >100.4F or <96.8F; Heart rate >90; Respiratory rate >20 or PaCo2 <32 mmHg; WBC >12, <4, or bands >10%); or shock (SBP <90 mmHg) at presentation

• The presence of 4 or more of the following risk modifiers for ARDS prior to enrollment:

1. Tachypnea (respiratory rate >30)

2. SpO2 <95%

3. Obesity (BMI >30)

4. Acidosis (pH <7.35)

5. Hypoalbuminemia (albumin <3.5 g/dL)

6. Concurrent use of chemotherapy

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

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

• Known severe hearing loss

• Known pregnancy, or positive pregnancy test, or breastfeeding

• Positive drug screen for cocaine upon presentation

• 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

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

• Life expectancy of less than 90 days due to co-morbid conditions

• Concurrent participation in another research protocol for investigation of another experimental therapy

• Indication that a new 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 / Barrow Neurological Institute	Phoenix	Arizona	United States
2	Stanford University Medical Center	Palo Alto	California	United States
3	San Francisco General Hospital	San Francisco	California	United States
4	Yale New Haven Hospital	New Haven	Connecticut	United States
5	University of Florida	Jacksonville	Florida	United States
6	Loyola University Medical Center	Chicago	Illinois	United States
7	RUSH University Medical Center	Chicago	Illinois	United States
8	University of Iowa Medical Center	Iowa City	Iowa	United States
9	Johns Hopkins Hospital	Baltimore	Maryland	United States
10	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States
11	UMass Memorial Medical Center	Worcester	Massachusetts	United States
12	Henry Ford Hospital	Detroit	Michigan	United States
13	Columbia University	New York	New York	United States
14	Mount Sinai Hospital	New York	New York	United States
15	NYU Langone Medical Center	New York	New York	United States
16	Weill Medical College of Cornell University	New York	New York	United States
17	University of North Carolina Medical Center	Chapel Hill	North Carolina	United States
18	Duke University Medical Center	Durham	North Carolina	United States
19	University Hospital Case Medical Center	Cleveland	Ohio	United States
20	The Ohio State University Medical Center	Columbus	Ohio	United States
21	Oregon Health & Science University Medical Center	Portland	Oregon	United States
22	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States
23	Rhode Island Hospital	Providence	Rhode Island	United States
24	Medical University of South Carolina	Charleston	South Carolina	United States
25	University of Texas Health Sciences Center	Houston	Texas	United States
26	Foothills Hospital - University of Calgary	Calgary	Alberta	Canada
27	University of Alberta - Mackenzie Health Sciences Centre	Edmonton	Alberta	Canada
28	CHU de Québec - Hôpital de l'Enfant-Jésus	Québec		Canada

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center
• Medical University of South Carolina
• National Institute of Neurological Disorders and Stroke (NINDS)
• Massachusetts General Hospital
• University of Massachusetts, Worcester
• University of Pennsylvania
• Johns Hopkins University
• Duke University
• University of North Carolina
• University of Florida
• 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 Health System Center for Healthcare Solutions
• 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
• Rush University Medical Center
• University Hospitals Cleveland Medical Center
• Columbia University
• Weill Medical College of Cornell University
• NYU Langone Health
• Mount Sinai Hospital, New York
• Loyola University

Investigators

• Study Chair: Magdy Selim, MD, PhD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol - May 15, 2014
• Statistical Analysis Plan - Jul 11, 2018

More Information

Publications

• Hatakeyama T, Okauchi M, Hua Y, Keep RF, Xi G. Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats. Transl Stroke Res. 2013 Oct;4(5):546-53. doi: 10.1007/s12975-013-0270-5.
• Okauchi M, Hua Y, Keep RF, Morgenstern LB, Schallert T, Xi G. Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration. Stroke. 2010 Feb;41(2):375-82. doi: 10.1161/STROKEAHA.109.569830. Epub 2009 Dec 31.
• 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.
• Sonni S, Lioutas VA, Selim MH. New avenues for treatment of intracranial hemorrhage. Curr Treat Options Cardiovasc Med. 2014 Jan;16(1):277. doi: 10.1007/s11936-013-0277-y.
• Xie Q, Gu Y, Hua Y, Liu W, Keep RF, Xi G. Deferoxamine attenuates white matter injury in a piglet intracerebral hemorrhage model. Stroke. 2014 Jan;45(1):290-2. doi: 10.1161/STROKEAHA.113.003033. Epub 2013 Oct 30.
• Yeatts SD, Palesch YY, Moy CS, Selim M. High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Neurocrit Care. 2013 Oct;19(2):257-66. doi: 10.1007/s12028-013-9861-y.

• Responsible Party: Magdy Selim, MD, PhD, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02175225
• Other Study ID Numbers: 2012P000005; U01NS074425
• First Posted: Jun 26, 2014
• Last Update Posted: May 30, 2019
• Last Verified: May 1, 2019

• Keywords provided by Magdy Selim, MD, PhD, Beth Israel Deaconess Medical Center: Brain hemorrhage; Cerebral hemorrhage; Bleeding in the brain; Deferoxamine; iDEF trial
• Additional relevant MeSH terms: Cerebral Hemorrhage; Hemorrhage; Deferoxamine

Study Results

Participant Flow

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Period Title: Overall Study
STARTED	145	149
Initiated Study Drug	144	147
90 Day Outcome Obtained	140	143
180 Day Outcome Obtained	135	135
COMPLETED	137	138
NOT COMPLETED	8	11

Baseline Characteristics

Arm/Group Title	Deferoxamine Mesylate	Normal Saline	Total
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)	Total of all reporting groups
Overall Participants	144	147	291
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	59	62	61
Sex: Female, Male (Count of Participants)
Female	56 38.9%	56 38.1%	112 38.5%
Male	88 61.1%	91 61.9%	179 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 14.6%	27 18.4%	48 16.5%
Not Hispanic or Latino	123 85.4%	120 81.6%	243 83.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.4%	0 0%	2 0.7%
Asian	25 17.4%	12 8.2%	37 12.7%
Native Hawaiian or Other Pacific Islander	3 2.1%	1 0.7%	4 1.4%
Black or African American	31 21.5%	33 22.4%	64 22%
White	81 56.3%	100 68%	181 62.2%
More than one race	1 0.7%	0 0%	1 0.3%
Unknown or Not Reported	1 0.7%	1 0.7%	2 0.7%
Medical history: Hypertension (Count of Participants)
Count of Participants [Participants]	113 78.5%	124 84.4%	237 81.4%
Medical history: Diabetes mellitus (Count of Participants)
Count of Participants [Participants]	32 22.2%	43 29.3%	75 25.8%
Medical history: Cardiac disease (Count of Participants)
Count of Participants [Participants]	14 9.7%	15 10.2%	29 10%
Medical history: Pulmonary disease (Count of Participants)
Count of Participants [Participants]	31 21.5%	26 17.7%	57 19.6%
Medical history: Previous ischemic stroke or transient ischemic attack (Count of Participants)
Count of Participants [Participants]	10 6.9%	16 10.9%	26 8.9%
Medical history: Previous intracerebral hemorrhage (Count of Participants)
Count of Participants [Participants]	7 4.9%	3 2%	10 3.4%
Location of intracerebral hemorrhage (Count of Participants)
Lobar	26 18.1%	33 22.4%	59 20.3%
Deep (thalamic)	45 31.3%	61 41.5%	106 36.4%
Deep (non-thalamic)	73 50.7%	53 36.1%	126 43.3%
Intraventricular hemorrhage present (Count of Participants)
Count of Participants [Participants]	47 32.6%	62 42.2%	109 37.5%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
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 mRS ranges from 0 to 6, with higher scores indicating worse outcome.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	140	143
Count of Participants [Participants]	48 33.3%	47 32%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments	The alternative hypothesis, reflecting futility, is that the absolute treatment effect is less than 12% in favor of deferoxamine. In accordance with the futility design, futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if the upper bound on the risk difference was less than 12% in favour of deferoxamine mesylate, this would be considered evidence of futility.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.006
	Confidence Interval	(1-Sided) 90%; to 0.068
	Parameter Dispersion	Type: Value:
	Estimation Comments	Futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if UCB was less than 12% in favour of deferoxamine mesylate, this is considered evidence of futility.

2. Primary Outcome

Title	Number of Subjects Experiencing Serious Adverse Events
Description	Number of subjects experiencing Serious adverse events at any time from randomization through day 90
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	39 27.1%	49 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Subjects With Serious Adverse Events Within 7 Days
Description	Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	24 16.7%	26 17.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Proportion of Patients With mRS Score 0-3 at 90 Days
Description	Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 90 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome. Although mRS 0-3 is less favorable than the primary outcome of mRS 0-2, it would still be a desirable effect in patients with ICH given that no treatments exist to reduce disability.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	140	143
Count of Participants [Participants]	91 63.2%	82 55.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments	The alternative hypothesis, reflecting futility, is that the absolute treatment effect is less than 13% in favor of deferoxamine. In accordance with the futility design, futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if the upper bound on the risk difference was less than13% in favor of deferoxamine mesylate, this would be considered evidence of futility.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.062
	Confidence Interval	(1-Sided) 90%; to 0.121
	Parameter Dispersion	Type: Value:
	Estimation Comments	Futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference[AARD]); if UCB was less than 12% in favour of deferoxamine mesylate, this is considered evidence of futility.

5. Secondary Outcome

Title	Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 180 Days
Description	Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	135	135
Count of Participants [Participants]	61 42.4%	48 32.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments	The alternative hypothesis, reflecting futility, is that the absolute treatment effect is less than 12% in favor of deferoxamine. In accordance with the futility design, futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if the upper bound on the risk difference was less than 12% in favour of deferoxamine mesylate, this would be considered evidence of futility.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.086
	Confidence Interval	(1-Sided) 90%; to 0.156
	Parameter Dispersion	Type: Value:
	Estimation Comments	Futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if UCB was less than 12% in favour of deferoxamine mesylate, this is considered evidence of futility.

6. Secondary Outcome

Title	Proportion of Patients With Modified Rankin Scale (mRS) Score 0-3 at 180 Days
Description	Another measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-3 at 180 days. The mRS ranges from 0 to 6, with higher scores indicating worse outcome.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	135	135
Count of Participants [Participants]	97 67.4%	92 62.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments	The alternative hypothesis, reflecting futility, is that the absolute treatment effect is less than 13% in favor of deferoxamine. In accordance with the futility design, futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if the upper bound on the risk difference was less than 13% in favour of deferoxamine mesylate, this would be considered evidence of futility.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.018
	Confidence Interval	(1-Sided) 90%; to 0.029
	Parameter Dispersion	Type: Value:
	Estimation Comments	Futility was evaluated via the one-sided 90% upper confidence bound (90% UCB) of the treatment effect (absolute adjusted risk difference [AARD]); if UCB was less than 13% in favour of deferoxamine mesylate, this is considered evidence of futility.

7. Secondary Outcome

Title	Proportion of Subjects With Good Outcome (mRS 0-2) in the Early vs. Delayed Treatment Time Windows
Description	Analyses will be expanded to include an interaction between treatment and OTT window and the magnitude of the treatment effect, and corresponding confidence interval, will be estimated for each time window (<12 hours vs. >/= 12 hours) in order to explore the presence of a differential treatment effect in the OTT windows.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach. Subgroup analysis by Onset to treatment time window (<=12 hours vs >12 hours)

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	140	143
Onset to treatment time <=12 hours	15 10.4%	19 12.9%
Onset to treatment time >12 hours	33 22.9%	28 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments	The p value reflects the significance of the interaction term between treatment and onset to treatment time.
	Method	Regression, Logistic
	Comments

8. Other Pre-specified Outcome

Title	Ordinal Distribution of Scores on mRS at Day 90
Description	The overall ordinal distribution of scores on mRS at 90 days in DFO- and placebo-treated subjects will be determined.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	140	143
mRS 0	6 4.2%	4 2.7%
mRS 1	13 9%	12 8.2%
mRS 2	29 20.1%	31 21.1%
mRS 3	43 29.9%	35 23.8%
mRS 4	33 22.9%	43 29.3%
mRS 5	6 4.2%	7 4.8%
mRS 6	10 6.9%	11 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimation parameter is the adjusted common odds ratio.

9. Other Pre-specified Outcome

Title	Ordinal Distribution of Scores on mRS at 180 Days
Description	The overall ordinal distribution of scores on mRS at 180 days in DFO- and placebo-treated subjects will be determined.
Time Frame	180 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated. Complete case analysis was planned as the primary analytic approach.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	135	135
mRS 0	10 6.9%	5 3.4%
mRS 1	18 12.5%	16 10.9%
mRS 2	33 22.9%	27 18.4%
mRS 3	36 25%	44 29.9%
mRS 4	22 15.3%	24 16.3%
mRS 5	4 2.8%	7 4.8%
mRS 6	12 8.3%	12 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Other Pre-specified Outcome

Title	Adverse Event of Special Interest: Number of Patients With Allergic Reactions (During Infusion of Study Drug)
Description	Adverse event of special interest: anaphylaxis at any time during the study infusion
Time Frame	during the study infusion

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	3 2.1%	0 0%

11. Other Pre-specified Outcome

Title	Adverse Event of Special Interest: Number of Patients With Hypotension
Description	Hypotension requiring medical intervention at any time during the study infusion that could not be explained by other causes
Time Frame	during the study infusion

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	1 0.7%	2 1.4%

12. Other Pre-specified Outcome

Title	Adverse Event of Special Interest: Number of Patients With New Visual or Auditory Changes
Description	Adverse event of special interest: development of new and unexplained visual or auditory changes after initiation of the study infusion
Time Frame	after initiation of study infusion

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	3 2.1%	4 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.0 to 14.97
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval is exact (rather than asymptotic) due to small number of events.

13. Other Pre-specified Outcome

Title	Adverse Event of Special Interest: Number of Patients With Respiratory Compromise
Description	Adverse event of special interest: Respiratory compromise of any cause, including acute respiratory distress syndrome, in hospital until day 7 or discharge [whichever was earlier]
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
All cause	20 13.9%	23 15.6%
Cause by acute respiratory distress syndrome	2 1.4%	1 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval constructed only for all cause owing to small number of events caused by acute respiratory distress syndrome.

14. Other Pre-specified Outcome

Title	Number of Patients With Symptomatic Cerebral Edema
Description	Edema accompanied by an unexplained increase of more than four points on the US National Institutes of Health Stroke Scale or a decrease of more than two points in Glasgow Coma Scale score during the first week after the intracerebral haemorrhage.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

Per the SAP, the target population is the modified intention-to-treat population, including only subjects in whom study infusion is initiated.

Arm/Group Title	Deferoxamine Mesylate	Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate	Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
Measure Participants	144	147
Count of Participants [Participants]	9 6.3%	5 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Deferoxamine Mesylate, Normal Saline
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.84
	Confidence Interval	(2-Sided) 95%; 0.63 to 5.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All-cause mortality was collected until 180 days post-randomization. Serious adverse events were collected until 90 days post-randomization. Non-serious adverse events were collected until day 7 post-randomization or hospital discharge, whichever is earlier.
Adverse Event Reporting Description	Adverse events were classified with MedDRA v15 combined with Principal Investigator preferred adjustments.
Arm/Group Title	Deferoxamine Mesylate		Normal Saline
Arm/Group Description	Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days Deferoxamine Mesylate		Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days Placebo (for Deferoxamine Mesylate)
All Cause Mortality
	Deferoxamine Mesylate		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/144 (8.3%)		12/147 (8.2%)
Serious Adverse Events
	Deferoxamine Mesylate		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/144 (27.1%)		50/147 (34%)
Cardiac disorders
Arrhythmia	1/144 (0.7%)	1	1/147 (0.7%)	2
Cardiac arrest	1/144 (0.7%)	1	2/147 (1.4%)	2
Myocardial infarction	1/144 (0.7%)	1	1/147 (0.7%)	1
Gastrointestinal disorders
Constipation	0/144 (0%)	0	1/147 (0.7%)	1
Gastrointestinal haemorrhage	0/144 (0%)	0	2/147 (1.4%)	3
Haematemesis	0/144 (0%)	0	2/147 (1.4%)	2
Ileus	0/144 (0%)	0	1/147 (0.7%)	1
Oedema mouth	1/144 (0.7%)	1	0/147 (0%)	0
Retroperitoneal haemorrhage	0/144 (0%)	0	1/147 (0.7%)	1
Vomiting	0/144 (0%)	0	1/147 (0.7%)	1
General disorders
Chest pain	1/144 (0.7%)	1	0/147 (0%)	0
Systemic inflammatory response syndrome	1/144 (0.7%)	1	0/147 (0%)	0
Hepatobiliary disorders
Acute hepatic failure	0/144 (0%)	0	1/147 (0.7%)	1
Immune system disorders
Hypersensitivity	1/144 (0.7%)	1	0/147 (0%)	0
Infections and infestations
Bacteraemia	2/144 (1.4%)	2	1/147 (0.7%)	1
Clostridium difficile colitis	1/144 (0.7%)	1	0/147 (0%)	0
Pneumonia	2/144 (1.4%)	2	4/147 (2.7%)	4
Sepsis	3/144 (2.1%)	3	2/147 (1.4%)	2
Septic shock	1/144 (0.7%)	1	0/147 (0%)	0
Tracheobronchitis	0/144 (0%)	0	1/147 (0.7%)	1
Urinary tract infection	2/144 (1.4%)	2	3/147 (2%)	3
Injury, poisoning and procedural complications
Fall	0/144 (0%)	0	1/147 (0.7%)	1
Rib fracture	0/144 (0%)	0	1/147 (0.7%)	1
Wound decomposition	1/144 (0.7%)	1	0/147 (0%)	0
Investigations
Anaemia	1/144 (0.7%)	1	0/147 (0%)	0
Cardiac enzymes increased	0/144 (0%)	0	1/147 (0.7%)	1
Hyponatraemia	1/144 (0.7%)	1	0/147 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/144 (0%)	0	1/147 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma	0/144 (0%)	0	1/147 (0.7%)	1
Nervous system disorders
Autonomic nervous system imbalance	1/144 (0.7%)	1	0/147 (0%)	0
Brain herniation	4/144 (2.8%)	4	2/147 (1.4%)	2
Brain midline shift	1/144 (0.7%)	1	0/147 (0%)	0
Brain oedema	5/144 (3.5%)	5	2/147 (1.4%)	2
CNS ventriculitis	2/144 (1.4%)	2	1/147 (0.7%)	1
Cerebral haemorrhage	2/144 (1.4%)	2	2/147 (1.4%)	2
Cerebral hematoma expansion	1/144 (0.7%)	1	2/147 (1.4%)	2
Convulsion	2/144 (1.4%)	2	1/147 (0.7%)	1
Hydrocephalus	4/144 (2.8%)	4	1/147 (0.7%)	1
Hypoaesthesia	0/144 (0%)	0	1/147 (0.7%)	1
Intracranial pressure increased	2/144 (1.4%)	2	2/147 (1.4%)	2
Ischaemic stroke	1/144 (0.7%)	1	2/147 (1.4%)	2
Neurological decompensation	1/144 (0.7%)	2	4/147 (2.7%)	4
Syncope/Presyncope	0/144 (0%)	0	2/147 (1.4%)	2
Psychiatric disorders
Alcohol withdrawal syndrome	0/144 (0%)	0	1/147 (0.7%)	1
Mental status changes	0/144 (0%)	0	1/147 (0.7%)	1
Renal and urinary disorders
Haematuria	1/144 (0.7%)	1	0/147 (0%)	0
Renal failure acute	0/144 (0%)	0	1/147 (0.7%)	1
Reproductive system and breast disorders
Pelvic pain	0/144 (0%)	0	1/147 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/144 (0%)	0	1/147 (0.7%)	1
Asthma	2/144 (1.4%)	2	0/147 (0%)	0
Bronchial obstruction	0/144 (0%)	0	1/147 (0.7%)	1
Hypoxia	0/144 (0%)	0	1/147 (0.7%)	1
Lung consolidation	0/144 (0%)	0	1/147 (0.7%)	1
Pneumonia aspiration	4/144 (2.8%)	4	4/147 (2.7%)	4
Pulmonary embolism	4/144 (2.8%)	4	1/147 (0.7%)	1
Pulmonary oedema	1/144 (0.7%)	1	2/147 (1.4%)	2
Respiratory distress	0/144 (0%)	0	1/147 (0.7%)	1
Respiratory failure	2/144 (1.4%)	3	4/147 (2.7%)	4
Skin and subcutaneous tissue disorders
Skin ulcer	1/144 (0.7%)	1	0/147 (0%)	0
Surgical and medical procedures
Withdrawal of life support	1/144 (0.7%)	1	2/147 (1.4%)	2
Vascular disorders
Deep vein thrombosis	3/144 (2.1%)	3	3/147 (2%)	3
Hypertension	1/144 (0.7%)	1	0/147 (0%)	0
Hypotension	1/144 (0.7%)	1	1/147 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Deferoxamine Mesylate		Normal Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	107/144 (74.3%)		114/147 (77.6%)
Cardiac disorders
Arrhythmia	11/144 (7.6%)	12	11/147 (7.5%)	13
Myocardial infarction	0/144 (0%)	0	1/147 (0.7%)	1
Myocardial ischaemia	0/144 (0%)	0	1/147 (0.7%)	1
Ear and labyrinth disorders
Ear pain	1/144 (0.7%)	1	0/147 (0%)	0
Hearing impaired	1/144 (0.7%)	1	1/147 (0.7%)	1
Tinnitus	1/144 (0.7%)	1	0/147 (0%)	0
Endocrine disorders
Goitre	1/144 (0.7%)	1	0/147 (0%)	0
Inappropriate antidiuretic hormone secretion	0/144 (0%)	0	1/147 (0.7%)	1
Eye disorders
Blindness	0/144 (0%)	0	1/147 (0.7%)	1
Colour blindness	1/144 (0.7%)	1	0/147 (0%)	0
Conjunctivitis	1/144 (0.7%)	1	1/147 (0.7%)	1
Diplopia	0/144 (0%)	0	1/147 (0.7%)	1
Eye pain	0/144 (0%)	0	1/147 (0.7%)	1
Gaze palsy	1/144 (0.7%)	1	0/147 (0%)	0
Pupils unequal	1/144 (0.7%)	1	2/147 (1.4%)	2
Scleral oedema	0/144 (0%)	0	1/147 (0.7%)	1
Gastrointestinal disorders
Abdominal distension	1/144 (0.7%)	1	0/147 (0%)	0
Abdominal pain	1/144 (0.7%)	1	0/147 (0%)	0
Anorectal disorder	1/144 (0.7%)	1	0/147 (0%)	0
Constipation	6/144 (4.2%)	6	10/147 (6.8%)	10
Diarrhoea	2/144 (1.4%)	2	3/147 (2%)	3
Dry mouth	1/144 (0.7%)	1	0/147 (0%)	0
Dysphagia	0/144 (0%)	0	1/147 (0.7%)	1
Ileus	1/144 (0.7%)	1	1/147 (0.7%)	1
Lip swelling	1/144 (0.7%)	1	0/147 (0%)	0
Nausea	5/144 (3.5%)	5	3/147 (2%)	3
Reflux gastritis	0/144 (0%)	0	1/147 (0.7%)	1
Swollen tongue	1/144 (0.7%)	1	0/147 (0%)	0
Vomiting	13/144 (9%)	13	6/147 (4.1%)	6
General disorders
Chest pain	3/144 (2.1%)	3	1/147 (0.7%)	1
Discomfort	1/144 (0.7%)	1	0/147 (0%)	0
Fatigue	1/144 (0.7%)	1	0/147 (0%)	0
Inflammation	1/144 (0.7%)	1	0/147 (0%)	0
Infusion site extravasation	2/144 (1.4%)	2	5/147 (3.4%)	6
Infusion site pain	2/144 (1.4%)	2	0/147 (0%)	0
Injection site irritation	1/144 (0.7%)	1	0/147 (0%)	0
Injection site reaction	1/144 (0.7%)	1	0/147 (0%)	0
Nodule	1/144 (0.7%)	1	0/147 (0%)	0
Oedema	1/144 (0.7%)	1	0/147 (0%)	0
Oedema peripheral	0/144 (0%)	0	1/147 (0.7%)	1
Pain	0/144 (0%)	0	1/147 (0.7%)	1
Pyrexia	17/144 (11.8%)	17	16/147 (10.9%)	17
Systemic inflammatory response syndrome	1/144 (0.7%)	1	0/147 (0%)	0
Infections and infestations
Bacteraemia	1/144 (0.7%)	1	0/147 (0%)	0
Cellulitis	1/144 (0.7%)	1	1/147 (0.7%)	1
Otitis media	1/144 (0.7%)	1	0/147 (0%)	0
Pneumonia	7/144 (4.9%)	7	3/147 (2%)	3
Sinusitis	2/144 (1.4%)	2	0/147 (0%)	0
Skin candida	1/144 (0.7%)	1	0/147 (0%)	0
Tinea pedis	0/144 (0%)	0	1/147 (0.7%)	1
Tracheobronchitis	0/144 (0%)	0	1/147 (0.7%)	1
Urinary tract infection	18/144 (12.5%)	18	22/147 (15%)	22
Injury, poisoning and procedural complications
Anaphylactic transfusion reaction	0/144 (0%)	0	1/147 (0.7%)	1
Fall	2/144 (1.4%)	2	1/147 (0.7%)	1
Investigations
Activated partial thromboplastin time prolonged	1/144 (0.7%)	1	0/147 (0%)	0
Anaemia	3/144 (2.1%)	3	2/147 (1.4%)	2
Blood creatinine increased	4/144 (2.8%)	4	6/147 (4.1%)	6
Blood glucose increased	1/144 (0.7%)	1	0/147 (0%)	0
Blood potassium decreased	1/144 (0.7%)	1	0/147 (0%)	0
Blood urea increased	0/144 (0%)	0	2/147 (1.4%)	2
Cardiac enzymes increased	1/144 (0.7%)	1	2/147 (1.4%)	2
Coagulopathy	0/144 (0%)	0	1/147 (0.7%)	1
Hepatic enzyme increased	0/144 (0%)	0	4/147 (2.7%)	4
Hyperglycaemia	7/144 (4.9%)	7	7/147 (4.8%)	7
Hypernatraemia	5/144 (3.5%)	5	1/147 (0.7%)	1
Hyperphosphataemia	1/144 (0.7%)	1	0/147 (0%)	0
Hypoalbuminaemia	0/144 (0%)	0	1/147 (0.7%)	1
Hypocalcaemia	3/144 (2.1%)	3	3/147 (2%)	3
Hypokalaemia	11/144 (7.6%)	11	4/147 (2.7%)	4
Hypomagnesaemia	2/144 (1.4%)	2	2/147 (1.4%)	2
Hyponatraemia	5/144 (3.5%)	5	5/147 (3.4%)	5
Hypophosphataemia	7/144 (4.9%)	7	4/147 (2.7%)	4
International normalised ratio increased	1/144 (0.7%)	1	0/147 (0%)	0
Laboratory test abnormal	0/144 (0%)	0	1/147 (0.7%)	2
Leukocytosis	5/144 (3.5%)	5	5/147 (3.4%)	5
Monocyte count	0/144 (0%)	0	1/147 (0.7%)	1
Prothrombin time prolonged	1/144 (0.7%)	1	0/147 (0%)	0
Pyuria	1/144 (0.7%)	1	0/147 (0%)	0
Rubulavirus test positive	1/144 (0.7%)	1	0/147 (0%)	0
Thrombocytopenia	0/144 (0%)	0	1/147 (0.7%)	1
Urine output decreased	0/144 (0%)	0	1/147 (0.7%)	1
Metabolism and nutrition disorders
Dehydration	1/144 (0.7%)	1	1/147 (0.7%)	1
Diabetes mellitus	2/144 (1.4%)	2	0/147 (0%)	0
Fluid retention	0/144 (0%)	0	1/147 (0.7%)	1
Gout	1/144 (0.7%)	1	2/147 (1.4%)	2
Hypovolaemia	0/144 (0%)	0	1/147 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/144 (0.7%)	1	0/147 (0%)	0
Back pain	0/144 (0%)	0	1/147 (0.7%)	1
Chondrocalcinosis pyrophosphate	1/144 (0.7%)	1	0/147 (0%)	0
Joint effusion	1/144 (0.7%)	1	0/147 (0%)	0
Joint swelling	1/144 (0.7%)	1	0/147 (0%)	0
Limb discomfort	0/144 (0%)	0	1/147 (0.7%)	1
Muscle spasms	1/144 (0.7%)	1	1/147 (0.7%)	1
Musculoskeletal pain	0/144 (0%)	0	2/147 (1.4%)	2
Neck pain	0/144 (0%)	0	2/147 (1.4%)	2
Pain in extremity	2/144 (1.4%)	2	1/147 (0.7%)	1
Pain in jaw	0/144 (0%)	0	1/147 (0.7%)	1
Nervous system disorders
Brain midline shift	1/144 (0.7%)	1	0/147 (0%)	0
Brain oedema	0/144 (0%)	0	1/147 (0.7%)	1
Cerebral haemorrhage	1/144 (0.7%)	1	1/147 (0.7%)	1
Cerebral hematoma expansion	1/144 (0.7%)	1	3/147 (2%)	3
Convulsion	4/144 (2.8%)	4	6/147 (4.1%)	6
Encephalopathy	1/144 (0.7%)	1	0/147 (0%)	0
Headache	7/144 (4.9%)	7	8/147 (5.4%)	8
Hemiparesis	0/144 (0%)	0	1/147 (0.7%)	1
Hemiplegia	0/144 (0%)	0	1/147 (0.7%)	1
Hydrocephalus	0/144 (0%)	0	5/147 (3.4%)	5
Intracranial aneurysm	0/144 (0%)	0	1/147 (0.7%)	1
Intracranial pressure increased	2/144 (1.4%)	2	3/147 (2%)	3
Ischaemic stroke	3/144 (2.1%)	3	2/147 (1.4%)	2
Lethargy	1/144 (0.7%)	1	0/147 (0%)	0
Neurological decompensation	1/144 (0.7%)	1	2/147 (1.4%)	2
Paraesthesia	1/144 (0.7%)	1	0/147 (0%)	0
Sensory loss	0/144 (0%)	0	1/147 (0.7%)	1
Somnolence	1/144 (0.7%)	1	4/147 (2.7%)	5
Subarachnoid haemorrhage	0/144 (0%)	0	1/147 (0.7%)	1
Syncope/Presyncope	1/144 (0.7%)	1	2/147 (1.4%)	2
Tremor	0/144 (0%)	0	1/147 (0.7%)	1
Visual field defect	0/144 (0%)	0	3/147 (2%)	3
Psychiatric disorders
Agitation	13/144 (9%)	15	8/147 (5.4%)	9
Alcohol withdrawal syndrome	1/144 (0.7%)	1	1/147 (0.7%)	1
Anxiety	3/144 (2.1%)	3	1/147 (0.7%)	1
Confusional state	1/144 (0.7%)	1	0/147 (0%)	0
Delirium	7/144 (4.9%)	7	5/147 (3.4%)	5
Depression	0/144 (0%)	0	1/147 (0.7%)	1
Insomnia	2/144 (1.4%)	2	2/147 (1.4%)	2
Renal and urinary disorders
Dysuria	0/144 (0%)	0	1/147 (0.7%)	1
Haematuria	1/144 (0.7%)	1	0/147 (0%)	0
Incontinence	0/144 (0%)	0	1/147 (0.7%)	1
Nephropathy	0/144 (0%)	0	1/147 (0.7%)	1
Renal failure acute	6/144 (4.2%)	6	9/147 (6.1%)	9
Renal failure chronic	1/144 (0.7%)	1	0/147 (0%)	0
Renal tubular necrosis	0/144 (0%)	0	1/147 (0.7%)	1
Urinary incontinence	2/144 (1.4%)	2	2/147 (1.4%)	2
Urinary retention	8/144 (5.6%)	8	7/147 (4.8%)	7
Reproductive system and breast disorders
Breast mass	1/144 (0.7%)	1	0/147 (0%)	0
Respiratory, thoracic and mediastinal disorders
Aspiration	1/144 (0.7%)	1	0/147 (0%)	0
Atelectasis	3/144 (2.1%)	3	4/147 (2.7%)	4
Dyspnoea	1/144 (0.7%)	1	1/147 (0.7%)	1
Hypoxia	2/144 (1.4%)	2	1/147 (0.7%)	1
Oropharyngeal pain	1/144 (0.7%)	1	2/147 (1.4%)	2
Pneumonia aspiration	3/144 (2.1%)	3	4/147 (2.7%)	4
Pulmonary hypertension	0/144 (0%)	0	1/147 (0.7%)	1
Pulmonary oedema	3/144 (2.1%)	3	6/147 (4.1%)	6
Respiratory distress	0/144 (0%)	0	2/147 (1.4%)	2
Respiratory failure	1/144 (0.7%)	1	0/147 (0%)	0
Tachypnoea	0/144 (0%)	0	1/147 (0.7%)	1
Wheezing	0/144 (0%)	0	1/147 (0.7%)	1
Skin and subcutaneous tissue disorders
Hyperhidrosis	1/144 (0.7%)	1	0/147 (0%)	0
Pruritus	3/144 (2.1%)	3	0/147 (0%)	0
Rash	2/144 (1.4%)	3	0/147 (0%)	0
Skin ulcer	0/144 (0%)	0	2/147 (1.4%)	2
Vascular disorders
Deep vein thrombosis	1/144 (0.7%)	1	0/147 (0%)	0
Haematoma	1/144 (0.7%)	1	0/147 (0%)	0
Hypertension	2/144 (1.4%)	2	4/147 (2.7%)	4
Hypotension	6/144 (4.2%)	6	6/147 (4.1%)	7
Neurogenic shock	1/144 (0.7%)	1	0/147 (0%)	0
Thrombophlebitis superficial	1/144 (0.7%)	1	0/147 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

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.