Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE2
42 participants
INTERVENTIONAL
2013-03-18
2018-05-10
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Deferoxamine and Xingnaojing Injection Treatment in Intracerebral Hemorrhage
NCT02367248
Study of Antithrombotic Treatment After IntraCerebral Haemorrhage
NCT03186729
Effects of Dexmedetomidine on Inflammatory Cytokines in Patients With Aneurysmal Subarachnoid Hemorrhage
NCT01565590
Dexamethasone Versus Burr Hole Craniostomy for Symptomatic Chronic Subdural Hematoma
NCT02111785
Monitoring of Delayed Ischemia After Subarachnoid Hemorrhage
NCT01406457
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
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).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
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.
Normal Saline
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.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
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.
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 Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
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
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.
18 Years
80 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
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
UNKNOWN
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
Beth Israel Deaconess Medical Center
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Magdy Selim
Professor of Neurology
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Magdy Selim, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Beth Israel Deaconess Medical Center/Harvard Medical School
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
St. Joseph's Hospital
Phoenix, Arizona, United States
Stanford University Hospital
Palo Alto, California, United States
San Francisco General Hospital
San Francisco, California, United States
Hartford Hospital
Hartford, Connecticut, United States
Yale New Haven Hospital
New Haven, Connecticut, United States
The University of Florida College of Medicine
Jacksonville, Florida, United States
University of Iowa Hospital
Iowa City, Iowa, United States
University of Maryland Medical Center
Baltimore, Maryland, United States
Johns Hopkins Hospital
Baltimore, Maryland, United States
Tufts Medical Center
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
University of North Carolina Medical Center
Chapel Hill, North Carolina, United States
Duke University Hospital
Durham, North Carolina, United States
The Cleveland Clinic Foundation
Cleveland, Ohio, United States
The Ohio State University Medical Center
Columbus, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, United States
Rhode Island Hospital
Providence, Rhode Island, United States
Medical University of South Carolina
Charleston, South Carolina, United States
The University of Texas Health Science Center
Houston, Texas, United States
University of Virginia Health System
Charlottesville, Virginia, United States
Harborview Medical Center
Seattle, Washington, United States
Foothills Medical Center
Calgary, Alberta, Canada
Mackenzie Health Sciences Centre
Edmonton, Alberta, Canada
Halifax Infirmary
Halifax, Nova Scotia, Canada
Hôpital de l'Enfant-Jésus - CHU de Québec
Québec, , Canada
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
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.
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.
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.
Roh DJ, Poyraz FC, Mao E, Shen Q, Kansara V, Cottarelli A, Song S, Nemkov T, Kumar A, Hudson KE, Ghoshal S, Park S, Agarwal S, Connolly ES, Claassen J, Kreuziger LB, Hod E, Yeatts S, Foster LD, Selim M. Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome. J Am Heart Assoc. 2024 Jul 16;13(14):e035524. doi: 10.1161/JAHA.124.035524. Epub 2024 Jul 9.
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.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2012P-000005
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.