High-Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF)
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ClinicalTrials.gov Identifier: NCT01662895 |
Recruitment Status
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Suspended
(By DSMB due to increased incidence of ARDS. See modified protocol [NCT02175225)
First Posted
: August 13, 2012
Last Update Posted
: January 9, 2018
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Tracking Information | ||||
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First Submitted Date ICMJE | July 30, 2012 | |||
First Posted Date ICMJE | August 13, 2012 | |||
Last Update Posted Date | January 9, 2018 | |||
Actual Study Start Date ICMJE | March 2013 | |||
Estimated Primary Completion Date | December 2018 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Proportion of patients with Modified Rankin Scale (mRS) Score 0-2 [ Time Frame: 3 months ] The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional out-come as mRS 0-2 at 90 days.
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | Complete list of historical versions of study NCT01662895 on ClinicalTrials.gov Archive Site | |||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Outcome Measures ICMJE | Not Provided | |||
Original Other Outcome Measures ICMJE | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | High-Dose Deferoxamine in Intracerebral Hemorrhage | |||
Official Title ICMJE | Futility Study of Deferoxamine in Intracerebral Hemorrhage | |||
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. | |||
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:
Secondary and exploratory objectives include:
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. The HI-DEF study also provides an opportunity to "bank" blood samples from the participants for future innovative research in ICH. We, therefore, plan to collect additional blood samples from the participants in HI-DEF at baseline, before the start of the study drug infusion, and after completion of the last infusion to be stored and analyzed in the future. The exact questions to be asked and tests to be done in the future are not fully identified at this stage. If the efforts to develop deferoxamine as a therapy for ICH are successful, future pharmacogenetic studies may help to define other therapeutic targets and responders vs. non-responders to deferoxamine therapy. We tentatively plan to investigate the relationship between polymorphisms from a panel of genes encoding iron-handling proteins (which includes genes involved in both intra- and extra-cellular iron metabolism, such as ceruloplasmin, haptoglobin, hemopexin, transferrin receptor, ferritin heavy- and light-chain, and heme-oxygenase 1 and 2 genes) and peri-hematoma edema; outcome; and response to deferoxamine therapy. |
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Study Type ICMJE | Interventional | |||
Study Phase | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Condition ICMJE | Intracerebral Hemorrhage | |||
Intervention ICMJE |
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Study Arms |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Suspended | |||
Estimated Enrollment ICMJE |
324 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Estimated Study Completion Date | December 2018 | |||
Estimated Primary Completion Date | December 2018 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender |
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Ages | 18 Years to 80 Years (Adult, Senior) | |||
Accepts Healthy Volunteers | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Canada, United States | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01662895 | |||
Other Study ID Numbers ICMJE | 2012P-000005 U01NS074425 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement | Not Provided | |||
Responsible Party | Magdy Selim, Beth Israel Deaconess Medical Center | |||
Study Sponsor ICMJE | Beth Israel Deaconess Medical Center | |||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | Beth Israel Deaconess Medical Center | |||
Verification Date | January 2018 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |