Ignite Creation Date:
2025-12-24 @ 2:16 PM
Ignite Modification Date:
2025-12-28 @ 4:10 AM
Study NCT ID:
NCT01662895
Status:
TERMINATED
Last Update Posted:
2019-06-12
First Post:
2012-07-30
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
High-Dose Deferoxamine in Intracerebral Hemorrhage
Sponsor:
Beth Israel Deaconess Medical Center
Organization:
Study Overview
Official Title:
Futility Study of Deferoxamine in Intracerebral Hemorrhage
Status:
TERMINATED
Status Verified Date:
2019-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
By DSMB on October 18, 2013 due to increased incidence of ARDS. See modified protocol \[NCT02175225
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HI-DEF
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:
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).
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| U01NS074425 | NIH | None | https://reporter.nih.gov/quic… | View |