High-Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01662895|
Recruitment Status : Terminated (By DSMB on October 18, 2013 due to increased incidence of ARDS. See modified protocol [NCT02175225)
First Posted : August 13, 2012
Results First Posted : May 30, 2019
Last Update Posted : June 12, 2019
|Condition or disease||Intervention/treatment||Phase|
|Intracerebral Hemorrhage||Drug: Deferoxamine Drug: Normal saline||Phase 2|
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:
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Futility Study of Deferoxamine in Intracerebral Hemorrhage|
|Actual Study Start Date :||March 18, 2013|
|Actual Primary Completion Date :||January 15, 2014|
|Actual Study Completion Date :||May 10, 2018|
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.
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 Name: 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 Name: 0.90% Sodium Chloride Solution
- Number of Subjects With Modified Rankin Scale (mRS) Score 0-2 [ Time Frame: 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).
- Number of Subjects With mRS Score 0-3 [ Time Frame: 90 days ]The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days
- Number of Subjects With Allergic/Anaphylactic Reaction [ Time Frame: within 7 days or discharge ]
- Number of Patients With Hypotension [ Time Frame: within 7 days or discharge ]
- Number of Patients With New Visual or Auditory Changes [ Time Frame: within 7 days or discharge ]
- Number of Patients With Serious Adverse Events [ Time Frame: 90 days ]
- Number of Patients Who Died During the 90-day Study Period [ Time Frame: 90 days ]Mortality at any time from randomization through day-90
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01662895
|Principal Investigator:||Magdy Selim, MD, PhD||Beth Israel Deaconess Medical Center/Harvard Medical School|