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.
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.
Brief Title
Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Intracerebral Hemorrhage
Eligibility Criteria
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
* 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
Inclusion Criteria
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.
* 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.
Gender
All
Gender Based
false
Keywords
Brain hemorrhage
Cerebral hemorrhage
Bleeding in the brain
Deferoxamine
iDEF trial
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
80 Years
Minimum Age
18 Years
NCT Id
NCT02175225
Org Class
Other
Org Full Name
Beth Israel Deaconess Medical Center
Org Study Id
2012P000005
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Study of Deferoxamine Mesylate in Intracerebral Hemorrhage
Primary Outcomes
Outcome 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.
Outcome Measure
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 90 Days
Outcome Time Frame
90 days
Outcome Description
Number of subjects experiencing Serious adverse events at any time from randomization through day 90
Outcome Measure
Number of Subjects Experiencing Serious Adverse Events
Outcome Time Frame
90 days
Outcome Description
Number of Subjects Experiencing Serious Adverse Events within 7 days of randomization
Outcome Measure
Number of Subjects With Serious Adverse Events Within 7 Days
Outcome Time Frame
7 days
Secondary Ids
Secondary Id
U01NS074425
Secondary Outcomes
Outcome 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.
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.
Outcome Time Frame
90 days
Outcome Measure
Proportion of Patients With mRS Score 0-3 at 90 Days
Outcome 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.
Outcome Time Frame
180 days
Outcome Measure
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-2 at 180 Days
Outcome 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.
Outcome Time Frame
180 days
Outcome Measure
Proportion of Patients With Modified Rankin Scale (mRS) Score 0-3 at 180 Days
Outcome 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.
Outcome Time Frame
90 days
Outcome Measure
Proportion of Subjects With Good Outcome (mRS 0-2) in the Early vs. Delayed Treatment Time Windows
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
80
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Rishi Malhotra
Investigator Email
rmalhotr@montefiore.org
Investigator Phone