Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial
Condition: Intracerebral Hemorrhage
MeSH terms: Cerebral Hemorrhage; Hemorrhage
Intervention: Deferoxamine Mesylate; Placebo (for Deferoxamine Mesylate)
Intervention MeSH terms: Deferoxamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 294.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Brain hemorrhage; Cerebral hemorrhage; Bleeding in the brain; Deferoxamine; iDEF trial

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.
    

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