Intracerebral Hemorrhage Deferoxamine Trial - iDEF Ttrial

Beth Israel Lahey Health

Status and phase: Completed; Phase 2

Conditions: Intracerebral Hemorrhage

Treatments: Drug: Placebo (for Deferoxamine Mesylate); Drug: Deferoxamine Mesylate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02175225

2012P000005

U01NS074425 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 294 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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294 participants in 2 patient groups, including a placebo group

Deferoxamine Mesylate

Experimental group

Description:

Deferoxamine Mesylate (32 mg/kg/day) given by an intravenous infusion for 3 consecutive days

Treatment:

Drug: Deferoxamine Mesylate

Normal Saline

Placebo Comparator group

Description:

Normal saline (0.9% sodium chloride) given by intravenous infusion for 3 consecutive days

Treatment:

Drug: Placebo (for Deferoxamine Mesylate)