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Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH) (DISH)

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ClinicalTrials.gov Identifier: NCT04566991
Recruitment Status : Not yet recruiting
First Posted : September 28, 2020
Last Update Posted : July 21, 2021
Sponsor:
Collaborator:
Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research
Information provided by (Responsible Party):
Aditya S. Pandey, MD, University of Michigan

Tracking Information
First Submitted Date  ICMJE September 22, 2020
First Posted Date  ICMJE September 28, 2020
Last Update Posted Date July 21, 2021
Estimated Study Start Date  ICMJE July 2021
Estimated Primary Completion Date October 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2020)
Utility-weighted modified Rankin Scale (UW-mRS) at 6 months [ Time Frame: 6 months (after hospital discharge) ]
Overall a Bayesian, longitudinal model will be used, this will be adjusted for baseline expected 6 month mRS using the FRESH score. At baseline, the expected 6 month UW-mRS (based on prognostic variables such as age and Hunt Hess) will be entered as the first value for the patient. Therefore, patients with greater severity at baseline, who achieve excellent outcomes will contribute a larger treatment effect. Similarly, patients with greater severity who have disability, but perform better than expected can still contribute useful information.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2020)
  • Montreal Cognitive Assessment (MOCA) [ Time Frame: At discharge from hospital (approximately 3-4 weeks) ]
    Montreal cognitive assessment is a rapid sensitive screening tool for assessment of impaired cognitive function. The main domains of MoCA scale include attention, executive functions, memory, language, attention, naming, orientation, and visual-spatial ability. The total score is 30 points. A score of 25 points or less indicated impaired cognitive function. For patients with less than 12 years of education, one point was added to the total score.
  • Montreal Cognitive Assessment (MOCA) [ Time Frame: 6 months (after hospital discharge) ]
    Montreal cognitive assessment is a rapid sensitive screening tool for assessment of impaired cognitive function. The main domains of MoCA scale include attention, executive functions, memory, language, attention, naming, orientation, and visual-spatial ability. The total score is 30 points. A score of 25 points or less indicated impaired cognitive function. For patients with less than 12 years of education, one point was added to the total score.
  • Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months [ Time Frame: 6 months ]
  • Partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2) ratio (worst value for each parameter for each day of infusion, and 48 hours after end of infusion) [ Time Frame: up to 48 hours after day 3 infusion ]
    Worst value for each parameter for each day of infusion, and 48 hours after end of infusion.
  • To estimate the proportion of non-intubated participants at each dose who experience intubation or initiation of non-invasive positive pressure ventilation during the DFO [ Time Frame: infusion days 1-3 ]
  • Incidence of delayed cerebral ischemia/vasospasm [ Time Frame: up to 14 days after aSAH ]
    This is based on radiographic evidence on computed tomography angiogram and clinical correlation with neurologic exam.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)
Official Title  ICMJE Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (DISH)
Brief Summary

Aneurysmal subarachnoid hemorrhage (aSAH) has a high incidence of mortality and significant morbidity, with mortality exceeding 30% in the first two days.The initial injury is related to increasing intracranial pressure, cerebral edema, and neuronal injuries associated with the release of iron. Iron has been shown to increase the incidence of cerebral edema, ischemia, and formation of hydrocephalus. Deferoxamine mesylate (DFO), a hydrophilic chelator, creates a stable complex with free iron thus preventing the formation of iron related free radicals.

This trial will evaluate the safety and efficacy of clinical deferoxamine for the treatment of aSAH for patients that are admitted to the hospital at the University of Michigan or Peking University Health Science Center. Eligible participants will be enrolled and randomized to 1 of 2 doses of Deferoxamine or placebo (saline). Information regarding the patients will be collected and followed for up to 6 months post discharge.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Masking Description:
All patients and investigators who will be directly involved in the care of these patients or in data analysis will be blinded to randomization status.This trial uses a Bayesian adaptive randomization protocol, where there are three groups that patients will be randomized into: placebo, DFO 32 mg/kg and DFO 48 mg/kg. The first 50 patients will be randomized evenly into each of these groups. The randomization ratio will be adjusted based on the design report after 50 subjects and then every 10 patients.
Primary Purpose: Treatment
Condition  ICMJE Aneurysmal Subarachnoid Hemorrhage
Intervention  ICMJE
  • Drug: Deferoxamine

    There will be 3 doses given to the patients days 1-3. Dose will be given intravenous with a fixed rate of 7.5 milligram per kilogram per hour (mg/kg/hr). The second dose will be given 24 hours after the first dose, and the third dose will be given 48 hours after the initial dose.

    Patients will be randomized to 32 mg/kg or 48 mg/kg of Deferoxamine.

    Other Name: Desferal
  • Drug: Placebo
    There will be 3 doses given to the patients days 1-3. Dose will be given intravenous with a fixed rate of 7.5 mg/kg/hr. The second dose will be given 24 hours after the first dose, and the third dose will be given 48 hours after the initial dose.
    Other Name: Normal Saline
Study Arms  ICMJE
  • Experimental: Deferoxamine lower dose
    Deferoxamine 32 Milligram Per Kilogram (mg/kg)
    Intervention: Drug: Deferoxamine
  • Experimental: Deferoxamine higher dose
    Deferoxamine 48 mg/kg
    Intervention: Drug: Deferoxamine
  • Placebo Comparator: Placebo
    normal saline
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 22, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2025
Estimated Primary Completion Date October 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Aneurysmal SAH confirmed with vascular imaging
  • Aneurysm treated with endovascular or microsurgical intervention
  • Hunt-Hess ≤ 4
  • Modified Fisher Grade I-IV
  • Glasgow Coma Scale (GCS) ≥ 7 following External Ventricular Drain (EVD) placement if indicated
  • First dose of drug can be administered within 24 hours of symptom onset
  • Functional independence prior to SAH, Modified Rankin Scale (mRS) ≤ 1
  • Informed consent obtained by patient or legal authorized representative (LAR)

Exclusion Criteria:

  • Previous hypersensitivity to or treatment with deferoxamine
  • Presence of giant aneurysm (>25 mm in size)
  • Known severe iron deficiency anemia, Hemoglobin (Hgb) g/dl ≤ 7 or transfusion dependent
  • Irreversibly impaired brainstem function
  • Abnormal renal function, Serum Creatinine> 2 mg/dL
  • Pre-existing severe disability, mRS ≥ 2
  • Coagulopathy, including use of anti-platelet or anticoagulant drugs
  • Known severe hearing loss
  • Patients with significant respiratory disease such as chronic obstructive pulmonary disease, pulmonary fibrosis, or on home oxygen (O2)
  • Taking iron supplements containing > 325 mg of ferrous iron
  • Pregnancy
  • Life expectancy less than 90 days due to co-morbidities
  • Concurrent participation in another research protocol for investigation of another experimental therapy, though observational studies are allowed
  • Prior history of hepatic dysfunction
  • Known cytopenia (platelets < 50,000, Absolute neutrophil count < 500)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sravanthi Koduri 734-647-7960 skoduri@med.umich.edu
Contact: Aditya Pandey, MD 734-615-2763 adityap@umich.edu
Listed Location Countries  ICMJE China,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04566991
Other Study ID Numbers  ICMJE HUM00163868
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Aditya S. Pandey, MD, University of Michigan
Study Sponsor  ICMJE Aditya S. Pandey, MD
Collaborators  ICMJE Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research
Investigators  ICMJE
Principal Investigator: Aditya Pandey, MD University of Michigan
PRS Account University of Michigan
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP