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

Primary Purpose

Aneurysmal Subarachnoid Hemorrhage

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Deferoxamine
Placebo
Sponsored by
Aditya S. Pandey, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aneurysmal Subarachnoid Hemorrhage focused on measuring Deferoxamine, Placebo

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • University of MichiganRecruiting
  • Peking University Health Science Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Deferoxamine lower dose

Deferoxamine higher dose

Placebo

Arm Description

Deferoxamine 32 Milligram Per Kilogram (mg/kg)

Deferoxamine 48 mg/kg

normal saline

Outcomes

Primary Outcome Measures

Utility-weighted modified Rankin Scale (UW-mRS) at 6 months
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.

Secondary Outcome Measures

Montreal Cognitive Assessment (MOCA)
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)
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
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)
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
Incidence of delayed cerebral ischemia/vasospasm
This is based on radiographic evidence on computed tomography angiogram and clinical correlation with neurologic exam.

Full Information

First Posted
September 22, 2020
Last Updated
February 17, 2023
Sponsor
Aditya S. Pandey, MD
Collaborators
Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research
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1. Study Identification

Unique Protocol Identification Number
NCT04566991
Brief Title
Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)
Acronym
DISH
Official Title
Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (DISH)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 20, 2022 (Actual)
Primary Completion Date
October 2025 (Anticipated)
Study Completion Date
October 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Aditya S. Pandey, MD
Collaborators
Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aneurysmal Subarachnoid Hemorrhage
Keywords
Deferoxamine, Placebo

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare 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.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deferoxamine lower dose
Arm Type
Experimental
Arm Description
Deferoxamine 32 Milligram Per Kilogram (mg/kg)
Arm Title
Deferoxamine higher dose
Arm Type
Experimental
Arm Description
Deferoxamine 48 mg/kg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
normal saline
Intervention Type
Drug
Intervention Name(s)
Deferoxamine
Other Intervention Name(s)
Desferal
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal Saline
Intervention Description
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.
Primary Outcome Measure Information:
Title
Utility-weighted modified Rankin Scale (UW-mRS) at 6 months
Description
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.
Time Frame
6 months (after hospital discharge)
Secondary Outcome Measure Information:
Title
Montreal Cognitive Assessment (MOCA)
Description
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.
Time Frame
At discharge from hospital (approximately 3-4 weeks)
Title
Montreal Cognitive Assessment (MOCA)
Description
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.
Time Frame
6 months (after hospital discharge)
Title
Percentage of patients requiring permanent cerebrospinal fluid (CSF) diversion due to hydrocephalus at 6 months
Time Frame
6 months
Title
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)
Description
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
Title
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
Title
Incidence of delayed cerebral ischemia/vasospasm
Description
This is based on radiographic evidence on computed tomography angiogram and clinical correlation with neurologic exam.
Time Frame
up to 14 days after aSAH

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sravanthi Koduri
Phone
734-647-7960
Email
skoduri@med.umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Aditya Pandey, MD
Phone
734-615-2763
Email
adityap@umich.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aditya Pandey, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Koduri Sravanthi
Email
skoduri@med.umich.edu
Facility Name
Peking University Health Science Center
City
Beijing
State/Province
Beining
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yining Huang, MD
Phone
+86 10 83572857
Email
ynhuang@bjmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Deferoxamine In the Treatment of Aneurysmal Subarachnoid Hemorrhage (aSAH)

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