The Darbepoetin Alfa for Ischemic Surgical Complications (DISC) Dose Finding Trial
Condition: Spinal Ischemia; Stroke; Neuroprotection
MeSH terms: Ischemia
Intervention: Darbepoetin alfa; Standard care
Intervention description: Patients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery
Intervention MeSH terms: Darbepoetin alfa
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Surgical complications; Spinal ischemia; Stroke; Neuroprotection

Summary:

      Numerous neuroprotectants have been effective when given prior to ischemic stroke in animals,
      yet they have all have failed when given after ischemic stroke in humans. A novel approach to
      ischemic neuroprotection is needed. Many patients who undergo cardiac, vascular, and
      neurosurgical procedures develop ischemic central nervous system (CNS) complications. These
      high risk surgeries present a unique opportunity to administer neuroprotectant medication
      prior to the injury, greatly increasing the likelihood that it will have a positive impact on
      outcomes. Patients undergoing descending thoracic aortic (DTA) and thoracoabdominal aortic
      (TAA) surgery have a particularly high rate of both brain and spine ischemia. In addition,
      these surgeries require placement of a lumbar cerebrospinal fluid (CSF) drain, allowing
      access to CSF in order to monitor markers of injury and penetration of medication into the
      CNS. We are performing a pilot dose finding trial of prophylactic darbepoetin alfa, a
      long-acting erythropoiesis medication with putative neuroprotectant properties, in patients
      undergoing DTA and TAA surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are men and women between the ages of 18 - 100 years old (inclusive)

          -  Require descending thoracic or thoracoabdominal aorta surgical repair

          -  Can provide informed consent

        Exclusion Criteria:

          -  Have a traumatic aortic dissection

          -  Have a baseline NIHSS > 1 or modified Rankin Scale > 1

          -  Have a history of stroke or myocardial infarction within the past 30 days

          -  Have a preoperative hemoglobin < 9 or > 14

          -  Have a history of polycythemia vera or essential thrombocytosis

          -  Have a history of hematologic malignancy

          -  Have a history of arterial or venous thrombosis in the past three months

          -  Have uncontrolled hypertension

          -  Have active malignancy requiring treatment

          -  Are receiving hemodialysis

          -  Are currently using recombinant human erythropoietin or darbepoetin alfa, or have an
             expectation to require these medications within 30 days of surgery.

          -  Have a known allergy to recombinant human erythropoietin or darbepoetin alfa

          -  Are pregnant or breast-feeding. Women of childbearing potential must have a negative
             pregnancy test (urine pregnancy test or serum beta-HCG)