The Darbepoetin Alfa for Ischemic Surgical Complications (DISC) Dose Finding Trial
Condition: Spinal Ischemia; Stroke; Neuroprotection
MeSH terms: Ischemia
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      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 performed 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. This dose finding trial was stopped early after 9 patients were enrolled
      at the request of the FDA after an unrelated trial of erythropoietin in acute stroke
      performed in Germany was negative and showed possible harm in those patients who received
      intravenous tissue plasminogen activaor (tPA). We then enrolled 9 additional patients who did
      not receive any intervention in order to compare them to the patients who received
      darbepoetin.
    

Intervention name(s): Darbepoetin alfa; Standard care
Intervention type(s): Drug; Other
Intervention description(s): Patients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery
Other intervention name(s): Aranesp
Intervention MeSH terms: Darbepoetin alfa
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Surgical complications; Spinal ischemia; Stroke; Neuroprotection