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The Darbepoetin Alfa for Ischemic Surgical Complications (DISC) Dose Finding Trial (DISC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven Messe, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00647998
First received: March 27, 2008
Last updated: May 1, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Spinal Ischemia Stroke Neuroprotection Drug: Darbepoetin alfa Other: Standard care Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Dose Finding Trial of Prophylactic Darbepoetin Alfa to Improve Outcomes From Ischemic Complications of Surgery

Resource links provided by NLM:


Further study details as provided by Steven Messe, University of Pennsylvania:

Primary Outcome Measures:
  • Death or Neurologic Disability, Defined as an National Institutes of Health Stroke Scale (NIHSS)>4 or American Spinal Injury Association (ASIA) Lower Extermity Motor Score <25 [ Time Frame: Discharge from the hospital ]
    The NIHSS is a validated quasi-ordinal measure of stroke severity. An NIHSS >4 is generally considered moderate or severe. The ASIA Lower Extremity Motor Score is a cumulative total of assessments of strength in 5 muscles in each leg, using the Medical Research Council 0-5 stroke score. ASIA score < 25 is associated with impaired ambulation.


Secondary Outcome Measures:
  • CSF S100beta [ Time Frame: 48 hours ]
    Cerebrospinal fluid S100beta level

  • Hemoglobin [ Time Frame: 24 hours post-surgery ]

Enrollment: 18
Study Start Date: January 2008
Study Completion Date: October 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Darbepoetin
Patients received 1mg/kg IV Darbepoetin immediately prior to surgery
Drug: Darbepoetin alfa
Patients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery
Other Name: Aranesp
Other: Standard care
Placebo Comparator: Standard care
No Darbepoetin
Other: Standard care

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.
  Eligibility

Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00647998

Locations
United States, Pennsylvania
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Steven Messe, Associate professor of neurology, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00647998     History of Changes
Other Study ID Numbers: DISC-001
Study First Received: March 27, 2008
Results First Received: November 3, 2016
Last Updated: May 1, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Steven Messe, University of Pennsylvania:
Surgical complications
Spinal ischemia
Stroke
Neuroprotection

Additional relevant MeSH terms:
Ischemia
Pathologic Processes
Darbepoetin alfa
Hematinics

ClinicalTrials.gov processed this record on September 20, 2017