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

NCT00647998 | Completed Phase 2 Results

• 1 other identifier: DISC-001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Ischemia; Stroke; Neuroprotection

Keywords

Surgical complications; Spinal ischemia; Stroke; Neuroprotection

Outcome Measures

Primary Outcomes (1)

• 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

  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.

  Discharge from the hospital

Secondary Outcomes (2)

• CSF S100beta

  48 hours

• Hemoglobin

  24 hours post-surgery

Study Arms (2)

Darbepoetin

EXPERIMENTAL

Patients received 1mg/kg IV Darbepoetin immediately prior to surgery

Drug: Darbepoetin alfa; Other: Standard care

Standard care

PLACEBO COMPARATOR

No Darbepoetin

Other: Standard care

Interventions

Darbepoetin alfa DRUG

Patients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery

Also known as: Aranesp

Darbepoetin

Standard care OTHER

Darbepoetin; Standard care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Messe SR, McGarvey ML, Bavaria JE, Pochettino A, Szeto WY, Cheung AT, Leitner E, Miller SW, Kasner SE. A pilot study of darbepoetin alfa for prophylactic neuroprotection in aortic surgery. Neurocrit Care. 2013 Feb;18(1):75-80. doi: 10.1007/s12028-012-9710-4.

  PMID: 22528284 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Darbepoetin alfa; Standard of Care

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Erythropoietin; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Proteins; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Steven Messe, MD
• Organization: Hospital of the University of Pennsylvania

messe@mail.med.upenn.edu

2156623363

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of neurology

Study Record Dates

• First Submitted: March 27, 2008
• First Posted: April 1, 2008
• Study Start: January 1, 2008
• Primary Completion: July 1, 2010
• Study Completion: October 1, 2010
• Last Updated: June 5, 2017
• Results First Posted: January 2, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)