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

NCT ID: NCT00647998

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2010-10-31

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.

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.

Conditions

Spinal Ischemia; Stroke; Neuroprotection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Darbepoetin

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

Group Type: EXPERIMENTAL

Darbepoetin alfa

Intervention Type: DRUG

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

Standard care

Intervention Type: OTHER

Standard care

No Darbepoetin

Group Type: PLACEBO_COMPARATOR

Standard care

Intervention Type: OTHER

Interventions

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

Intervention Type: DRUG

Standard care

Intervention Type: OTHER

Other Intervention Names

Aranesp

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Steven Messe

Associate professor of neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 22528284 (View on PubMed)

Other Identifiers

DISC-001

Identifier Type: -

Identifier Source: org_study_id