Spinal IschemiaPhase 2DISCNCT00647998
The Darbepoetin Alfa for Ischemic Surgical Complications (DISC) Dose Finding Trial
A Phase 2 study testing Darbepoetin alfa in people with Spinal Ischemia and Stroke, run by University of Pennsylvania at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Spinal Ischemia, Stroke, Neuroprotection
- What is being tested?
- Darbepoetin alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Phase 2 Dose Finding Trial of Prophylactic Darbepoetin Alfa to Improve Outcomes From Ischemic Complications of Surgery
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.
Read the 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
- Being tested
- Darbepoetin alfa, Standard care
- Keywords
- Surgical complications, Spinal ischemia, Stroke, Neuroprotection
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Darbepoetin alfaDrug
Also called Aranesp
Patients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery
Standard careOther
| Study group | Role | What they receive |
|---|---|---|
| Darbepoetin | Experimental | Patients received 1mg/kg IV Darbepoetin immediately prior to surgery Receives: Drug: Darbepoetin alfa; Other: Standard care |
| Standard care | Placebo comparator | No Darbepoetin Receives: Other: Standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Discharge from the hospital
Secondary outcomes (2)
CSF S100beta
Cerebrospinal fluid S100beta level
Measured: 48 hours
Hemoglobin
Measured: 24 hours post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2008 (estimated)
- Study startJan 2008
- Primary completionJul 2010
- Study completionOct 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Spinal IschemiaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Steven Messe, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00647998
- Sponsor's protocol ID
- DISC-001
- Acronym
- DISC
- Status last verified
- May 2017
- First submitted
- 27 Mar 2008
- Last updated
- 5 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 22528284
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Dose Finding Trial of Prophylactic Darbepoetin Alfa to Improve Outcomes From Ischemic Complications of Surgery
- ClinicalTrials.gov ID
- NCT00647998
- Acronym / sponsor ID
- DISC / DISC-001
- Conditions
- Spinal Ischemia, Stroke, Neuroprotection
- Keywords
- Surgical complications, Spinal ischemia, Stroke, Neuroprotection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Jul 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 1 Apr 2008 (estimated)
- Results
- Posted 2 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Darbepoetin | Experimental | Drug: Darbepoetin alfa, Other: Standard carePatients received 1mg/kg IV Darbepoetin immediately prior to surgery |
| Standard care | Placebo comparator | Other: Standard careNo Darbepoetin |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Darbepoetin alfaAlso: AranespPatients will receive one IV injection of Darbepoetin alfa at doses ranging from 1mcg/kg to 6.5 mcg/kg prior to surgery | Drug | Darbepoetin |
| Standard care | Other | Darbepoetin, Standard care |
Primary outcome
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.
2 secondary outcomes
CSF S100beta
Time frame: 48 hours
Hemoglobin
Time frame: 24 hours post-surgery
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22528284Messe 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Darbepoetin alfa in people with Spinal Ischemia and Stroke, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00647998, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2017.