Contact information
Type
Scientific
Primary contact
Mr Peter John Kirkpatrick
ORCID ID
Contact details
Box 167
Department of Neurosurgery
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 2QQ
United Kingdom
+44 01223 217214
pjk21@medschl.cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N0544163605
Study information
Scientific title
Acronym
Study hypothesis
Can a short-term systemic treatment with erythropoietin, a red blood cell producing human hormone, prevent strokes caused by bleeding on the brain (subarachnoid haemorrhage)?
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Cardiovascular: Stroke
Intervention
Randomisation procedure:
Following informed consent patients will be randomised to receive either intravenous r-HuEPO 30,000IU or placebo (0.9% saline) 50ml/30min, three times in the first week after SAH (total dose 100,000IU). The number in each group will be 40. For blinding, the Pharmacy Manufacture Unit (PMU) will prepare and number identical vials containing either saline (0.9% NaCl) or r-HuEPO reconstituted in saline. The vials will be randomly assigned to patients upon enrollment with the contents of each vial known only by the PMU. Trial medication will be started as soon as possible within 72 hours of the ictus. As approximately 70% of aneurysms will be treated with open clipping, and the remainder with endovascular coils, we do not consider the method of treatment to represent a contaminating factor, but it will be included in the final analysis. Location, size, and morphology of the culprit aneurysm are not believed to affect outcome in our institution.
Following randomisation and start of trial therapy the clinical management of each patient will be as routine. Arterial blood pressure will be continuously monitored (Finapress, or via radial arterial line).
Safety:
The full blood cell count, reticulocyte count, blood viscosity, coagulation profile, serum biochemistry, serum iron levels, and C-reactive protein (CRP) at the time of admission will be checked as baseline data and repeated alternate days for the duration of the trial drug administration. Although r-HuEPO has effects of erythropoiesis and thrombopoiesis, associated deterioration or adverse events have not been observed in short-term treatment However, in the face of any abnormalities the trial drug will be stopped and the safety committee informed. A safety committee (chaired by Dr Ken Smith, Consultant nephrologist) will review the safety data at monthly intervals or, if concerns arise, on a patient-by-patient basis.
Trial patients will be examined daily with TCD (DWL, Germany) using a 2-MHz probe mounted on a purposed head frame for two weeks since SAH ictus. The systolic, diastolic, and mean FV will be recorded (trans-temporal) by a single user (MT). Vasospasm will be defined as mean FV > 120 cm/sec and Lindegaard ratio >3. The regression index (Mx) between mean FV and spontaneous changes in ABP will be calculated. Two carotid compressions lasting 5 seconds will be performed. The criteria for an acceptable THRT includes a sudden decrease in middle cerebral artery FV at the onset of compression, a stable TCD signal during compression, and a minimum of 30% decrease in FV with no blood pressure instability. The THRT ratio (THRR) is calculated using the formula: THRR = FVs (hyperaemia) / FVs(baseline), where FVs denotes systolic FV. THRR is classified as normal (=l.10) or impaired (<1.10), and will be repeated 2 minutes later. The average value of the two tests will be recorded. Quality issues concerning the THRT response have been extensively evaluated in this laboratory.
Intervention type
Drug
Phase
Phase II
Drug names
erythropoietin
Primary outcome measures
Vasospasm and abnormal cerebral autoregulation shown on transcranial Doppler.
Trial patients will be examined daily with TCD (DWL, Germany) using a 2-MHz probe mounted on a purposed head frame for two weeks since SAH ictus. The systolic, diastolic, and mean FV will be recorded (trans-temporal) by a single user (MT). Vasospasm will be defined as mean FV > 120 cm/sec and Lindegaard ratio >3. The regression index (Mx) between mean FV and spontaneous changes in ABP will be calculated. Two carotid compressions lasting 5 seconds will be performed. The criteria for an acceptable THRT includes a sudden decrease in middle cerebral artery FV at the onset of compression, a stable TCD signal during compression, and a minimum of 30% decrease in FV with no blood pressure instability. The THRT ratio (THRR) is calculated using the formula: THRR = FVs (hyperaemia) / FVs(baseline), where FVs denotes systolic FV. THRR is classified as normal (=l.10) or impaired (<1.10), and will be repeated 2 minutes later. The average value of the two tests will be recorded. Quality issues concerning the THRT response have been extensively evaluated in this laboratory.
Secondary outcome measures
Development of DID. The clinical progress of each patient will be monitored daily. The development of a focal neurological deficit and/or a drop in the GCS by 2 points or more will be the criteria adopted to define an episode of DID [Pickard 1989]. Clinical and radiological outcomes will be assessed at the time of discharge. Durations of hospitalisation and NCCU stay will be observed.
Overall trial start date
01/01/2005
Overall trial end date
30/04/2006
Reason abandoned
Eligibility
Participant inclusion criteria
Patients >= 18 years old with suspected aneurysmal SAH admitted to the Addenbrooke's Neurosurgical Department will be approached.
Participant type
Patient
Age group
Adult
Gender
Not Specified
Target number of participants
80
Participant exclusion criteria
Uncontrolled systemic hypertension (systolic blood pressure >220 mmHg), time after SAH ictus has been 7 days, traumatic or angiography-negative SAH. Patients over 65 years will have carotid duplex examinations to exclude those with significant carotid atheroma.
Recruitment start date
01/01/2005
Recruitment end date
30/04/2006
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Box 167, Department of Neurosurgery, Addenbrooke's Hospital
Cambridge
CB2 2QQ
United Kingdom
Sponsor information
Organisation
Record Provided by the NHSTCT Register - 2006 Update - Department of Health
Sponsor details
The Department of Health
Richmond House
79 Whitehall
London
SW1A 2NL
United Kingdom
+44 (0)20 7307 2622
dhmail@doh.gsi.org.uk
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Cambridge Consortium - Addenbrooke's (UK) NHS R&D Support Funding
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19344224
Publication citations
-
Results
Tseng MY, Hutchinson PJ, Richards HK, Czosnyka M, Pickard JD, Erber WN, Brown S, Kirkpatrick PJ, Acute systemic erythropoietin therapy to reduce delayed ischemic deficits following aneurysmal subarachnoid hemorrhage: a Phase II randomized, double-blind, placebo-controlled trial. Clinical article., J. Neurosurg., 2009, 111, 1, 171-180, doi: 10.3171/2009.3.JNS081332.