Erythropoietin Therapy for Subarachnoid Hemorrhage

NCT00140010 | Completed Phase 2 DMC

• 2 other identifiers: 04/Q0108/872004-001141-15
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

ABSTRACT: Delayed ischemic deficits (DID) and strokes caused by low cerebral blood flow (CBF) are major sources of poor outcome following aneurysmal subarachnoid hemorrhage (SAH). DID are often accompanied by vasospasm and abnormalities in cerebrovascular autoregulation, an important reflex involved in the defense against low CBF. Assessment of vasospasm and impaired autoregulation can be conveniently measured non-invasively by use of transcranial Doppler (TCD) and the transient hyperaemic response test (THRT). Vasospasm and abnormalities in the THRT can predict those patients who are at risk of developing DID. In this study, the investigators wish to explore the neuroprotective and angiogenic effects of systemic erythropoietin (EPO) therapy on vasospasm and autoregulation following SAH, and examine whether any improvements translate into reduced incidences of DID and poor outcome. Eighty patients with SAH will be recruited over one year to receive three doses in the first week of either intravenous epoetin beta 30000 IU or placebo (0.9% saline) 50 ml/30 min as part of a randomized, double-blind, placebo-controlled trial. The investigators propose daily TCD assessment for detecting vasospasm and abnormal autoregulation. Outcome measures will examine the influence of EPO therapy on the incidence, severity, and duration of vasospasm, abnormal autoregulation, and DID. PURPOSE: This study is a randomized, double-blind, placebo-controlled clinical trial investigating the potentially beneficial effects of systemic recombinant human erythropoietin therapy (Epoetin beta, NeoRecormon®, Roche, 30000IU/50 ml/30 min, three times in the first week) on cerebral autoregulation and incidence of delayed ischemic deficits (DID) following aneurysmal subarachnoid haemorrhage (SAH). HYPOTHESIS Systemic recombinant human erythropoietin therapy can be used safely following SAH to ameliorate vasospasm, improve cerebral autoregulation, reduce DID, and facilitate neurological recovery.

Conditions

Aneurysmal Subarachnoid Hemorrhage

Keywords

aneurysm; autoregulation; erythropoietion; stroke; subarachnoid hemorrhage; vasospasm

Outcome Measures

Primary Outcomes (1)

• cerebral vasospasm indices (incidence, onset, severity) on transcranial Doppler

  14 days following aneurysmal subarachnoid hemorrhage

Secondary Outcomes (2)

• delayed ischemic neurological deficits

  14 days following aneurysmal subarachnoid haemorrhage

• disability measured with modified Rankin Scale, Glasgow Outcome Scale, National Institute of Stroke Scale

  6 months following aneurysmal subarachnoid haemorrhage

Study Arms (1)

A

EXPERIMENTAL

30,000 units of erythropoietin beta in one vial; 3 vials as one set per patient

Drug: erythropoietin beta

Interventions

erythropoietin beta DRUG

30,000 units in 6 mL of 0.9% saline IV for 15 minutes every other day for 3 doses within 72 hours after aneurysmal subarachnoid hemorrhage

Also known as: erythropoietin, epoetin

A

Eligibility Criteria

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

You may qualify if:

• Adult patients (\>= 18 years)
• Aneurysmal subarachnoid hemorrhage

You may not qualify if:

• Uncontrolled systemic hypertension (systolic blood pressure \> 220 mmHg)
• Erythrocytosis vera
• Concurrent erythropoietin therapy
• Negative angiography
• Subarachnoid hemorrhage more than 7 days

Sponsors & Collaborators

• University of Cambridge: lead
• Hoffmann-La Roche: collaborator
• Roche Foundation of Anemia Research (RoFAR, Switzerland): collaborator

Study Sites (1)

Department of Neurosurgery, Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

Location

Related Publications (1)

• 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 Jul;111(1):171-80. doi: 10.3171/2009.3.JNS081332.

  PMID: 19344224 RESULT

MeSH Terms

Conditions

Subarachnoid Hemorrhage; Aneurysm; Stroke

Interventions

Erythropoietin

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Peter J Kirkpatrick, FRCS(SN)

  University of Cambridge

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 29, 2005
• First Posted: August 31, 2005
• Study Start: April 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: March 1, 2007
• Last Updated: May 20, 2009

Record last verified: 2009-05

Locations

GB (1)