The Tilburg Vasospasm Study

Prevention of Secondary Ischemia After Aneurysmal Subarachnoid Hemorrhage With Cerebrospinal Fluid Drainage. A Randomized Controlled Trial

In a prospective randomized controlled trial, the investigators aim to assess whether external lumbar drainage (ELD) of CSF is safe and reduces delayed cerebral ischemia and its sequelae in patients with an aneurysmal subarachnoid hemorrhage.

Study Overview

• Status: Terminated
• Conditions: Brain Ischemia; Intracranial Vasospasm
• Intervention / Treatment: Procedure: external lumbar drainage (ELD) of cerebrospinal fluid

Detailed Description

Delayed cerebral ischemia (DCI) is a frequent complication after an aneurysmal subarachnoid hemorrhage (SAH). Its pathophysiological mechanism remains unclear but a role for cerebral vasospasm and the presence of blood in the arachnoid space is likely. A wash out of blood and blood breakdown products in the cerebrospinal fluid (CSF) could reduce the incidence of vasospasm and DCI.

We aim to assess whether external lumbar drainage (ELD) of CSF is safe and reduces secondary ischemia and its sequelae.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Brabant
    • Tilburg, Brabant, Netherlands, 5022 GC
      • St Elisabeth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• spontaneous subarachnoid hemorrhage (SAH) with aneurysmal pattern graded as a Fisher grade III or higher on cerebral CT-scan.
• CSF drainage by external lumbar catheter can start within 96 hours after the initial SAH
• the drainage can start prior to the treatment of the ruptured aneurysm
• informed consent is signed by the patient or his representative

Exclusion Criteria:

• spontaneous SAH with aneurysmal pattern graded as a Fisher grade I or II on CT and perimesencephalic hemorrhages
• traumatic SAH
• symptomatic hydrocephalus on admission necessitating drainage (EVD or ELD)
• the presence of a large intraventricular bloodclot in the third or fourth ventricle on CT
• the presence of a mass lesion with significant cerebral midline shift
• all patients whose neurological condition is too poor to allow clinical recognition of signs and symptoms of cerebral vasospasm. This includes all patients with a Hunt and Hess Grade V who failed to improve after initial resuscitation
• no informed consent
• mycotic aneurysms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: external lumbar drainage; Within 96 hours of initial subarachnoid hemorrhage, patients were randomized for external lumbar drainage (ELD)of cerebrospinal fluid during a maximum of 7 days or standard treatment of subarachnoid hemorrhage without ELD	Procedure: external lumbar drainage (ELD) of cerebrospinal fluid; Patients were randomized for external lumbar drainage of cerebrospinal fluid or standard treatment of a subarachnoid hemorrhage alone. External drainage was started within 96 hours of initial subarachnoid hemorrhage during 7 days at a maximum of 5-10 ml/hour.
No Intervention: No intervention; In this arm the patients received standard treatment following protocol for patients with subarachnoid hemorrhage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical signs of delayed cerebral ischemia	DCI was diagnosed when all of the following criteria were met: (1) the onset of new neurological deficits such as confusion, disorientation, drowsiness, or focal deficit during post-hemorrhage days (4 to 14); (2) negative findings on CT obtained to rule out other causes of neurological deterioration such as hemorrhage, cerebral edema, or hydrocephalus. (3) No other identifiable cause of neurological deterioration such as hyponatriemia, hypoxia, drug toxicity, infection, or seizures.	Patients will be followed for the duration of admission, an expected average of 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dichotomized Glasgow outcome score (GOS)	Glasgow outcome scale was measured at discharge	at discharge, an expected average of 3 weeks after initial bleeding
new ischemic lesions on cerebral CT scan		at 3 months after initial bleeding
length of stay in intensive care unit	The length of stay in the intensive care unit will be measured.	Patients will be followed from initial admission until discharge, an expected average of 3 weeks
rebleeding rate of unsecured aneurysms and complications of external lumbar drainage	Evaluation of rebleeding rate of unsecured cerebral aneurysms during external lumbar drainage (ELD) of cerebrospinal fluid and evaluation of (other) complications of ELD such as (local)infection, discomfort/pain.	Patients willl be followed from initial bleeding until treatment of aneurysm, an expected average of 3 days
dichotomized Glasgow outcome score (GOS		at 3 months after initial bleeding
clinical signs of delayed cerebral ischemia	As stated in first primary outcome measure 'clinical signs of cerebral ischemia' during admission.	At 3 months after initial bleeding

Collaborators and Investigators

• Sponsor: Elisabeth-TweeSteden Ziekenhuis
• Investigators: Principal Investigator: Paul Depauw, MD, Elisabeth-TweeSteden Ziekenhuis

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: January 10, 2011
• First Submitted That Met QC Criteria: August 1, 2011
• First Posted (Estimate): August 2, 2011

Study Record Updates

• Last Update Posted (Estimate): August 2, 2011
• Last Update Submitted That Met QC Criteria: August 1, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: Subarachnoid hemorrhage; vasospasm; delayed cerebral ischemia; external lumbar drainage
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hemorrhage; Intracranial Hemorrhages; Brain Ischemia; Ischemia; Subarachnoid Hemorrhage; Vasospasm, Intracranial
• Other Study ID Numbers: 15378