Clinical trial NCT00842049: Lumbar Drainage in Subarachnoid Haemorrhage
Official title: Lumbar Drainage of Cerebrospinal Fluid in Aneurysmal Subarachnoid Haemorrhage: A Prospective Randomised Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Subarachnoid Hemorrhage
Keywords: Subarachnoid haemorrhage
Aneurysm
Cerebrospinal fluid drainage
Lead sponsor: The Leeds Teaching Hospitals NHS Trust
Sponsor class: OTHER
First posted: 2009-02-12
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Subarachnoid haemorrhage affects approximately 8000 people per year in the UK. The average age of a patient with subarachnoid haemorrhage is 50 years, although it is often seen in younger people (25-45 years). Despite modern medicine, the death and disability rate remains high both from the initial bleed and from the associated complications such as vasospasm. This is characterised by neurological impairment seen following the bleed. Despite modern treatment this is still associated with a poor outcome. This has significant implications due to the long term intensive neuro-rehabilitation these patients will require.

A recent study has shown that placing a small drain in the lower back following a subarachnoid haemorrhage may reduce the chance of vasospasm occurring and result in a better outcome. This trial was not optimally performed and so a trial is needed to look at this in more detail. The investigators have set up such a trial in our neurosurgical unit. If the investigators confirm that there is an improvement in patient outcome, it will change our practice in the future.

Detailed description: All patients who present to our department with proven aneurysmal SAH and fit the inclusion criteria (see below) will be approached for inclusion into the trial. Written informed consent will be sought prior to recruitment into the study. Written assent from the patient's relatives will be sought in those cases where neurological impairment prevents written informed consent being obtained from the patient. The patient will subsequently be randomised into the control arm or the study arm of the trial. The control arm consists of normal therapeutic intervention, including external ventricular drainage if required for hydrocephalus. Those randomised to the therapeutic arm will have a lumbar drain inserted and set to drain CSF at 5 ml/hour. This will continue until CSF is no longer blood stained or until day 10 following insertion.

Primary outcome measures:

1. Incidence of delayed ischaemic neurological deficit. This is defined as new neurological deficit and/or impairment of consciousness without other identifiable cause at least three days post haemorrhage.

New impairment of consciousness is defined as a drop in the Glasgow Coma Score of 1 motor point or 2 verbal/eye opening points.

Secondary outcome measures:

1. Modified Rankin Score at day 10 post ictus and at 6 months.
2. Severity of delayed neurological deficit and the development of a complete infarct.
3. Incidence of cerebrospinal fluid infection secondary to lumbar drainage

Special note:

If a patient has presented greater than three days following the initial bleed, any neurological deficit present may be a delayed neurological deficit and thus must be excluded from the trial. Should the lumbar drain fall out prematurely the patient will be asked whether they wish to continue in the study and, if so, the lumbar drain will be reinserted and management will continue as before. Patients showing signs of lumbar drain infection will have the drain removed, a sample of CSF and the drain tip sent to the microbiology laboratory and appropriate antibiotic therapy instituted.

The neurosurgical unit at Leeds General Infirmary treated 313 patients with acute subarachnoid haemorrhage in the three years 1997-2000. Of these 243 patients would have been suitable for this study on the basis of their admission clinical status. The power calculation was derived from the estimate that 40% of patients treated with standard therapy will develop clinical vasospasm. If the retrospective study showed a minimum of 20% improvement in its outcome variables then we expect to see the same improvement. For an 85% power this requires 105 patients in each arm. We expect this to take 3.5 years based on the number of eligible patients that present to our unit with a 60-70% recruitment rate (approximately 30 patients per year per arm).

Eligibility criteria: Inclusion Criteria:

1. Aneurysmal subarachnoid haemorrhage.
2. Recruitment prior to day three post-haemorrhage.
3. Written informed consent or relative assent given.
4. WFNS grade 1-3.
5. Fisher grade 2, 3 and 4 (without space occupying haematoma) on initial CT scan.
6. No intraventricular haemorrhage, space occupying haematoma or other contra-indication to lumbar puncture.

Exclusion Criteria:

1. Non-aneurysmal subarachnoid haemorrhage.
2. Delayed presentation / recruitment (after day three post-haemorrhage)
3. Written informed consent or relative assent denied or unobtainable.
4. WFNS grade 4 or 5.
5. Fisher grade 1 on initial CT scan.
6. Intraventricular haematoma obstructing ventricular outflow.
7. Intracranial haematoma with mass effect.
8. Bleeding diathesis.

Primary outcomes:
measure: Incidence of delayed ischaemic neurological deficit
timeFrame: Within 21 days of haemorrhagic ictus
Secondary outcomes:
measure: Modified Rankin Score
timeFrame: 10 days and 6 months following haemorrhagic ictus
measure: Incidence of cerebrospinal fluid shunting
timeFrame: Within 12 months of haemorrhagic ictus
measure: Incidence of completed infarct secondary to delayed ischaemic neurological deficit
timeFrame: Within 21 days of ictus
measure: Incidence of cerebrospinal fluid infection secondary to lumbar drainage
timeFrame: Within 8 weeks of removal of lumbar drain
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
state: West Yorkshire
Study officials:
affiliation: Leeds Teaching Hospital NHS Trust
name: Yahia Al-Tamimi, MCChB(Hons)
role: PRINCIPAL_INVESTIGATOR
affiliation: Leeds Teaching Hospital NHS Trust
name: Stuart Ross, FRCS(SN)
role: STUDY_DIRECTOR
References:
citation: Klimo P Jr, Kestle JR, MacDonald JD, Schmidt RH. Marked reduction of cerebral vasospasm with lumbar drainage of cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg. 2004 Feb;100(2):215-24. doi: 10.3171/jns.2004.100.2.0215.
citation: Al-Tamimi YZ, Bhargava D, Feltbower RG, Hall G, Goddard AJ, Quinn AC, Ross SA. Lumbar drainage of cerebrospinal fluid after aneurysmal subarachnoid hemorrhage: a prospective, randomized, controlled trial (LUMAS). Stroke. 2012 Mar;43(3):677-82. doi: 10.1161/STROKEAHA.111.625731. Epub 2012 Jan 26.