To investigate the outcome after induced hypertension versus no induced hypertension in patients with DCI after aneurysmal SAH.
ID
Source
Brief title
Condition
- Central nervous system vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome parameter will be the proportion of SAH patients with DCI
with poor outcome three months after the SAH, defined as a modified Rankin
Scale score of 3 or more.
Secondary outcome
Secondary study parameters are related to treatment failure, functional
outcome, adverse events and to the influence on cerebral haemodynamics.
Related to treatment failure: proportion of patients in the induced
hypertension group in which induced hypertension did not give clinical
improvement of symptoms of DCI within 24 hours.
Related to the functional condition: case fatality 30 days after SAH,
Activities of daily living (ADL), three months after the SAH assessed with the
Barthel Index, Quality of life, three months after the SAH, estimated with the
Stroke Specific Quality of Life Scale (SSQoL-12-NL). Anxiety and depression,
three months after the SAH, assessed with the Hospital Anxiety and Depression
Scale (HADS). Cognitive functioning, three months after the SAH, evaluated by
the Cognitive Failures Questionnaire (CFQ). Functional outcome twelve months
after the SAH, assessed with the modified Rankin Scale.
Related to adverse effects: Complications related to insertion of a central
venous catheter or intra-arterial catheter (including local haemorrhage and
pneumothorax). Intracranial complications related to induced hypertension (such
as exacerbation of cerebral oedema, hemorrhagic infarction and bleeding of an
asymptomatic aneurysm). Systemic complications related to induced hypertension
(including cardiac rhythm disorders, low cardiac output state and cardiac
ischemia).
Related to the influence on cerebral haemodynamics: The difference in CBF, CBV,
TTP and MTT between the intervention and the control groups 24-36 hours after
the start of the study (i.e. CTP-2). The difference in CBF, CBV, TTP and MTT
between the perfusion CT-scan (at baseline, the moment of deterioration, i.e.
CTP-1) and the second perfusion CT-scan (CTP-2) within the same patients.
Background summary
Delayed cerebral ischaemia (DCI) is a major complication after aneurysmal
subarachnoid hemorrhage (SAH). The proportion of SAH patients who develop DCI
is around 30%. DCI is associated with a 1.5-3 fold higher mortality rate. Many
centers around the world use induced hypertension, alone or in combination with
haemodilution and hypervolaemia, so called Triple-H, as standard therapy in the
treatment of DCI, but the efficacy of induced hypertension in reducing DCI is
based on case series only, and not on a randomized clinical trial.
Study objective
To investigate the outcome after induced hypertension versus no induced
hypertension in patients with DCI after aneurysmal SAH.
Study design
Multi-centre, randomized, single blind, controlled clinical trial
Intervention
Group1. No induced hypertension: patients will not be treated with induced
hypertension when DCI develops. Hypotension (mean arterial pressure (MAP) below
80 mmHg) will be prevented. In order to achieve this, vasopression will be
applied according to the protocol of the participating centre.
Group 2. Induced hypertension group: increasing the blood pressure with
vasopressors as described in the protocol of the participating centre until
clinical improvement is observed. The maximum MAP in these patients will be 130
mmHg and the maximum systolic blood pressure 230 mmHg. If there is no clinical
improvement observed within 24 hours after reaching one of the above mentioned
maximum values the administration of vasopressors will be tapered (according to
the protocol of the participating centre). If clinical improvement is seen
within 24 hours after the start of induced hypertension, induced hypertension
will be continued for 48 hours, after which attempt will be made to lower the
vasopression slowly. The vasopression will be restarted when, at such a point,
clinical worsering happens.
Study burden and risks
Patients will be randomised into two groups. The induced hypertension group
will undergo induced hypertension. The medical and nursing staff has large
experience with induced hypertension and the patient will be monitored
continuously at the ICU or Medium Care Unit. Patients in the no induced
hypertensiongroup will not have their blood pressure highered.
In selected centres, where a substudy will be performed on the influence of
induced hypertension on cerebral haemodynamics by means of CT perfusion scan,
the risk excists of allergic reaction to CT contrast when this was not known
priorly. Furthermore, patients are submitted to radiation.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Admission to the hospital 2. Age 18 years or over 3. Aneurysmal SAH, demonstrated on CT-angiography or cerebral angiograph 4. DCI (decrease of at least one point on the GSC sumscore, unless the decrease doesn*t reflect DCI as evaluated by the treating physician, and/or all new neurological focal deficits), diagnosed by a neurologist, neurosurgeon or intensivist, 5. Informed consent
Exclusion criteria
0. Evidence of DCI after the SAH at time of asking for informed consent, unless symptoms of DCI started within 3 hours 1. Co-existing severe head injury. 2. A perimesencephalic haemorrhage. 3. A history of a ventricular cardiac rhythm disorder, necessitating medical treatment. 4. A history of left ventricular heart failure, necessitating medical treatment. 5. Pregnancy. 6. Transferral to another hospital, 7. moribund, 8. Other cause for neurological deterioration (see page 19 of the study protocol for the differential diagnosis) 9. Symptomatic cerebral aneurysm not yet treated by coiling or clipping, 10. Severe hypertension, defined as a spontaneous MAP of 120 mmHg or more at the moment of evaluation for trial participation, 11. Any contraindication for induced hypertension (such as a cardiac complication necessitating medical treatment) as evaluated by the treating physician. And furthermore, in selected centres where the sub study with CT perfusion will be performed: 12. known allergy for CT-contrast agents. 13. renal failure, defined as a serum creatinine > 150 µmol/l, because of the risk of contrast nephropathy. 14. diabetes mellitus.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01613235 |
| CCMO | NL32978.018.10 |