Clinical trial NCT00841633: Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study
Official title: Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cerebral Ischemia
Subarachnoid Hemorrhage
Keywords: subarachnoid hemorrhage
ischemia
vasospasm
CT
perfusion
induced hypertension
delayed cerebral ischemia
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Netherlands Organisation for Scientific Research
First posted: 2009-02-11
Enrollment: 15
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: The purpose of this study is to test the feasibility of a trial on induced hypertension to improve neurological outcome in patients with subarachnoid haemorrhage that developed the serious complication "delayed cerebral ischemia", and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.

Detailed description: Background:

Delayed cerebral ischaemia (DCI) is a major complication after aneurysmal subarachnoid haemorrhage (SAH). The proportion of SAH patients who develop DCI is around 30%. Many centres 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 randomised clinical trial.

Objective:

To test the feasibility of a trial on induced hypertension to improve neurological outcome, and to assess whether induced hypertension results in improved cerebral blood flow (CBF) as measured by means of perfusion-CT.

Study design:

A randomised controlled feasibility trial.

Study population:

Patients admitted to the UMC Utrecht after recent SAH, who develop DCI. Twenty four patients will be randomised into a standard care group or one of the intervention groups.

Interventions:

Patients in the intervention groups are treated with induced hypertension (30 mmHg increase in mean arterial pressure) in order to improve CBF. Patients in the standard care group are treated according to the standardised SAH treatment protocol of the UMC Utrecht by monitoring mean arterial pressure and preventing dropping of mean arterial pressure to under 80 mmHg. 24-36 hours after instalment of the treatment, a perfusion CT scan is performed. In patients that do not show any neurological improvement within 24 hours after starting the hypertensive treatment, the administration of norepinephrine will be tapered. In patients who show improvement, induced hypertension will be continued for a total period of 72 hours, after which norepinephrine will be gradually tapered. Measurement of CBF is performed in all participants with perfusion CT-scanning of the brain at the beginning of the study (as part of regular patient care) and after 24-36 hours after starting .

Main outcome measurement:

The number of patients with the diagnosis of DCI after SAH, in which the intervention (induced hypertension) was adequately performed, included within 18 months after the start of the study.

Eligibility criteria: Inclusion Criteria:

1. Admission to the UMC Utrecht.
2. Age 18 years or over.
3. Aneurysmal SAH, demonstrated on CT-angiography or cerebral angiography, with onset less than 72 hours before admission.
4. A level of consciousness corresponding to a Glasgow Coma Sum Score above 8, as in patients with lower Glasgow Coma Sum Scores, assessment of further deterioration may be less reliable.

Exclusion Criteria:

1. Symptomatic aneurysm not yet treated by coiling or clipping. Co-existing asymptomatic cerebral aneurysms are no reason for exclusion, since previous studies found no increased risk of rupture of such aneurysms during hypertensive and hypervolemic treatment.(26)
2. Co-existing severe head injury.
3. A history of a cardiac rhythm disorder, necessitating medical treatment.
4. A history of a left ventricular pump failure, necessitating medical treatment.
5. Pregnancy.
6. Known allergy for CT-contrast agents.
7. Renal failure, defined as a serum creatinine \> 150 µmol/l, because of the risk of contrast nephropathy.

Primary outcomes:
measure: The main study parameter will be the number of SAH patients with a diagnosis of DCI who were randomised to one of the intervention groups, in whom the intervention was adequately performed, during the duration of the trial.
timeFrame: duration of the trial
Secondary outcomes:
measure: Related to the inclusion, to the influence on cerebral haemodynamics, to the neurological condition and to adverse events
timeFrame: cerebral haemodynamics: 24-36 hours, neurological condition: 6 weeks
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
References: