Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study

NCT ID: NCT00841633

Last Updated: 2011-10-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2011-04-30

Brief Summary

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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

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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.

Conditions

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Cerebral Ischemia Subarachnoid Hemorrhage

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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1

No induced hypertension (reference group)

Group Type NO_INTERVENTION

No interventions assigned to this group

2

Induced hypertension with a MAP of 30 mmHg above the average MAP on the previous day; during 24-36 hours, until a perfusion CT scan has been performed

Group Type EXPERIMENTAL

Induced hypertension with norepinephrine

Intervention Type DRUG

Hypertension will be induced with norepinephrine. Administration of norepinephrine results in vasoconstriction, leading to an increase in blood pressure. The normal blood pressure of the patient will be calculated as the average MAP of the day before the start of the study. To achieve the intended hypertension (30 mmHg above the normal MAP for patients allocated to index group 2) in most cases a dose of 100-300 ng/kg/minute must be administered. Norepinephrine will be started on a dose of 100 ng/kg/minute, after which the dosing will be adjusted to achieve the desired blood pressure level. The maximum dose to be used in the study is 1000 ng/kg/minute. Norepinephrine is administered through the central venous catheter.

Interventions

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Induced hypertension with norepinephrine

Hypertension will be induced with norepinephrine. Administration of norepinephrine results in vasoconstriction, leading to an increase in blood pressure. The normal blood pressure of the patient will be calculated as the average MAP of the day before the start of the study. To achieve the intended hypertension (30 mmHg above the normal MAP for patients allocated to index group 2) in most cases a dose of 100-300 ng/kg/minute must be administered. Norepinephrine will be started on a dose of 100 ng/kg/minute, after which the dosing will be adjusted to achieve the desired blood pressure level. The maximum dose to be used in the study is 1000 ng/kg/minute. Norepinephrine is administered through the central venous catheter.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Netherlands Organisation for Scientific Research

OTHER_GOV

Sponsor Role collaborator

UMC Utrecht

OTHER

Sponsor Role lead

Responsible Party

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A.J.C. Slooter

dr. A.J.C. Slooter

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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UMC Utrecht

Utrecht, Utrecht, Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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08-137

Identifier Type: -

Identifier Source: org_study_id