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

October 11, 2011 updated by: A.J.C. Slooter, UMC Utrecht
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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
NO_INTERVENTION: 1
No induced hypertension (reference group)
EXPERIMENTAL: 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
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: duration of the trial
duration of the trial

Secondary Outcome Measures

Outcome Measure
Time Frame
Related to the inclusion, to the influence on cerebral haemodynamics, to the neurological condition and to adverse events
Time Frame: cerebral haemodynamics: 24-36 hours, neurological condition: 6 weeks
cerebral haemodynamics: 24-36 hours, neurological condition: 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UMC Utrecht

Collaborators

Netherlands Organisation for Scientific Research

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (ACTUAL)

April 1, 2011

Study Completion (ACTUAL)

April 1, 2011

Study Registration Dates

First Submitted

October 10, 2008

First Submitted That Met QC Criteria

February 10, 2009

First Posted (ESTIMATE)

February 11, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

October 12, 2011

Last Update Submitted That Met QC Criteria

October 11, 2011

Last Verified

October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-137

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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