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

This study has been terminated.
(Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.)
Sponsor:
Collaborator:
Netherlands Organisation for Scientific Research
Information provided by (Responsible Party):
A.J.C. Slooter, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00841633
First received: October 10, 2008
Last updated: October 11, 2011
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
Cerebral Ischemia
Subarachnoid Hemorrhage
Drug: Induced hypertension with norepinephrine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Induced Hypertension for Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage:a Feasibility Study

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 15
Study Start Date: February 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00841633

Locations
Netherlands
UMC Utrecht
Utrecht, Netherlands, 3508GA
Sponsors and Collaborators
UMC Utrecht
Netherlands Organisation for Scientific Research
  More Information

No publications provided

Responsible Party: A.J.C. Slooter, dr. A.J.C. Slooter, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00841633     History of Changes
Other Study ID Numbers: 08-137
Study First Received: October 10, 2008
Last Updated: October 11, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
subarachnoid hemorrhage
ischemia
vasospasm
CT
perfusion
induced hypertension
delayed cerebral ischemia

Additional relevant MeSH terms:
Hypertension
Ischemia
Hemorrhage
Subarachnoid Hemorrhage
Cerebral Infarction
Brain Ischemia
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Intracranial Hemorrhages
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Infarction
Stroke
Norepinephrine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014