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

Terminated

Phase 3 Results N/A

Trial Description

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.

Trial Stopped: Our RCT recently started. The RCT is similar to the feasibility trial, so it was terminated to avoid 2 trials running simultaniously.

Conditions

Interventions

  • Norepinephrine Drug
    Intervention Desc: is a catecholamine with dual roles as a hormone and a neurotransmitter. When norepinephrine acts as a drug it will increase blood pressure by its prominent increasing effects on the vascular tone from α-adrenergic receptor activation. The resulting increase in vascular resistance triggers a compensatory reflex that overcomes its direct stimulatory effects on the heart, called the baroreceptor reflex, which results in a drop in heart rate called reflex bradycardia.
  • Induced hypertension with norepinephrine Drug
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: 2
    Description: Induced hypertension with a target MAP of 15 mmHg above the average MAP on the previous day; during 24-36 hours, until a perfusion CT scan has been performed
    ARM 2: Kind: Experimental
    Label: 3
    Description: Induced hypertension with a target MAP of 15 mmHg above the average MAP on the previous day; during 60-84 hours, until another perfusion CT has been made
    ARM 3: Kind: Experimental
    Label: 4
    Description: 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
    ARM 4: Kind: Experimental
    Label: 5
    Description: Induced hypertension with a MAP of 30 mmHg above the average MAP on the previous day; during 60-84 hours, until another perfusion CT has been made.

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Outcomes Assessor)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients in the intervention groups are treated with induced hypertension (either 15 or 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. 24-36 hours after instalment of the treatment, a perfusion CT scan is performed, and participants in the two hypertension arms of the trial either continue with induced hypertension until 60-84 hours after the start of the study, or to ceasing hypertension. 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), after 24-36 hours and at the end of the study, after 60-84 hours.

Outcomes

Type Measure Time Frame Safety Issue
Primary 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, within 18 months after the start of the study.
Secondary Related to the inclusion, to the influence on cerebral haemodynamics, to the neurological condition and to adverse events
Primary 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. duration of the trial Yes

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