Induced Hypertension for Treatment of Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage

NCT ID: NCT01613235

Last Updated: 2017-11-06

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

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-31

Study Completion Date

2015-12-10

Brief Summary

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The objective of this multi-centre, randomized controlled trial is to investigate the outcome after induced hypertension versus no induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH), 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

Subarachnoid haemorrhage (SAH) from a ruptured cerebral aneurysm is a subset of stroke with a poor prognosis. Delayed cerebral ischemia (DCI) is a major complication after SAH in around 30% of SAH patients and increases case fatality 1.5 - 3 fold. One option to treat DCI is to use induced hypertension, alone or in combination with haemodilution and hypervolemia, so called Triple-H, but the efficacy of induced hypertension in reducing DCI is based on case series only, and not on a randomised clinical trial.

Objective

To investigate the outcome after induced hypertension versus no induced hypertension in patients with DCI after aneurysmal SAH.

Study design

A multi-centre, single blinded, randomized controlled trial.

Study population

Patients admitted to one of the participating centres after recent SAH with a treated aneurysm and DCI based on the onset of a new focal deficit and/or a decrease of the level of consciousness of at least 1 point of the Glasgow Coma Scale with exclusion of other causes of deterioration, will be randomized to either hypertension (n=120) or no hypertension (n=120).

Interventions

Patients in arm 1 will have their blood pressure raised in order to improve cerebral blood flow (CBF). In case of a low cardiac output, inotropics will be added. Induced hypertension will be continued for at least 48 hours when patients show some improvement within the first 24 hours. After 48 hours, the dose of vasopressor will be tapered daily, and resumed in case of clinical deterioration. In patients who do not show any improvement within 24 hours, induced hypertension will not be continued. In patients in arm 2 of the trial, hypertension will not be induced. Patients in both arms of the trial will be treated with oral nimodipine and normovolaemia without haemodilution. In some selected centres, an extra perfusion CT scan is performed 24-36 hours after instalment of the treatment. 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.

Main outcome measurement

The modified Rankin scale at 3 months after the SAH, will be compared between patients who were randomized to induced hypertension and patients who were randomized to no induced hypertension.

Conditions

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Cerebral Ischemia Subarachnoid Hemorrhage

Keywords

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subarachnoid hemorrhage ischemia vasospasm CT perfusion induced hypertension delayed cerebral ischemia

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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No intervention

No induced hypertension (reference group)

Group Type NO_INTERVENTION

No interventions assigned to this group

Induced hypertension

Patients who are randomised to this arm will have their blood pressure raised with vasopressors and fluids. Blood pressure will be raised in order to improve cerebral blood flow (CBF). In case of a low cardiac output, inotropics will be added. Induced hypertension will be continued for at least 48 hours when patients show some improvement within the first 24 hours. After 48 hours, the dose of vasopressor will be tapered daily, and resumed in case of clinical deterioration. In patients who do not show any improvement within 24 hours, induced hypertension will not be continued.

Group Type ACTIVE_COMPARATOR

Induced hypertension

Intervention Type OTHER

Blood pressure will be raised in order to improve cerebral blood flow (CBF). In case of a low cardiac output, inotropics will be added. Induced hypertension will be continued for at least 48 hours when patients show some improvement within the first 24 hours. After 48 hours, the dose of vasopressor will be tapered daily, and resumed in case of clinical deterioration. In patients who do not show any improvement within 24 hours, induced hypertension will not be continued.

Interventions

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Induced hypertension

Blood pressure will be raised in order to improve cerebral blood flow (CBF). In case of a low cardiac output, inotropics will be added. Induced hypertension will be continued for at least 48 hours when patients show some improvement within the first 24 hours. After 48 hours, the dose of vasopressor will be tapered daily, and resumed in case of clinical deterioration. In patients who do not show any improvement within 24 hours, induced hypertension will not be continued.

Intervention Type OTHER

Other Intervention Names

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Hypertension. Raised blood pressure.

Eligibility Criteria

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Inclusion Criteria

1. Admission to one of the participating study centres.
2. Age 18 years or over.
3. SAH with an aneurysmatic bleeding pattern.


1. Informed consent to participate in the proposed trial when DCI will develop.
2. DCI based on a decrease of at least one point on the Glasgow Coma Scale sum score unless the decrease doesn't reflect DCI as evaluated by the treating physician, and/or the development of new focal neurological deficits, diagnosed by a neurologist, neurosurgeon or intensivist.

Exclusion Criteria

1. Evidence of DCI after the SAH, defined as any decrease in the level of consciousness or the development of new focal neurological deficits after the onset of the SAH that is not due to increasing hydrocephalus, rebleeding of the aneurysm, epileptic seizure, septic- or metabolic encephalopathy, unless symptoms of DCI started within 3 hours.
2. Co-existing severe head injury.
3. Perimesencephalic haemorrhage (perimesencephalic bleeding pattern and no aneurysm on CT-angiography).
4. A history of a ventricular cardiac rhythm disorder, necessitating medical treatment.
5. A history of a left ventricular heart failure, necessitating medical treatment.
6. Likely transfer to another hospital, not participating in the trial, soon after treatment for the aneurysm.
7. Moribund.
8. Pregnancy.

And furthermore, in selected centres where the sub study with CT perfusion will be performed:
9. Known allergy for CT-contrast agents.
10. Renal failure, defined as a serum creatinine \> 150 µmol/l, because of the risk of contrast nephropathy.
11. Diabetes mellitus.


1. Another cause for neurological deterioration including.
2. A symptomatic aneurysm not yet treated by coiling or clipping.
3. Severe hypertension, defined as a spontaneous MAP of 120 mmHg or more at the moment of evaluation for trial participation.
4. Any contraindication for induced hypertension (such as a cardiac complication necessitating medical treatment) as evaluated by the treating physician.

And furthermore, in selected centres where the sub study with CT perfusion will be performed:
5. No CTP scan at time of neurological deterioration.
6. More than 3 CTP scans since admission.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role lead

Responsible Party

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A.J.C. Slooter

MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Arjen Slooter, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

AMC Amsterdam and UMC Utrecht

Walter van den Bergh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

AMC Amsterdam and UMC Groningen

Locations

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Academic Medical Centre Amsterdam

Amsterdam, North Holland, Netherlands

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

Countries

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Netherlands

References

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Gathier CS, van der Jagt M, van den Bergh WM, Dankbaar JW, Rinkel GJE, Slooter AJC; HIMALAIA Study Group. Slow recruitment in the HIMALAIA study: lessons for future clinical trials in patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on feasibility data. Pilot Feasibility Stud. 2022 Aug 30;8(1):193. doi: 10.1186/s40814-022-01155-4.

Reference Type DERIVED
PMID: 36042527 (View on PubMed)

Gathier CS, van den Bergh WM, van der Jagt M, Verweij BH, Dankbaar JW, Muller MC, Oldenbeuving AW, Rinkel GJE, Slooter AJC; HIMALAIA Study Group. Induced Hypertension for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. Stroke. 2018 Jan;49(1):76-83. doi: 10.1161/STROKEAHA.117.017956. Epub 2017 Nov 20.

Reference Type DERIVED
PMID: 29158449 (View on PubMed)

Gathier CS, Dankbaar JW, van der Jagt M, Verweij BH, Oldenbeuving AW, Rinkel GJ, van den Bergh WM, Slooter AJ; HIMALAIA Study Group. Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial. Stroke. 2015 Nov;46(11):3277-81. doi: 10.1161/STROKEAHA.115.010537. Epub 2015 Oct 6.

Reference Type DERIVED
PMID: 26443829 (View on PubMed)

Gathier CS, van den Bergh WM, Slooter AJ; HIMALAIA-Study Group. HIMALAIA (Hypertension Induction in the Management of AneurysmaL subArachnoid haemorrhage with secondary IschaemiA): a randomized single-blind controlled trial of induced hypertension vs. no induced hypertension in the treatment of delayed cerebral ischemia after subarachnoid hemorrhage. Int J Stroke. 2014 Apr;9(3):375-80. doi: 10.1111/ijs.12055. Epub 2013 May 22.

Reference Type DERIVED
PMID: 23692645 (View on PubMed)

Other Identifiers

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10/157

Identifier Type: -

Identifier Source: org_study_id