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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor:
Information provided by (Responsible Party):
A.J.C. Slooter, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier:
NCT01613235
First received: June 1, 2012
Last updated: June 6, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Cerebral Ischemia
Subarachnoid Hemorrhage
Other: Induced hypertension
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 Treatment of Delayed Cerebral Ischaemia After Aneurysmal Subarachnoid Haemorrhage

Resource links provided by NLM:


Further study details as provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):

Primary Outcome Measures:
  • The main outcome measurement will be the modified Rankin scale at 3 months after the SAH, compared between patients who were randomized to induced hypertension and patients who were randomized to no induced hypertension. [ Time Frame: assessed three months after the SAH ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Related to treatment failure: proportion of patients in the induced hypertension group in which induced hypertension did not give clinical improvement of symptoms of DCI within 24 hours [ Time Frame: 24 hours after start of induced hypertension ] [ Designated as safety issue: No ]
  • Related to the functional condition: Case fatality 30 days after SAH [ Time Frame: 30 days per patient ] [ Designated as safety issue: Yes ]
  • Related to the functional condition, activities of daily living (ADL), three months after the SAH assessed with the Barthel Index. [ Time Frame: assessed 3 months after the SAH ] [ Designated as safety issue: No ]
  • Related to the functional condition: quality of life, three months after the SAH, estimated with the Stroke Specific Quality of Life Scale (SSQoL-12-NL). [ Time Frame: assessed 3 months after the SAH ] [ Designated as safety issue: No ]
  • Related to the functional condition: anxiety and depression, three months after the SAH, assessed with the Hospital Anxiety and Depression Scale (HADS). [ Time Frame: assessed 3 months after the SAH ] [ Designated as safety issue: No ]
  • Related to the functional condition: cognitive functioning, three months after the SAH, evaluated by the Cognitive Failures Questionnaire (CFQ). [ Time Frame: assessed 3 months after the SAH ] [ Designated as safety issue: No ]
  • Related to adverse effects: complications related to insertion of a central venous catheter or intra-arterial catheter (including local haemorrhage and pneumothorax). [ Time Frame: during hospital admission, an average of 3 weeks ] [ Designated as safety issue: Yes ]
  • Related to adverse effects: intracranial complications related to induced hypertension (such as exacerbation of cerebral oedema, hemorrhagic infarction and bleeding of an asymptomatic aneurysm). [ Time Frame: during admission, an average of 3 weeks ] [ Designated as safety issue: Yes ]
  • Related to adverse effects± • Systemic complications related to induced hypertension (including cardiac rhythm disorders, low cardiac output state and cardiac ischemia). [ Time Frame: during admission, an average of 3 weeks ] [ Designated as safety issue: Yes ]
  • In selected centres: Related to the influence on cerebral haemodynamics: the difference in CBF, CBV, TTP and MTT between the intervention and the control groups 24-36 hours after the start of the study (i.e. CTP-2) [ Time Frame: compared between scans made during admission at time of deterioration and 36 hours later. ] [ Designated as safety issue: No ]
  • Related to the influence on cerebral haemodynamics: the difference in CBF, CBV, TTP and MTT between the perfusion CT-scan (at baseline, the moment of deterioration, i.e. CTP-1) and the second perfusion CT-scan (CTP-2) within the same patients. [ Time Frame: compared between scans made during admission at time of deterioration and 36 hours later. ] [ Designated as safety issue: No ]
  • Direct medical costs of used health care resources and indirect, non-medical costs of lost productivity, will be compared between the two arms of the trial, twelve months after the SAH. [ Time Frame: assessed at 12 months after the SAH ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: August 2010
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: No intervention
No induced hypertension (reference group)
Active Comparator: 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.
Other: 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.
Other Names:
  • Hypertension.
  • Raised blood pressure.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for eligibility

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

Exclusion criteria for eligibility

  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.

Inclusion criteria for trial participation

  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 for trial participation:

  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.
  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: NCT01613235

Contacts
Contact: Celine Gathier, MD +3188-75561124 c.s.gathier-2@umcutrecht.nl

Locations
Netherlands
Academic Medical Centre Amsterdam Recruiting
Amsterdam, Noord Holland, Netherlands, 1105AZ
Universitair Medisch Centrum Utrecht Recruiting
Utrecht, Netherlands, 3584 CX
Sub-Investigator: Celine Gathier, Drs.         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Arjen Slooter, MD, PhD AMC Amsterdam and UMC Utrecht
Principal Investigator: Walter van den Bergh, MD, PhD AMC Amsterdam
  More Information

No publications provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: A.J.C. Slooter, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT01613235     History of Changes
Other Study ID Numbers: 10/157
Study First Received: June 1, 2012
Last Updated: June 6, 2012
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
subarachnoid hemorrhage
ischemia
vasospasm
CT
perfusion
induced hypertension
delayed cerebral ischemia

Additional relevant MeSH terms:
Hypertension
Brain Ischemia
Cerebral Infarction
Hemorrhage
Ischemia
Subarachnoid Hemorrhage
Brain Diseases
Brain Infarction
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Intracranial Hemorrhages
Nervous System Diseases
Pathologic Processes
Stroke
Vascular Diseases

ClinicalTrials.gov processed this record on October 29, 2014