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

NCT01613235 | Terminated Phase 3 DMC

• 1 other identifier: 10/157
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Cerebral Ischemia; Subarachnoid Hemorrhage

Keywords

subarachnoid hemorrhage; ischemia; vasospasm; CT; perfusion; induced hypertension; delayed cerebral ischemia

Outcome Measures

Primary Outcomes (1)

• 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.

  assessed three months after the SAH

Secondary Outcomes (12)

• 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

  24 hours after start of induced hypertension

• Related to the functional condition: Case fatality 30 days after SAH

  30 days per patient

• Related to the functional condition, activities of daily living (ADL), three months after the SAH assessed with the Barthel Index.

  assessed 3 months after the SAH

• 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).

  assessed 3 months after the SAH

• Related to the functional condition: anxiety and depression, three months after the SAH, assessed with the Hospital Anxiety and Depression Scale (HADS).

  assessed 3 months after the SAH

Study Arms (2)

No intervention

NO INTERVENTION

No induced hypertension (reference group)

Induced hypertension

ACTIVE COMPARATOR

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

Interventions

Induced hypertension 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.

Also known as: Hypertension., Raised blood pressure.

Induced hypertension

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Co-existing severe head injury.
• Perimesencephalic haemorrhage (perimesencephalic bleeding pattern and no aneurysm on CT-angiography).
• A history of a ventricular cardiac rhythm disorder, necessitating medical treatment.
• A history of a left ventricular heart failure, necessitating medical treatment.
• Likely transfer to another hospital, not participating in the trial, soon after treatment for the aneurysm.
• Moribund.
• Pregnancy.
• And furthermore, in selected centres where the sub study with CT perfusion will be performed:
• Known allergy for CT-contrast agents.
• Renal failure, defined as a serum creatinine \> 150 µmol/l, because of the risk of contrast nephropathy.
• Diabetes mellitus.
• Informed consent to participate in the proposed trial when DCI will develop.
• 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.
• Another cause for neurological deterioration including.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (2)

Academic Medical Centre Amsterdam

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (4)

• 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.

  PMID: 36042527 DERIVED

• 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.

  PMID: 29158449 DERIVED

• 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.

  PMID: 26443829 DERIVED

• 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.

  PMID: 23692645 DERIVED

MeSH Terms

Conditions

Brain Ischemia; Subarachnoid Hemorrhage; Ischemia

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Hemorrhages; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Arjen Slooter, MD, PhD

  AMC Amsterdam and UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Walter van den Bergh, MD, PhD

  AMC Amsterdam and UMC Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: June 1, 2012
• First Posted: June 7, 2012
• Study Start: August 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: December 10, 2015
• Last Updated: November 6, 2017

Record last verified: 2017-11

Locations

NL (2)