Inhaled Nitric Oxide Treatment for Aneurysmal SAH Patients With Intractable Cerebral Vasospasm

NCT04988932 | Completed

• 1 other identifier: 019/10
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare but severe subtype of stroke with high mortality and morbidity. Besides rebleeding, delayed cerebral ischaemia and cerebral vasospasm (CVS) are thought to be major reasons for the poor outcome in survivors of aSAH. Despite advances in the detection and treatment of CVS 20-40% of CVS patients experience cerebral Ischaemia. Experimental animal studies for ischaemic stroke, traumatic brain injury, and SAH showed that inhaled nitric oxide (iNO) selectively dilates cerebral arteries and arterioles in hypoperfused brain tissue. The investigators therefore performed this prospective pilot study to evaluate the effects of iNO on cerebral perfusion in patients with refractory vasospasm after aSAH.

Conditions

SAH; Inhaled Nitric Oxide; Cerebral Ischemia; Vasospasm

Outcome Measures

Primary Outcomes (4)

• Improvement of severe vasospasm in digital subtraction angiography

  \> 10% increase in diameter of the vasospastic target vessel compared to baseline

  Up to 5 days

• Improvement of severe vasospasm in tissue oxygen partial pressure (PtiO2)

  An increase of more than 5 mmHg with constant fraction of inspired oxygen (FiO2)

  Up to 5 days

• Improvement of severe vasospasm in transcranial Doppler

  A decrease of more than 30 cm/s

  Up to 5 days

• Improvement of severe vasospasm in CT perfusion

  A reduction in the number of Region of interest with impaired perfusion (MTT \> 6·5 s)

  Day 2

Secondary Outcomes (2)

• Intracranial pressure

  Up to 5 days

• Assessment of ischaemic events by CT Scan

  12 weeks after SAH

Study Arms (1)

Administration of iNO in SAH patients with severe vasospasm

EXPERIMENTAL

iNO is started at a dose of 1 parts per million (ppm) and increased stepwise to 2 ppm, 5 ppm, 12 ppm, 25 ppm, until a maximum dose of 40 ppm is reached.

Drug: Inhaled nitric oxide

Interventions

Inhaled nitric oxide DRUG

Each increase of iNO dose is followed by a 10-minute monitoring period and a DSA examination. After reaching the highest effective dose of iNO or the maximum of 40 ppm another DSA is performed. iNO is going to be continued until normalisation of CVS or for a maximum period of 5 days. During iNO treatment a DSA will be performed every 24 hours, followed by a decrease of iNO to the next-lower level. If tapering the iNO concentration is associated with increasing vasospasm, iNO is going to be increased again to the last effective dosage. For cessation of iNO administration, dosage will be tapered every 30 minutes using the same dosage steps as for initiation of iNO treatment. If the duration of iNO treatment will be more than 32 hours, tapering intervals are prolonged to 4 hours. Cessation of iNO will be followed by a DSA.

Administration of iNO in SAH patients with severe vasospasm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aSAH of all severities
• Aneurysm treated by either surgical clipping or endovascular coiling
• Age between 18 - 80 years
• Proven CVS
• Cerebral hypoperfusion and neurological deficit despite treatment (oral nimodipine, induced hypertension, hypervolaemia, central venous pressure \> 6 mmHg)
• A negative pregnancy test in women
• Signed informed consent from the next of kin and an independent physician

You may not qualify if:

• Unsecured aneurysm
• Cerebral infarction on imaging in the downstream brain parenchyma of spastic vessel
• Cerebral herniation
• Intracranial pressure \> 25 mmHg
• Pregnancy
• Mean arterial pressure ≤ 90 mmHg despite catecholamines

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

Department of Neurosurgery, University Hospital Bern

Bern, 3010, Switzerland

Location

Related Publications (6)

• Terpolilli NA, Feiler S, Dienel A, Muller F, Heumos N, Friedrich B, Stover J, Thal S, Scholler K, Plesnila N. Nitric oxide inhalation reduces brain damage, prevents mortality, and improves neurological outcome after subarachnoid hemorrhage by resolving early pial microvasospasms. J Cereb Blood Flow Metab. 2016 Dec;36(12):2096-2107. doi: 10.1177/0271678X15605848. Epub 2015 Nov 2.

  PMID: 26661144 BACKGROUND

• Terpolilli NA, Kim SW, Thal SC, Kataoka H, Zeisig V, Nitzsche B, Klaesner B, Zhu C, Schwarzmaier S, Meissner L, Mamrak U, Engel DC, Drzezga A, Patel RP, Blomgren K, Barthel H, Boltze J, Kuebler WM, Plesnila N. Inhalation of nitric oxide prevents ischemic brain damage in experimental stroke by selective dilatation of collateral arterioles. Circ Res. 2012 Mar 2;110(5):727-38. doi: 10.1161/CIRCRESAHA.111.253419. Epub 2011 Dec 29.

  PMID: 22207711 BACKGROUND

• Terpolilli NA, Brem C, Buhler D, Plesnila N. Are We Barking Up the Wrong Vessels? Cerebral Microcirculation After Subarachnoid Hemorrhage. Stroke. 2015 Oct;46(10):3014-9. doi: 10.1161/STROKEAHA.115.006353. Epub 2015 Jul 7. No abstract available.

  PMID: 26152299 BACKGROUND

• Terpolilli NA, Kim SW, Thal SC, Kuebler WM, Plesnila N. Inhaled nitric oxide reduces secondary brain damage after traumatic brain injury in mice. J Cereb Blood Flow Metab. 2013 Feb;33(2):311-8. doi: 10.1038/jcbfm.2012.176. Epub 2012 Nov 28.

  PMID: 23188422 BACKGROUND

• Germann P, Braschi A, Della Rocca G, Dinh-Xuan AT, Falke K, Frostell C, Gustafsson LE, Herve P, Jolliet P, Kaisers U, Litvan H, Macrae DJ, Maggiorini M, Marczin N, Mueller B, Payen D, Ranucci M, Schranz D, Zimmermann R, Ullrich R. Inhaled nitric oxide therapy in adults: European expert recommendations. Intensive Care Med. 2005 Aug;31(8):1029-41. doi: 10.1007/s00134-005-2675-4. Epub 2005 Jun 23.

  PMID: 15973521 BACKGROUND

• Griffiths MJ, Evans TW. Inhaled nitric oxide therapy in adults. N Engl J Med. 2005 Dec 22;353(25):2683-95. doi: 10.1056/NEJMra051884. No abstract available.

  PMID: 16371634 BACKGROUND

MeSH Terms

Conditions

Brain Ischemia

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Juergen Beck, MD

  Inselspital Bern, Department of Neurosurgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Administration of iNO in SAH patients with severe vasospasm

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: August 4, 2021
• Study Start: July 31, 2012
• Primary Completion: July 28, 2019
• Study Completion: March 20, 2020
• Last Updated: August 4, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)