Transdermal Nicotine Replacement in Smokers With Acute Aneurysmal Subarachnoid Hemorrhage (NRT-SAH)

All patients with acute aneurysmal hemorrhage are treated in accordance with our institutional protocol. After securing of the aneurysm, some smokers with acute aneurysmal hemorrhage are randomly assigned to transdermal nicotine replacement (NRT). The short- and long-term effect of NRT will be studied comparing non-smokers, smokers without NRT and smokers with NRT.

Study Overview

• Status: Completed
• Conditions: Aneurysmal Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: Nicotine (transdermal)

Detailed Description

Various aspects of the study:

• Study cerebral circulation with transcranial Doppler ultrasonography (TCD) prior to and after NRT.
• Study cardiac output and peripheral vessel resistance minimally invasive (LiDCO) prior to and after NRT in patients that already have established LiDCO.
• Monitor intracranial pressure prior to and after NRT in patients that have established an intracranial pressure sensor.
• Register the frequency of cerebral vasospasm and complications in non-smokers, smokers without NRT, and smokers with NRT.
• Register the use of opioids, opioidanesthetics, propofol og psycholeptics in non-smokers, smokers without NRT, and smokers with NRT.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway, 0027
    • Oslo University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aneurysmal subarachnoid hemorrhage after securing of the aneurysm and surviving the first 2 weeks.

Exclusion Criteria:

• manifest cerebral vasospasm at arrival at our department (i.e. before securing of the aneurysm)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NRT; Active smokers with acute aneurysmal hemorrhage randomly assigned to transdermal nicotine replacement after securing of the aneurysm. Patient management for all patients is according to the institutional treatment guidelines and independent of group assignment. The dose is dependent on smoke consumption prior to the ictus. Nicorette 7 mg/day for smokers smoking 1-10 cigarettes /day Nicorette 14mg/day for smokers smoking 11-19 cigarettes/day Nicorette 21 mg/day for smokers smoking 20 or more cigarettes daily	Drug: Nicotine (transdermal); Application of transdermal nicotine replacement in smokers with acute aneurysmal hemorrhage; Other Names: Nicotinelle
No Intervention: no NRT; Active smokers with acute aneurysmal hemorrhage that were assigned to not receive transdermal nicotine replacement.
No Intervention: non-smokers; Non-smokers with acute aneurysmal hemorrhage. Non-smokers do not receive transdermal nicotine replacement. This group is to be compared to the group of active smokers receiving transdermal nicotine replacement and to the group of active smokers not receiving transdermal nicotine replacement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral vasospasm	Frequency of cerebral vasospasm within 21 days after the ictus. The institutional protocol for management of aneurysmal hemorrhage is followed in diagnosing cerebral vasospasm. This includes monitoring for cerebral vasospasm with transcranial Doppler ultrasonography and a cerebral computed tomography angiogram on day 7 after the ictus. Digital subtraction angiography is performed when necessary. All patients are monitored in the intensive care or intermediate care unit for clinical signs of cerebral vasospasm.	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smoking status	Managed to quit smoking after NRT?	1 year
Functional outcome	Glasgow outcome scale, Glasgow outcome scale extended, Rankin Stroke Scale, return to work	3 and 12 months
Drug consumption	Use of sedatives and anesthetics	as long as the patient is in the intensive care unit
Cerebral infarction	Radiological evidence of irreversible brain tissue damage. All patients have a control scan approximately 3 months after the ictus. This is either a computed tomography scan (if the patient had the aneurysm secured surgically) or a magnetic resonance image (if the patient had endovascular repair of the aneurysm)	3-6 months
Complications	Frequency of complications including secondary hydrocephalus and mortality. Special emphasis on thrombo-embolic complications (deep venous thrombosis and pulmonary embolism)	3-6 months

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Investigators: Principal Investigator: Angelika G Sorteberg, MD, PhD, Consulting neurosurgeon, Head of division Rikshospitalet

Publications and helpful links

General Publications

• Seder DB, Schmidt JM, Badjatia N, Fernandez L, Rincon F, Claassen J, Gordon E, Carrera E, Kurtz P, Lee K, Connolly ES, Mayer SA. Transdermal nicotine replacement therapy in cigarette smokers with acute subarachnoid hemorrhage. Neurocrit Care. 2011 Feb;14(1):77-83. doi: 10.1007/s12028-010-9456-9.
• Krishnamurthy S, Kelleher JP, Lehman EB, Cockroft KM. Effects of tobacco dose and length of exposure on delayed neurological deterioration and overall clinical outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2007 Sep;61(3):475-80; discussion 480-1. doi: 10.1227/01.NEU.0000290892.46954.12.
• Weir BK, Kongable GL, Kassell NF, Schultz JR, Truskowski LL, Sigrest A. Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg. 1998 Sep;89(3):405-11. doi: 10.3171/jns.1998.89.3.0405.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: January 25, 2015
• First Posted (Estimate): January 29, 2015

Study Record Updates

• Last Update Posted (Estimate): April 12, 2016
• Last Update Submitted That Met QC Criteria: April 11, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: outcome; nicotine replacement therapy; aneurysm; cerebral vasospasm
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: 2011-2561b

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No