Transdermal Nicotine Replacement in Smokers With Acute Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Transdermal Nicotine Replacement in Smokers With Acute Aneurysmal Subarachnoid Hemorrhage

Conditions
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Aneurysmal Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: Nicotine (transdermal)


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NRT<br>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)<br>* Application of transdermal nicotine replacement in smokers with acute aneurysmal hemorrhage<br>* Other names: Nicotinelle;|
| No Intervention: no NRT<br>Active smokers with acute aneurysmal hemorrhage that were assigned to not receive transdermal nicotine replacement. | |
| No Intervention: non-smokers<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aneurysm, nicotine replacement therapy, cerebral vasospasm, outcome