Introduction: Nicotine is a potent anti-inflammatory alkaloid that has demonstrated modest preclinical and clinical benefit in a number of inflammatory-mediated pathologies. In the setting of intracerebral hemorrhage (ICH), inflammation is a central component of secondary injury, and nicotine administration in experimental ICH has led to significant improvements in functional outcome. Here, we sought to evaluate the safety of transdermal nicotine in a cohort of ICH patients in a phase Ib clinical trial.

Methods: This was a “3+3” dose-escalation trial. Eligibility criteria include age =18 years, radiologically confirmed diagnosis of ICH and ability to initiate transdermal nicotine patch within 72 hours of symptom onset. The first cohort of three patients received a low-dose (7-mg) transdermal nicotine patch once daily beginning on the day of enrollment and for 14 consecutive days or until hospital discharge, whichever came first. The subsequent cohort of three patients received the intermediate dose (14-mg) patch according to the same regimen, and the final cohort received the high-dose (21-mg) patch. Safety monitoring consisted of twice-daily examinations for the duration of drug administration, and a drug-safety monitoring board (DSMB) convened every three months throughout the trial.

Results: Nine patients were enrolled. The mean and median number of patches administered was 8.375 and 7, respectively. One patient experienced a non-ST elevation myocardial infarction during treatment, but this was determined by the DSMB to be unrelated to the administration of transdermal nicotine.

Conclusions: Nine patients were enrolled. The mean and median number of patches administered was 8.375 and 7, respectively. One patient experienced a non-ST elevation myocardial infarction during treatment, but this was determined by the DSMB to be unrelated to the administration of transdermal nicotine. No drug-related adverse events were experienced by any of the enrolled patients.

Patient Care: This research could lead to a phase II and/or phase III trial to evaluate nicotine as an anti-inflammatory or neuroprotectant medication in the intracerebral hemorrhage population.

Learning Objectives: By the conclusion of this session, partipants shoudl be able to: 1) discuss outcome following ICH, 2) discuss the importance of edema in ICH, and 3) identify the current treatment options in ICH

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