Evaluation of Transdermal Nicotine on Delayed Gastric Emptying Post-Pancreatoduodenectomy: A Randomized, Double-Blind, Placebo-Controlled Multicenter Trial

The primary objective of this study is to assess the effect of **transcutaneous administration of nicotine** compared to placebo on the development and severity of delayed gastric emptying (DGE) following pancreatoduodenectomy. This is clinically relevant as DGE is a common complication after pancreatoduodenectomy, impacting patient recovery and prolonging hospital stays. Understanding the potential benefits of nicotine in this context could lead to improved postoperative outcomes and patient management strategies.

Secondary objectives include evaluating the safety, efficacy, and tolerability of transcutaneous nicotine administration compared to placebo in patients undergoing pancreatoduodenectomy. These assessments are crucial for determining the overall viability of nicotine as a therapeutic option in this surgical setting.

The clinical trial involves participants who are scheduled to undergo **pancreatoduodenectomy**. The study population includes both male and female subjects aged 18 years and older. Participants are required to have provided written informed consent to partake in the trial. The trial does not involve a vulnerable population. Smokers among the participants must be willing to cease smoking for the duration of the investigational medicinal product application, specifically from Day 1 to Day 7. The sponsor has not provided information regarding the total number of participants in the trial. The selection criteria ensure that the study population is representative of individuals undergoing the specified surgical procedure, with considerations for lifestyle factors such as smoking habits.

The clinical trial is designed to evaluate the effect of **transcutaneous nicotine** administration on the development and severity of delayed gastric emptying following pancreatoduodenectomy. This study is a randomized, placebo-controlled, double-blind, multicenter trial. The trial is expected to commence recruitment on July 1, 2023, and conclude by July 31, 2025. Participants will be randomly assigned to receive either the active treatment, Nicotinell 14 mg/24-Stunden-Pflaster, or a placebo. The primary endpoint is the grade of delayed gastric emptying, assessed according to the International Study Group of Pancreatic Surgery's criteria. Secondary endpoints include postoperative pancreatic fistula, postpancreatectomy hemorrhage, and other postoperative complications.

Study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will confirm eligibility based on criteria such as age (≥18 years), consent, and planned pancreatoduodenectomy. Smokers must agree to abstain from smoking during the intervention period. Follow-up visits will monitor the participants' health status and adherence to the study protocol. The end-of-study visit will evaluate the final outcomes and any adverse events. The total duration of participant involvement is approximately seven days, corresponding to the maximum treatment period with the transdermal patch.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with the study protocol, or withdraw consent. The trial is conducted under Phase IV, indicating a post-marketing surveillance phase to explore therapeutic effects further. The study aims to provide valuable insights into the management of delayed gastric emptying in patients undergoing pancreatoduodenectomy, contributing to improved postoperative care and patient outcomes.

The clinical trial involves the use of **Nicotinell 14 mg / 24-Stunden-Pflaster**, a transdermal patch containing **nicotine** as the active substance. This experimental medication is designed for **transdermal use**, allowing the nicotine to be absorbed through the skin. The patch is applied once every 24 hours, delivering a maximum daily dose of 14 mg of nicotine. The treatment period with this patch is limited to a maximum of 7 days. The nicotine used in this patch is of chemical origin, and the product is manufactured by GlaxoSmithKline Consumer Healthcare GmbH & Co. KG. The patch is not formulated for pediatric use.

The study also includes a **placebo** treatment, referred to as the **Patchinga Freestyle Libre 3 Patch**. This placebo is used as a comparator to assess the effect of the nicotine patch on the development and severity of delayed gastric emptying following pancreatoduodenectomy. The placebo patch does not contain any active substances and serves to maintain the double-blind nature of the trial. The pharmaceutical form and specific details regarding the administration of the placebo patch are not provided.

Efficacy in this clinical trial will be assessed by evaluating the effect of transcutaneous administration of **nicotine** compared to placebo on the development and severity of delayed gastric emptying (DGE) following pancreatoduodenectomy. The primary endpoint for efficacy assessment is the grade of delayed gastric emptying, categorized as none or grades A-C, which represent increasing severity according to the definition of the International Study Group of Pancreatic Surgery. Secondary endpoints include the occurrence of postoperative pancreatic fistula, postpancreatectomy hemorrhage, intraabdominal fluid collections, surgical site infections, re-intervention and re-operation rates, Clavien-Dindo classification, MTL30 score, quality-of-life questionnaires (QLQ-C30 and PAN26), mortality, cardiovascular events such as non-fatal myocardial infarction, non-fatal stroke, and revascularization during admission. Additionally, the requirement of a naso-gastric tube (NGT), inability to tolerate solid oral food, vomiting or gastric distension, and use of prokinetics in the first 21 days after surgery will be monitored, along with adverse events and serious adverse events.