Evaluation of the Analgesic Efficacy and Safety of Clonidine Hydrochloride in Postoperative Pain Management Following Colectomy in Cancer Patients

The primary objective of this placebo-controlled, double-blind trial is to evaluate the **analgesic** effect and safety of a single intravenous bolus dose of **clonidine hydrochloride** administered postoperatively to patients undergoing colectomy due to cancer. The study aims to determine the relationship between clonidine administration and the management of postoperative acute pain following major abdominal surgery. This is clinically relevant as effective pain management is crucial for patient recovery and can potentially reduce the need for additional analgesics, thereby minimizing associated side effects and improving overall patient outcomes.

The clinical trial involves participants who are undergoing a **colectomy** due to cancer. The study population includes both male and female subjects, aged over 18 years, who are in general good health and are not considered part of a vulnerable population. The total number of participants has not been disclosed by the sponsor. Participants were selected based on their planned colectomy due to cancer, their ability to read and understand Danish, and their willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. No specific lifestyle considerations such as diet or physical activity are highlighted in the trial details.

The clinical trial is designed as a **placebo-controlled**, **double-blind** study to evaluate the analgesic effect and safety of **clonidine hydrochloride** in patients undergoing colectomy due to cancer. The trial will assess the relationship between a single intravenous bolus dose of clonidine administered postoperatively and the management of acute postoperative pain. The study is categorized as a phase IV, low-intervention clinical trial, with an estimated recruitment start date of November 15, 2024, and an anticipated end date of February 14, 2028.

Participants will be randomly assigned to receive either clonidine or a placebo, with both groups receiving the treatment intravenously. The primary endpoint is the use of morphine 24 hours post-operatively, while secondary endpoints include pain scores (VAS/NRS), quantitative sensory testing, autonomic nervous system parameters (blood pressure, ECG, heart rate, saturation, temperature, pupil reaction), genetic profiling, and blood sample analysis for drug concentrations. The trial will also collect demographic, physical, medical, and laboratory data, along with conducting physical examinations.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are confirmed, including planned colectomy due to cancer, age over 18 years, and the ability to read and understand Danish. Participants must also demonstrate willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. Follow-up visits will be conducted to monitor the participants' response to the treatment and collect necessary data. The end-of-study visit will conclude the trial, ensuring all data is collected and any adverse events are addressed.

The expected length of participant involvement is approximately one day, corresponding to the administration of the treatment and the subsequent 24-hour monitoring period. Conditions that may lead to early termination from the study include non-compliance with the trial protocol, withdrawal of consent, or any adverse events that compromise participant safety. The trial aims to provide valuable insights into the efficacy and safety of clonidine in managing postoperative pain in patients undergoing major abdominal surgery.

The clinical trial involves the administration of **clonidine hydrochloride**, a chemical compound with the active substance name **CLONIDINE**. The pharmaceutical form of clonidine used in this study is identified by the code PHF00082MIG. Clonidine is administered intravenously, with a maximum daily dose of 750 micrograms. The total dose administered does not exceed 750 micrograms, and the treatment period is limited to a single day. Clonidine is utilized for its analgesic, sedative, and blood pressure-lowering properties. The administration of clonidine is conducted in a controlled environment to ensure participant safety and adherence to the dosing schedule.

In addition to clonidine, the study employs a non-experimental treatment in the form of isotonic or physiological saline, which serves as a placebo. This placebo is administered intravenously, with a maximum daily dose of 5 milliliters, and the total dose does not exceed 5 milliliters. The pharmaceutical form of the saline solution is identified by the code PHF00017MIG. The use of a placebo is integral to maintaining the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. Compliance with the dosing schedule and administration protocols is closely monitored to maintain the integrity of the trial data.

Efficacy in this clinical trial will be assessed through both primary and secondary endpoints. The primary endpoint is the use of morphine 24 hours post-operatively, which will serve as a direct measure of the analgesic effect of **clonidine hydrochloride** administered intravenously to patients after major abdominal surgery. Secondary endpoints include a variety of measures such as VAS/NRS pain scores, questionnaires, and Quantitative Sensory Testing (QST). Additionally, autonomic nervous system parameters such as blood pressure, ECG, heart rate, oxygen saturation, temperature, and pupil reaction will be monitored. Genetic profiling will be conducted to assess certain genetic markers, including CYP2D6, OPRM, and COMT sequences, as well as SNPs of ABCB1 and rs2952768/CREB1 and ncRNA. Blood samples will be analyzed for concentrations of clonidine, morphine, and its metabolites morphine-3-glucuronide and morphine-6-glucuronide. Demographic, physical, medical, and laboratory data will also be collected, alongside physical examinations.