Postoperative recovery with the addition of long-acting NK1- and 5-HT3 receptor antagonists as prophylaxis for post-operative nausea and vomiting. A prospective, double-blind, randomized trial in laparoscopic surgery.

The primary objective evaluates whether the addition of long-acting NK1 and 5-HT3 receptor antagonists to standard prophylaxis results in improved early postoperative recovery, as measured by a reduction in QoR-15swe score from baseline to postoperative day 1 (POD1) that is at least 8.0 points smaller in the intervention group compared to the control group. This assessment is clinically relevant as it quantifies the impact of enhanced antiemetic prophylaxis on overall recovery quality in patients undergoing laparoscopic surgery, a population at risk for postoperative nausea and vomiting (PONV).

The secondary objectives assess multiple dimensions of postoperative outcomes and safety:

• Comparison of QoR-15swe scores between study groups throughout the postoperative period
• Proportion of participants achieving patient-accepted symptom state (QoR-15swe > 117) on POD1, POD2, and POD3
• Incidence of PONV, nausea, vomiting, and antiemetic requirement
• Maximal pain intensity assessed by Numeric Rating Scale (NRS) at rest and during movement
• Proportion of patients experiencing severe pain (NRS > 6)
• Duration of post-anesthesia care unit (PACU) stay
• Time to hospital discharge
• Incidence of side effects and adverse effects
• Proportion of participants with postoperative complications greater than grade 1 according to Clavien-Dindo classification up to POD 30
• Hospital readmission rates up to POD 30
• Patient satisfaction and experience

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population included both **male and female subjects** aged **18 years and older**, representing an adult population. Participants were classified as **ASA class I-III**, indicating a range from healthy individuals to those with severe systemic disease that is not incapacitating. The trial specifically recruited patients scheduled for elective **laparoscopic bariatric surgery** or **laparoscopic cholecystectomies** under **general anesthesia**. Women of childbearing capacity were required to have a negative pregnancy test or be using highly effective contraception methods. Written informed consent was obtained from all participants prior to enrollment. The trial focused on individuals undergoing these specific surgical procedures to evaluate outcomes related to **post-operative nausea and vomiting**.

This is a prospective, **double-blind**, **randomized**, **controlled** clinical trial designed to evaluate the impact of long-acting **NK1-** and **5-HT3 receptor antagonists** on postoperative recovery when used as **prophylaxis** for **post-operative nausea and vomiting** in patients undergoing **laparoscopic surgery**. The trial is classified as a **phase III** study and involves the administration of investigational medicinal products including **palonosetron** at a maximum daily dose of 75 µg administered via **intravenous bolus**, **fosaprepitant** at a maximum daily dose of 150 mg administered via intravenous bolus, **ondansetron** at a maximum daily dose of 4 mg administered via intravenous bolus as a **comparator**, and **sodium chloride** solution for infusion at a maximum daily dose of 500 ml administered intravenously as a **placebo**. The maximum treatment period for all investigational products is one day.

The primary objective of the trial is to determine whether the reduction in QoR-15swe scores from baseline before surgery to the first postoperative day is at least 8.0 points smaller in the intervention group compared to the control group. The **primary endpoint** is the QoR-15swe score measured preoperatively at baseline and on postoperative day 1. **Secondary endpoints** include QoR-15swe scores on postoperative days 0, 2, and 3, events of **nausea** or **vomiting** at the post-anesthesia care unit, during hospital stay, and at home up to postoperative day 3, use of **antiemetics** at the post-anesthesia care unit, during hospital stay, and at home up to postoperative day 3, pain assessments using the **numeric rating scale** at the post-anesthesia care unit, during hospital stay, and at home up to postoperative day 3, time spent at the post-anesthesia care unit, time at hospital until discharge, events of known side effects of investigational medicinal products such as infusion-site reactions, **headache**, visual disturbances, **constipation**, **diarrhoea**, and tiredness, complications from postoperative day 0 to postoperative day 30 according to the **Clavien-Dindo classification**, and themes from qualitative interviews of patient experiences on postoperative recovery using inductive thematic analysis conducted 30 to 90 days after the first visit.

Eligible participants include adult male or female subjects aged 18 years or older with **ASA class** I to III who are scheduled for elective laparoscopic bariatric surgery or laparoscopic cholecystectomies under **general anesthesia**. Principal inclusion criteria require that subjects have provided written informed consent to participate in the trial. Women of childbearing capacity are eligible only if a pregnancy test is negative or if they are using highly effective contraception methods. The trial is expected to commence recruitment on April 1, 2026, with an estimated end date of June 30, 2028.

Participant involvement begins with a screening visit to assess eligibility and obtain informed consent. Following enrollment, subjects undergo the scheduled surgical procedure during which the investigational medicinal products are administered according to the randomization protocol. Postoperative assessments are conducted at multiple time points including immediately after surgery in the post-anesthesia care unit, during the hospital stay, and at home through postoperative day 3. Follow-up visits or assessments continue up to postoperative day 30 to monitor for complications. A subset of participants may be invited to participate in qualitative interviews between 30 and 90 days after the first visit to provide insights into their postoperative recovery experiences. The expected length of participant involvement from enrollment to the final follow-up assessment is approximately 30 to 90 days. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events requiring discontinuation of investigational medicinal products, protocol violations, or other safety concerns as determined by the investigator.

The experimental treatment regimen consists of two active antiemetic agents administered in combination. **Palonosetron**, a long-acting **5-HT3 receptor antagonist**, is provided as a **solution for injection** in a pharmaceutical form suitable for parenteral administration. The maximum daily dose is **75 micrograms**, which also represents the maximum total dose per treatment period. Palonosetron is administered via **intravenous bolus** route. The treatment period is limited to **1 day**, reflecting its use as prophylaxis for **postoperative nausea and vomiting**.

**Fosaprepitant**, a long-acting **NK1 receptor antagonist**, is administered as part of the experimental intervention. This agent is supplied as a **solution for infusion** and is given at a maximum daily dose of **150 milligrams**, which constitutes the maximum total dose for the treatment period. Fosaprepitant is administered via **intravenous bolus** route. Similar to palonosetron, the maximum treatment period is **1 day**. Both experimental medications are classified as antiemetics and are intended to provide prophylactic coverage against postoperative nausea and vomiting in patients undergoing **laparoscopic surgery**.

The comparator treatment consists of **ondansetron**, a standard antiemetic agent used in clinical practice. Ondansetron is provided as a **solution for injection** and is administered at a maximum daily dose of **4 milligrams**, which represents the maximum total dose for the treatment period. The route of administration is **intravenous bolus**, and the treatment duration is **1 day**. Ondansetron serves as the active comparator to evaluate the efficacy of the experimental combination therapy.

**Sodium chloride** solution is utilized as a **placebo** in this double-blind, randomized trial. It is supplied as a **solution for infusion** with a maximum daily volume of **500 milliliters**, which also represents the maximum total volume administered during the treatment period. Sodium chloride is administered via the **intravenous** route over a treatment period of **1 day**. The use of sodium chloride solution as placebo allows for appropriate blinding and control in the study design, ensuring that the evaluation of the experimental intervention is conducted under rigorous scientific conditions.

Efficacy will be assessed using the QoR-15swe (Quality of Recovery-15 Swedish version) as the primary endpoint. The primary efficacy parameter evaluates whether the reduction in QoR-15swe scores from baseline before surgery to the first postoperative day (POD 1) is at least 8.0 points smaller in the intervention group compared to the control group. QoR-15swe scores will be measured preoperatively at baseline and on POD 1.

Secondary efficacy assessments include QoR-15swe measurements on POD 0, POD 2, and POD 3. Additional secondary endpoints comprise events of nausea or vomiting at the post-anesthesia care unit (PACU), during hospital stay, and at home up to POD 3. Use of antiemetics will be monitored at PACU, at the hospital, and at home up to POD 3. Pain assessments using the Numerical Rating Scale (NRS) will be conducted at PACU, during hospital stay, and at home up to POD 3. Time spent at PACU and time at hospital until discharge will be recorded. Events of known side effects of the investigational medicinal product, including infusion-site reactions, headache, visual disturbances, constipation, diarrhoea, and tiredness, will be evaluated. Complications from POD 0 to POD 30 will be assessed according to the Clavien-Dindo classification. Qualitative interviews of patient experiences on postoperative recovery will be conducted 30 to 90 days after the first visit, with data analyzed using inductive thematic analysis.