Dual-dose Aprepitant to Reduce Postoperative Nausea and Vomiting After Laparoscopic Bariatric Surgery. (DDA-PONV)

Dual-dose Aprepitant to Reduce Postoperative Nausea and Vomiting After Laparoscopic Bariatric Surgery: a Prospective, Randomised, Placebo-controlled, Triple-blind, Single Centre Trial.

Postoperative nausea and vomiting (PONV) is unpleasant and increases health care costs. Despite modern techniques and prophylaxis, PONV rates remain high after laparoscopic bariatric surgery. We aim to reduce PONV after laparoscopic bariatric surgery using aprepitant with a similar scheme used for emetogenic chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Postoperative Nausea and Vomiting; Bariatric Surgery
• Intervention / Treatment: Drug: Aprepitant 80 mg; Drug: Placebo

Detailed Description

Postoperative nausea and vomiting (PONV) is not only a disturbing and unpleasant experience for the patient, it also increases length of post anaesthesia care unit (PACU) and hospital stay. In addition, PONV increases the risk for unplanned admission, risk for complications and in the end, health care costs. Risk factors have been identified more than 20 years ago by Apfel et. al., whose screening score has been widely implemented to augment perioperative prophylaxis. But despite modern anaesthetic techniques and combined antiemetic prophylaxis, PONV rates remain high in patients at high risk for PONV: in a recent retrospective study in female patients after laparoscopic bariatric surgery, up to 68% suffered from PONV during the first 48 hours after surgery despite triple antiemetic prophylaxis. While aprepitant is prescribed for three consecutive days after chemotherapy, there is no study so far evaluating the effect of a second dose of aprepitant 24 hours after surgery to prevent the increase in PONV after PACU discharge. We hypothesise, that adding two scheduled doses of aprepitant (2 hours before and 24 hours after surgery) to a twofold antiemetic regimen will significantly reduce cumulative PONV in the first 48 hours after laparoscopic bariatric surgery in patients with moderate to high risk for PONV.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 18 and more
• Scheduled for an elective, laparoscopic bariatric surgery (either laparoscopic gastric sleeve resection or laparoscopic gastric bypass)
• BMI > 30 kg/m2
• moderate to high risk for PONV (defined as APFEL score of 2 or higher)
• Informed Consent as documented by signature (see appendix 2).

Exclusion Criteria:

• emergency or open abdominal surgery;

• contraindication to aprepitant:

  • known allergy/hypersensitivity
  • on pimozide, terfenadine, astemizole or cisapride

• on regular medication with known interaction with the study drug:

  • benzodiazepines
  • ketoconazole, itraconazole
  • rifampicin, clarithromycin
  • paroxetine
  • diltiazem
  • carbamazepine, phenytoin
  • tolbutamid
  • ritonavir
  • St. John's wort
• patients with history of chronic nausea/vomiting or taking medication with known antiemetic properties (dexamethasone, metoclopramide, meclozine)
• severe hepatic impairment (Child-Pugh score >9);
• chronic substance abuse (except smoking);
• significant psychiatric disease precluding interrogation;
• Inability to follow the procedures of the study, e. g. due to language barrier;
• Women who are pregnant or breast feeding;
• Intention to become pregnant during the course of the study and 2 months after surgery;
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a condom in addition to a medically reliable method of contraception for the entire study duration and 2 months after surgery, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.
• male participants need to use a condom for the whole study period and 2 months after surgery;
• unable to consent, e. g. patients incapable of judgment needing next-of-kin consent or under tutelage;
• participation in another study with an investigational drug within the 30 days preceding and during the present study;
• previous enrolment into the current study;
• enrolment of the investigator, his/her family members, employees and other dependent persons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum; Patients will receive 2 encapsulated capsules containing aprepitant 80mg to be ingested with a sip of water 2 hours before surgery and 24 hours after surgery. Surgery will follow our hospital enhanced recovery after surgery (ERAS) standard (general anaesthesia using volatile anaesthetics, intravenous dexamethasone 8mg and ondansetron 4mg for PONV prophylaxis).	Drug: Aprepitant 80 mg; Encapsulated capsule of aprepitant 80mg to make it look alike to the placebo.; Other Names: Aprepitant Zentiva 80mg
Placebo Comparator: Placebo; Patients will receive similar looking encapsulated capsules containing only placebo to be ingested with a sip of water 2 hours before surgery and 24 hours after surgery. Surgical and anaesthetic procedures are identical to the verum arm.	Drug: Placebo; Encapsulated placebo capsules for optical, acoustical and haptic blinding.; Other Names: Placebo Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative rate of PONV 48 hours after surgery	Primary outcome is cumulative rate of PONV (defined as emesis including vomiting and retching, severe nausea [>6/10 on a numeric rating scale (NRS)] and use of rescue medication) at 48 hours after surgery.	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of nausea	mild [NRS 1-3], moderate [NRS 4-6] and severe [NRS 7-10]	3, 24 and 48 hours after surgery
Incidence of emesis	number	3, 24 and 48 hours after surgery
Use of rescue medication for PONV	medication, cumulative dose, route	3, 24 and 48 hours after surgery
Use of opioid analgesics	mg of oral morphine equivalents	3, 24 and 48 hours after surgery
Use of non-opioid analgesics	medication, cumulative dose, route	3, 24 and 48 hours after surgery
Use of co-analgesics	medication, cumulative dose, route	3, 24 and 48 hours after surgery
Rate of delayed PACU discharge because of PONV	number	24 hours after surgery
Length of PACU stay	hours	24 hours after surgery
Length of hospital stay	hours	48 hours after surgery
Surgical complications at 30 days after surgery	using Clavien-Dindo classification (number and grade)	30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	pre-defined events, safety outcome	3, 24 and 48 hours after surgery, 30 days after surgery

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Christian M Beilstein, MD, Bern University Hospital, University of Bern, Bern, Switzerland

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2022
• Primary Completion (Actual): February 20, 2025
• Study Completion (Actual): February 20, 2025

Study Registration Dates

• First Submitted: December 28, 2021
• First Submitted That Met QC Criteria: December 30, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Postoperative Complications; Pathologic Processes; Signs and Symptoms, Digestive; Nausea; Vomiting; Postoperative Nausea and Vomiting; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neurotransmitter Agents; Neurokinin-1 Receptor Antagonists; Aprepitant; Fosaprepitant
• Other Study ID Numbers: BECD-2-21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No