Prospective, Double Blind, Placebo Control, Bariatric IV Ace (Bariatricace)

Prospective, Double Blind, Placebo Control, Study of Acetaminophen iv on Hospital Length of Stay in Morbidly Obese Individuals Undergoing Elective Laparoscopic Sleeve Gastrectomy

The purpose of this study is to determine if the administration of acetaminophen given intravenously (through an IV) beginning during surgery and then for 3 additional doses during the first 24 hours post-operatively will reduce the length of time subjects undergoing elective sleeve gastrectomy spend in the hospital following this operation. Additional questions that may be answered include whether administration of the study medication leads to improvement in pain control, a reduction in post-operative nausea and vomiting, and an overall improvement in quality of recovery.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Placebo; Drug: intravenous acetaminophen

Detailed Description

Morbid obesity is defined as a body mass index (BMI: weight [kg] / height [m]2) ≥ 40 or ≥ 35 if associated with comorbidities, and it is widely prevalent, nationally and globally. Overweight or obese individuals have increased morbidity and mortality. Among the many available treatment options, surgical management of obesity has been shown to be the most reliably effective in achieving sustained weight loss and improvements in glycemic, lipidemic, and blood pressure control, and improves five and ten year survival in contrast to matched controls who did not have surgery. Various surgical approaches have been used to provide long-term control of morbid obesity and its associated comorbidities, including laparoscopic sleeve gastrectomy.

During a sleeve gastrectomy the greater curvature of the stomach is separated from the lesser curvature and antrum, thereby eliminating ~85% of the total stomach, including the grehlin-producing portion of the stomach. A common complication of the procedure is postoperative nausea and vomiting (PONV), occurring in nearly 80% of patients undergoing the procedure. Risk factors for PONV include: female sex, history of PONV or motion sickness, nonsmoking, younger age, general vs. regional anesthesia, use of volatile anesthetics and nitrous oxide, administration of postoperative opioids, duration of anesthesia, and type of surgery (including cholecystectomy, laparoscopic, and gynecological). At the individual level, PONV adversely impacts both patient satisfaction and quality of life scores. At the systems level, PONV is associated with increased length of stay (LOS) in the post-anesthesia care unit and hospital, and can result in increased costs.

Both pharmacological and surgical approaches have been studied in an effort to reduce the incidence of PONV in sleeve gastrectomy patients. Omentopexy was unsuccessful, and pharmacologic prophylaxis with two [dexamethasone + odansetron; dexamethasone + granisetron; aprepitant + odansetron; or three (dexamethasone + odansetron + haloperidol; antiemetic agents was more effective than a single agent (odansetron or granisetron) alone in decreasing both nausea and vomiting. Even with triple therapy, just over 50% of patients were nauseous and 20% vomited within the first 36 hours following surgery, and hospital LOS was unaffected. Thus, there is a pressing need for improved control of PONV in sleeve gastrectomy patients.

Acetaminophen (N-(4-hydroxyphenyl)acetamide; paracetamol) is a mild analgesic whose main, but not sole, mechanism of action is thought to arise from inhibition of the cyclooxygenase pathway; the intravenous (iv) formulation (acetaminophen iv; ACP-iv) received US Food and Drug Administration (FDA) approval in November 2010 but has been available in Europe since 2002. It is approved by the FDA for the management of mild to moderate pain as a single agent and the management of moderate to severe pain with adjunctive opioid analgesics. Recently, two meta-analyses have evaluated the use of ACP-iv in the postoperative period for its efficacy in preventing postoperative pain [45] or reducing PONV [46]. In the study by De Oliveria et al., ACP-iv administration was found to significantly reduce postoperative pain, opioid consumption, and PONV. Similarly, the study by Apfel and colleagues indicated that iv-ACP, when administered prophylactically, reduced PONV as a consequence of improved pain control. With direct relevance to sleeve gastrectomy patients, a retrospective analysis of patients undergoing bariatric surgery (sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass) found that ACP-iv administration reduced opiate consumption and hospital LOS.

The investigators hypothesize that administration of ACP-iv in the perioperative period will reduce hospital LOS in sleeve gastrectomy subjects and will be associated with a reduction in hospital costs. The secondary hypothesis is that administration of ACP-iv will reduce PONV and improve subject satisfaction scores in the same subject population.

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• At least 18 years old
• BMI > 30
• Undergoing Elective Sleeve Gastrectomy
• Able to consent

Exclusion Criteria:

• Allergy/ Hypersensitive to acetaminophen or formulation incipients
• Allergy/Hypersensitive to aprepitant, ondasteron (serotonin type 3 receptor antagonists), dexamethasone
• Allergy to Propofol or formulation incipients (egg albumin, soy lecithin)
• Diagnosis or positive family history of malignant hyperthermia
• Abnormal LFTs (AST and ALT) >2x local upper limits of normal
• Renal impairment (creatinine clearance (CrCl) ≤ 30mL/min adjusted for obesity))
• Pregnancy
• Alcohol consumption > 3 drinks/day
• Requires awake intubation
• Unable to provide consent

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
Placebo Comparator: Control; Subjects randomized into the control group will not receive study medication, they will receive a placebo administered at the same schedule as the active drug in the other arm.	Drug: Placebo; Subjects randomized to placebo will receive every 6 hours for a total of 4 doses; first dose to be administered after induction of general anesthesia; Other Names: Normal Saline
Active Comparator: Randomized; Subjects randomized into the active treatment group will receive intravenous acetaminophen	Drug: intravenous acetaminophen; administration of 1000mg of intravenous acetaminophen or placebo every 6 hours for a total of 4 doses; first dose to be administered after induction of general anesthesia; Other Names: Ofirmev

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery-15 Patient Survey	Survey asking 15 questions with regard to how the patient is feeling scored on a scale from 0-10, with 0 being none of the time and 10 being all of the time. Possible scores range from 0-150, and scores with a higher value indicate a better outcome. Each subject was administered a baselineQoR-15 survey prior to surgery, and then one on postoperative days (POD) 1 and 2. If a subject was discharged prior to POD2, they were not given a QoR-15 survey that day.	Patients will be followed for the duration of hospital stay, expected average of 3 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Hospital Stay	Monitoring the length of hospital stay after undergoing surgery	Participants will be followed for the duration of hospital stay, expected average of 3 days.
Hospital Costs	Accessing billing codes/hospital costs for each enrolled subject from the time they are admitted until they are discharged from the hospital.	Costs incurred during hospital stay, expected average of 3 days.

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Peter A Goldstein, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2016
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 21, 2015
• First Posted (Estimate): May 22, 2015

Study Record Updates

• Last Update Posted (Actual): April 20, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: bariatric; Post-operative nausea and vomiting; laparoscopic Sleeve gastrectomy; intravenous acetaminophen
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 1503016056

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We will not be making IPD available