Prospective, Double Blind, Placebo Control, Bariatric IV Ace

NCT ID: NCT02452320

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-01-31

Brief Summary

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.

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Randomized

Subjects randomized into the active treatment group will receive intravenous acetaminophen

Group Type: ACTIVE_COMPARATOR

intravenous acetaminophen

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Ofirmev; Normal Saline

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter A Goldstein, MD

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medical College

New York, New York, United States

Countries

United States

Other Identifiers

1503016056

Identifier Type: -

Identifier Source: org_study_id