Analgesic Efficacy of Intravenous Acetaminophen After Video-assisted Thoracic Surgery

A Double-blind, Randomized, Placebo-controlled Study to Compare the Effectiveness of IV Acetaminophen Administered Intra-operatively in Reducing the Use of Opiates to Treat Post-operative Pain

We will study the efficacy of FDA approved intravenous (IV) acetaminophen ("Ofirmev", © 2011 Cadence Pharmaceuticals, Inc.) in reducing opioid consumption after minimally invasive thoracic surgery in a double blind randomized trial. This drug has been shown in Europe to reduce the need for patient controlled analgesia and the total dose of opioids, which have serious side effects in thoracic surgery patients. We will compare the use of IV patient-controlled morphine (PCA) in two groups of subjects in treating postoperative pain. We will determine if IV acetaminophen reduces post-operative morphine requirements (primary end point). We will also assess subject pain scores and post-operative complications associated with pain management as secondary end points. Our hypothesis is that the study arm receiving intravenous acetaminophen will have lower total morphine consumptions compared to the placebo group.

Study Overview

• Status: Completed
• Conditions: Lung Tumor
• Intervention / Treatment: Drug: Saline Placebo; Drug: IV Acetaminophen

Detailed Description

We will study the efficacy of FDA approved intravenous (IV) acetaminophen ("Ofirmev", © 2011 Cadence Pharmaceuticals, Inc.) in reducing opioid consumption after minimally invasive thoracic surgery in a double blind randomized trial. This drug has been shown in Europe to reduce the need for patient controlled analgesia and the total dose of opioids, which have serious side effects in thoracic surgery patients. We will compare the use of IV patient-controlled morphine (PCA) in two groups of subjects in treating postoperative pain. One group of subjects will receive IV acetaminophen every six hours beginning within 30 minutes before surgical end time and continuing for 24 hours plus IV morphine PCA, and the other group will receive IV placebo every six hours plus IV morphine PCA, a standard treatment for postoperative pain. We will determine if IV acetaminophen reduces post-operative morphine requirements (primary end point). We will also assess subject pain scores and post-operative complications associated with pain management as secondary end points. Our hypothesis is that the study arm receiving intravenous acetaminophen will have lower total morphine consumptions compared to the placebo group.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Any elective VATS patients with low probability of conversion to thoracotomy as determined by surgery.
• Ages 18-99
• American Society of Anesthesiologists Physical Status I-III, hemodynamically stable
• Male or female

Exclusion Criteria:

• Age less than 18.
• Patient refusal
• High probability of conversion to thoracotomy as determined by surgeon
• Conversion of procedure to thoracotomy (subjects will be withdrawn if VATS procedure is converted to thoracotomy, as thoracotomy is more invasive and will likely require additional analgesia such as neuraxial and regional anesthesia).
• Scheduled procedure of VATS Pleurodesis/decortication
• History of Interstitial Lung Disease
• Emergency case
• Known allergy/adverse reaction to acetaminophen, morphine, or fentanyl
• History of drug or alcohol abuse
• Patients on preoperative analgesic therapy within one week of surgery
• Contraindication to self administered morphine (unable to understand PCA)
• Need for postoperative mechanical ventilation
• Necessary major deviation for intraoperative study protocol as per the discretion of the intraoperative attending anesthesiologist
• History of congestive heart failure, renal failure, liver failure
• Pregnant or breastfeeding women
• Weight less than 51 kg

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline Placebo; Subjects will receive a saline placebo infusion administered over 15 minutes every 6 hours for 24 hours.	Drug: Saline Placebo; Normal saline placebo given every six hours for a total of four doses if randomized to the placebo arm.; Other Names: Normal saline solution
Active Comparator: IV Acetaminophen; Subjects will receive an infusion of 1 g of intravenous acetaminophen administered over 15 minutes every 6 hours for 24 hours with a maximum dose of 4 grams.	Drug: IV Acetaminophen; 1000mg IV Ofirmev given every six hours for a total of four doses.; Other Names: Paracetamol; Ofirmev

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Morphine Consumption (mg)	How much morphine the subject consumes in the first 24 hours after surgery (mg).	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of PCA Requests in First 24 Hours Post-Operation	The total number of Patient Controlled Analgesic (PCA) requests in the first 24 hours after the conclusion of the subject's operation	24 hours post-operation
VAS Pain Score 2 Hours Post Operation	2 hours after the conclusion of their operation,participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled "No Pain" (score of 0) and "Worst possible pain" (score of 100).	2 Hours Post Operation
VAS Pain Score 6 Hours Post-Operation	6 hours after the conclusion of their operation, participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled "No Pain" (score of 0) and "Worst possible pain" (score of 100).	6 Hours Post-Operation
VAS Score 24 Hours Post-Operation	24 Hours after the conclusion of the subject's operation, participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled "No Pain" (score of 0) and "Worst possible pain" (score of 100).	24 hours post-operation

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Hugh Hemmings, MD, PhD, Weill Medical College of Cornell University

Publications and helpful links

Helpful Links

• Label information for acetaminophen (ofirmev)

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: January 31, 2013
• First Submitted That Met QC Criteria: January 31, 2013
• First Posted (Estimate): February 4, 2013

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: acetaminophen; thoracic surgery; VATS; lung surgery; intravenous acetaminophen; thoracoscopic; ofirmev
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 1204012295

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD