Effects of Intravenous Acetaminophen in Patients Undergoing Thoracoscopic Surgery (IVTylenol)

This is a single-center, randomized, double-blind, placebo-controlled trial. A total of 100 patients, 50 per treatment arm, undergoing minimally invasive thoracic surgery will be randomized 1:1 across 2 treatment arms: Ofiramev® (acetaminophen) injection 1,000 mg (100 mL) plus patient-controlled analgesia (PCA) and 100 mL placebo plus PCA.

Study Overview

• Status: Withdrawn
• Conditions: Post-thoracotomy Pain Syndrome
• Intervention / Treatment: Drug: Ofiramev® (IV Acetaminophen); Drug: Placebo IV administration

Detailed Description

This is a single-center, randomized, double-blind, placebo-controlled trial. A total of 100 patients, 50 patient per treatment arm, undergoing minimally invasive thoracic surgery will be randomized 1:1 across 2 treatment arms: Ofiramev® (acetaminophen) injection 1,000 mg (100 mL) plus patient-controlled analgesia (PCA) and 100 mL placebo plus PCA. All patients will be enrolled from a single site.50 patient will be enrolled in each arm (placebo/ acetamophin). Each subject will be administered a single dose of study drug or placebo infused over 15-minutes, four times, six hours apart. The duration of subject participation will be ten weeks. Total duration of the study is expected to be 52 weeks. The primary endpoints of the study will be the amount of postoperative narcotic used, patient assessment of pain as measured by a validated pain survey, and length of stay in the hospital.

For postoperative pain assessment, the Numeric Rating Scale (NRS) will be used (NRS: 0-10; 0: no pain, 10: worst pain imaginable). Pain will be evaluated at 2-hour intervals in the post-anesthesia care unit followed by 4-hour intervals once the patient is transferred to the floor. Nurses who are blinded to the analgesic method will evaluate pain levels. Hospital length of stay will be measured from date of admission to date of discharge.

The study drug, Ofiramev® (acetaminophen) injection is a non-salicylate antipyretic and non-opioid analgesic agent. The precise mechanism of the analgesic and antipyretic properties of acetaminophen is not established but is thought to primarily involve central actions. The study drug is a clear, colorless formulation of acetaminophen intended for intravenous infusion and is packaged in glass vials containing 100 mL of 1000 mg acetaminophen (10 mg/mL). The investigational pharmacy will transfer the study drug to a 100 mL bag. The placebo solution will consist of 100 mL normal saline in an identical 100 mL bag with identical labeling. Prior to the induction of anesthesia subjects will receive a single dose of Ofiramev® or placebo by IV infusion over 15 minutes. Following the first dose, each subsequent dose will be given every 6 hours for a total of 4 doses. Regardless of treatment arm, study drug and placebo will be dispensed in the same manner.

Investigational drugs are stored in the investigational drug service storeroom and/or pharmacy satellite depending on the nature of the drug study. All study drug inventory is labeled with IRB identification and stored separately from other commercial drug products under appropriate security and stability conditions. OFIRMEV should be stored at 20°C to 25°C (68°F to 77°F) and should be used within 6 hours after opening.

An accurate and current accounting of the dispensing and return of study drug for each subject will be maintained on an ongoing basis by a member of the study site staff. The number of study drug dispensed and returned by the subject will be recorded on the Investigational Drug Accountability Record. The study monitor will verify these documents throughout the course of the study.

Patients can voluntarily withdraw from the trial for any reason at any time. Subjects will be withdrawn from the study in the event of unplanned conversion to open thoracic surgery or administration of neuraxial opioids. If a subject is withdrawn from treatment due to an adverse event, the subject will be followed and treated by the Investigator until the abnormal parameter or symptom has resolved or stabilized.

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-99 years
• Undergo minimally invasive thoracic surgery at UTMB
• Weight > 50 kg
• Written informed consent obtained from subject

Exclusion Criteria:

• Hepatic dysfunction
• Renal dysfunction
• Chronic alcohol consumption
• Acetaminophen sensitivity
• Opioid tolerance
• History of chronic pain
• Vulnerable populations including pregnant and prisoners
• Extension into an extrathoracic compartment (i.e. minimally invasive esophagectomy), or concomitant chest wall resection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ofiramev®( IV Acetaminophen); Patients randomized to the treatment arm will receive 1 g (100 mL) intravenous acetaminophen infused over 15-minutes every 6 hours for 4 doses total.	Drug: Ofiramev® (IV Acetaminophen); Post -op pain medication; Other Names: IV Tylenol
Placebo Comparator: Placebo IV administration; Patients randomized to the placebo arm will receive 100 mL of normal saline infused over 15 minutes every 6 hours for 4 doses total	Drug: Placebo IV administration; Post -op pain; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of postoperative narcotic used.	the amount of postoperative narcotic used, after surgery.	Within 7 days of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The amount of postoperative pain.	The amount of postoperative patient assessment of pain as measured by a validated pain survey (NRS)	An average of 4 days
length of stay in the hospital	length of stay in the hospital from admission to discharge of patient after surgery.	An average of 4 days
The amount of postoperative pain.	The amount of postoperative patient assessment of pain as measured by patient satisfaction survey on 2-4 weeks post-op clinic follow-up.	Within 2-4 weeks of surgery

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: Mallinckrodt
• Investigators: Principal Investigator: Ikenna Okereke, MD, University Of Texas Medical Branch At Galveston

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2018
• Primary Completion (Anticipated): June 1, 2019
• Study Completion (Anticipated): June 1, 2019

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: February 9, 2017
• First Posted (Actual): February 14, 2017

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: February 1, 2019
• Last Verified: December 1, 2017

More Information

Terms related to this study

• 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: 16-0340

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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