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Intraoperative and Post-operative Analgesic Effect of IV Acetaminophen for Sinus Surgery (IVAPAP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01608308
Recruitment Status : Completed
First Posted : May 31, 2012
Results First Posted : September 4, 2015
Last Update Posted : October 16, 2015
Sponsor:
Collaborator:
Mallinckrodt
Information provided by (Responsible Party):
Davide Cattano, The University of Texas Health Science Center, Houston

Tracking Information
First Submitted Date  ICMJE May 25, 2012
First Posted Date  ICMJE May 31, 2012
Results First Submitted Date  ICMJE June 12, 2015
Results First Posted Date  ICMJE September 4, 2015
Last Update Posted Date October 16, 2015
Study Start Date  ICMJE July 2012
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 5, 2015)
Pain Level Assessed Using a Visual Analogue Scale (VAS) Scale [ Time Frame: 15 minutes and 120 minutes Post-Operatively ]
VAS is a validated, self-reported data sheet assessing average pain intensity. Possible scores range from 0 (no pain) to 10 (highest level of pain).
Original Primary Outcome Measures  ICMJE
 (submitted: May 29, 2012)
Assess the efficacy of IV acetaminophen in controlling postoperative pain [ Time Frame: 4 Hours Post-Operatively ]
Pain will be assessed using a VAS Scale at regular time intervals post-operatively.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 25, 2015)
  • Total Doses of Postoperative Opiate (Morphine) Use [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    The total amount of morphine utilized in Postoperative Acute Care Unit (PACU) will be recorded. One dose is a 1mg bolus of morphine.
  • Number of Participants Who Received Intraoperative Supplemental Fentanyl [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Number of participants who received intraoperative supplemental fentanyl. The decision to administer fentanyl is based on hemodynamic changes, such as increasing blood pressure and heart rate.
  • Number of Participants Who Experienced Postoperative Morbidity (Nausea) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Post-operative nausea will be monitored and measured through direct observation and nursing clinical record
  • Postoperative Vital Sign (Systolic Blood Pressure) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.
  • Postoperative Vital Sign (Diastolic Blood Pressure) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.
  • Postoperative Vital Sign (Pulse) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.
  • Postoperative Vital Sign (Temperature) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.
  • Postoperative Vital Sign (Respiratory Rate) [ Time Frame: During Postoperative Acute Care Unit (PACU) stay (up to 4 hours after surgery) ]
    Postoperative vital signs (systolic and diastolic blood pressure, pulse, temperature, and respiratory rate) were measured at different time points up to 4 hours after surgery.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2012)
  • Investigate the effect of IV acetaminophen on the use of postoperative opioid analgesics [ Time Frame: During PACU Stay (Approximately 4 hours) ]
    The total amount of postoperative opioid use will be recorded as follows: after the patient has arrived in the PACU (post anesthesia care unit), the incidence and intensity of pain will be assessed using a VAS (0-100) as described above. Pain relief will be achieved by incremental doses of morphine 1 mg bolus, based on a VAS score of 40 and above, to be repeated every 5 minutes if needed. The total amount of morphine utilized in PACU will be recorded.
  • Analyze effects of IV acetaminophen on intraoperative analgesic use [ Time Frame: Duration of Surgery (Approximately 3-4 Hours) ]
    Brief episodes of tachycardia and hypertension are expected in FESS procedures. These will be treated by increasing inhalational agents of 0.5% inspired fraction at a time. A supplemental dose of fentanyl in the amount of 1 mcg/kg will be available for HR and BP greater than 15-20% above baseline after no response to volatile change. The following measurements will be recorded: total amount of fentanyl utilized; the hemodynamic parameters during surgery and anesthesia; the inspired fraction of inhalational agent; and the number of step-wise increases for hemodynamic control.
  • Identify potential correlation between vital signs and postoperative pain intensity [ Time Frame: Duration of PACU Stay (Approximately 4 Hours Post-Operatively) ]
    The association of postoperative pain intensity with vital sign changes (including heart rate, respiratory rate, blood pressure, and temperature) will be assessed. Each patient's vital signs will be collected at the specified time points, in addition to measuring pain intensity using the VAS scale. Data will be collected and analyzed to search for a statistical correlation between postoperative pain intensity and vital sign changes.
  • Examine the effect of IV acetaminophen on post-operative quality of recovery [ Time Frame: Upto 48 Hours Post-Operatively ]
    Adverse events including, dizziness, nausea/vomiting, tachy/brady-cardia, arrhythmia, hypertension, hypotension, allergic reaction, etc. will be monitored. A questionnaire evaluating quality and efficacy of pain management will be given to the patient before discharge. A telephone interview will be administered within 48 hours from discharge to assess for pain control, utilization of analgesics, and patient satisfaction
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intraoperative and Post-operative Analgesic Effect of IV Acetaminophen for Sinus Surgery
Official Title  ICMJE A Double Blind, Randomized, Placebo-controlled Study to Investigate the Effectiveness of IV Acetominophen Administered During Functional Endoscopic Sinus Surgery in Reducing the Use of Opiates to Treat Postoperative Pain
Brief Summary The purpose of this study is to assess the use of IV acetaminophen (Ofirmev) as a and safe and efficacious agent in reducing post-operative pain; we hypothesize that its use will reduce post-operative pain when compared to a control group using the visual analogue score (VAS) analog pain scoring system.
Detailed Description

Unrelieved postoperative pain may result not only in suffering and discomfort, but may also lead to multiple physiological and psychological consequences which can contribute to adverse perioperative outcomes. Inadequate perioperative analgesia can potentially contribute to a higher incidence of myocardial ischemia. Additionally, the use of opioids has been associated with major side effects that can include impaired wound healing and delayed gastrointestinal (GI) motility that results in prolonged postoperative ileus.

Intravenous acetyl-para-aminophenol (APAP, also known as acetaminophen) is considered as the non-opioid analgesic of choice to treat postoperative mild and moderate pain, and has been demonstrated in several randomized trials to be both safe and effective at reducing acute post-operative pain in both children and adults. Furthermore, in the treatment of severe pain, it can reduce the need for opioid-analgesics while exhibiting a relatively limited side effect profile when compared to opioids and nonsteroidal anti-inflammatory drugs.

Chronic rhinosinusitis (CRS) describes a group of disorders characterized by inflammation of the nasal mucosa and/or paranasal sinuses for at least 12 consecutive weeks. In the United States, CRS affects approximately 30 million people, and represents 2% of the primary diagnoses in physician office visits, resulting in an estimated 200,000 sinus procedures annually. Patients suffering from CRS that is refractory to medical management complain of symptoms that include fatigue, headache, nasal drainage, facial pain and pressure, and decreased sense of smell. Functional endoscopic sinus surgery (FESS) represents a surgical approach to treating CRS that is unresponsive to medical management. Outcomes studies have identified FESS as efficacious at reducing the majority of symptoms related to CRS. Despite this, pain associated with CRS remains a significant co-morbidity that often is resistant to both medical and surgical management. Reducing the incidence and severity of acute post-operative pain is paramount to reducing the development of chronic pain that may exacerbate a patient's existing pain. The use of pre- and intra- operative IV acetaminophen thus serves as a unique pain management modality in this setting, as it has the potential for reducing post-operative complications and pain, with the additional benefit of minimal intraoperative bleeding, an undesirable complication often associated with FESS and with the use of non-steroidal anti-inflammatory drugs (NSAIDs).

The use of IV acetaminophen in ear, nose, and throat (ENT) surgery is not a novel endeavor. Indeed, studies have demonstrated the efficacy and safety of IV acetaminophen for use in tonsillectomy and FESS. We wish to provide a more comprehensive analysis of pain management in the setting of FESS in the following ways :

  1. by administering IV acetaminophen perioperatively (before start of surgery, and after surgery completion;
  2. by employing a pain score of 4 (whereas other studies use 3) as a cutoff for breakthrough pain; and,
  3. by addressing novel outcomes including patient sedation and patient satisfaction, in addition to opioid analgesic use.

In our institution, we have completed a preliminary pilot study exploring the use of intravenous anesthesia which included acetaminophen during bilateral endoscopic sinus surgery. Secondary outcomes measured during the study included:

  1. Pain
  2. Rescue analgesic use
  3. Nausea/Vomiting
  4. Time spent in recovery
  5. Successful discharge from the PACU and the Hospital

Our pilot data has reaffirmed that the procedure is overall benign, with few associated risks and adverse events. Of note, none of the patients in our preliminary study required admission to the hospital after surgery for further observation as a result of uncontrolled pain or nausea. Based on this experience, we would like to explore the efficacy of intravenous acetaminophen (Ofirmev), a non opioid/non steroidal analgesic, in endoscopic sinus surgery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Chronic Sinusitis
Intervention  ICMJE
  • Drug: IV Acetaminophen
    1000mg IV acetaminophen over 15 minutes every 4 hours for up to 2 doses.
    Other Name: OFIRMEV (Cadence Pharamceutical, San Diego, USA)
  • Drug: Placebo
    100 mL of 0.9% normal saline over 15 minutes in place of IV acetaminophen.
    Other Name: Normal Saline
Study Arms  ICMJE
  • Experimental: IV Acetaminophen
    The experimental group will receive a preoperative dose of 1000mg IV acetaminophen over 15 minutes. This will occur at least 15 minutes before the start of surgery. Another 1000mg dose of IV acetaminophen will be administered 4 hours after the first dose. A rescue analgesic containing oxycodone will also be provided (with APAP concentrations of 325 mg per Hospital and FDA recommendations).
    Intervention: Drug: IV Acetaminophen
  • Placebo Comparator: Control
    The control group (Placebo) will receive 100 mL of 0.9% normal saline in place of IV acetaminophen in the same manner as the experimental group; the investigator/physician in question will be blinded to the agent that is being administered. Patients will be discharged with instruction to continue APAP 500 mg PO every 6-8 hours. A rescue analgesic containing oxycodone will also be provided (with APAP concentrations of 325 mg per Hospital and FDA recommendations).
    Intervention: Drug: Placebo
Publications * Tyler MA, Lam K, Ashoori F, Cai C, Kain JJ, Fakhri S, Citardi MJ, Cattano D, Luong A. Analgesic Effects of Intravenous Acetaminophen vs Placebo for Endoscopic Sinus Surgery and Postoperative Pain: A Randomized Clinical Trial. JAMA Otolaryngol Head Neck Surg. 2017 Aug 1;143(8):788-794. doi: 10.1001/jamaoto.2017.0238.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 5, 2015)
62
Original Estimated Enrollment  ICMJE
 (submitted: May 29, 2012)
60
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. Patients undergoing surgical management for CRS (with or without polyps)
  2. Operating time must be at least 2 hours in duration.
  3. Number of sinuses involved must be 3 or greater

Exclusion criteria:

  1. History of hypersensitivity to acetaminophen
  2. End stage renal disease
  3. End stage liver disease
  4. History of chronic pain, or use of opioid medication in the previous two weeks
  5. Severe depression or anxiety
  6. Use of gabapentin or any other pain modulator
  7. History of acute sinusitis or mucocele
  8. History of seizures
  9. Known or suspected history of alcohol or drug abuse
  10. Known or suspected history of morphine intolerance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 68 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01608308
Other Study ID Numbers  ICMJE HSC-MS-12-0111
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Davide Cattano, The University of Texas Health Science Center, Houston
Study Sponsor  ICMJE The University of Texas Health Science Center, Houston
Collaborators  ICMJE Mallinckrodt
Investigators  ICMJE
Principal Investigator: Davide Cattano, MD, PhD The University of Texas Health Sciences Center at Houston
PRS Account The University of Texas Health Science Center, Houston
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP