Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors

Randomized, Double-Blind, Placebo-Controlled Trial Comparing Opioid-Sparing and Opioid-Containing Analgesia Regimens Following Trans-sphenoidal Surgery for Pituitary Tumors

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02351700

Enrollment

Registered

2015-01-30

Start date

2015-02-01

Completion date

2016-04-01

Last updated

2021-10-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pain, Pituitary Tumor

Brief summary

A randomized, double-blind, placebo-controlled intervention trial involving 100 treated subjects undergoing endonasal trans-sphenoidal (ENTS) resection of pituitary lesion. Subjects will be randomized into two groups: 50 treated in the opioid-sparing arm and 50 treated in the standard post-operative medication arm.

Detailed description

Post-operative pain control is a common concern patients have when they consider undergoing a surgical procedure. Although effective for treating acute pain, opioid analgesics are also associated with dose-dependent adverse effects, including constipation, nausea and vomiting, altered mental status, and respiratory depression, all of which have been shown to increase patient length of stay. The use of non-opioid analgesics with different mechanisms of actions for acute pain control via a multi-modal approach is efficacious in reducing opioid consumption, decreasing the incidence of adverse effects, improving patient satisfaction and recovery time, and decreasing hospital costs.Certain minimally invasive procedures may afford many patients the opportunity to achieve adequate post-operative pain control with minimal to no requirement of opioid analgesics, thereby sparing the patient known adverse effects that can increase length of stay and costs. The ENTS approach for resection of pituitary tumors is the standard surgical procedure for these lesions, and is associated with pain that is more easily managed post-operatively, making it an ideal procedure for an opioid-sparing post-operative pain regimen. Anecdotally, the investigators note that in the investigator's post-operative pituitary patient population that post-operative pain can frequently be adequately managed with scheduled non-opioid analgesics, often without requiring breakthrough opioid doses. Another safe and effective non-opioid analgesic that is widely used in multi-modal pain management for moderate pain is IV Caldolor (ibuprofen). After literature review, the investigators were unable to find a study that had attempted to use an opioid-sparing analgesic regimen for post-operative pain control following ENTS approach for resection of pituitary tumors.

Interventions

DRUGIV Caldolor

IV Caldolor (IV ibuprofen) intraoperatively and postoperatively

DRUGIV Placebo

IV Placebo intraoperatively and postoperatively

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 79 Years

Healthy volunteers

Inclusion criteria

* Adult patient undergoing ENTS surgery for resection of pituitary tumor. * Adults \>18 years and \<80 years of age. * English speaking and literate or able to understand the use of a pain scale. * Body Mass Index \>19 and \<40 kg/m2

Exclusion criteria

* Renal failure (acute or chronic) or creatinine \>2.0 * Allergy or intolerance to acetaminophen, ibuprofen, or opioids * Pre-operative opioid tolerance, dependence, or abuse * Anaphylaxis to opioids * History of peptic ulcer disease or recent gastrointestinal bleed requiring surgery * Cirrhosis, hepatitis, liver transplant, or liver function studies out of normal range, defined as aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin\> 3x upper limit of normal range * Subject unwilling or unable to sign informed consent for the study * Pregnancy * Incarcerated patients

Design outcomes

Primary

Measure	Time frame	Description
Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour)	mean pain score over 48 hours	Comparison of pain scores between two arms using Visual Analog Scale (VAS) for Pain. Units of measure are 0=No Pain, 1=Annoying, 2=Mild Pain, 3=Troublesome, 4=Nagging Pain, Uncomfortable, 5=Distressing, 6=Miserable, 7=Horrible, 8=Intense, Dreadful, 9=Unbearable, 10=Worst Possible Pain. Higher values represent a worse outcome. There are no subscales.

Secondary

Measure	Time frame	Description
Breakthrough Narcotic Requirement	until discharge from hospital, an expected stay of 2 days	Rescue narcotic in both groups will be recorded and compared using a standard equianalgesic oral morphine equivalent (OME) calculation
Other Adverse Events	until discharge from hospital, an expected stay of 2 days	Epistaxis, potentially related to IV ibuprofen, will be compared between two groups

Other

Measure	Time frame	Description
Total Cost of Hospital Charges Compared Between Two Arms	until discharge from hospital, an expected stay of 2 days	Total hospital costs for patients in IV ibuprofen arm compared to IV placebo arm
Total Number of Doses of Any Anti-emetic Required Post-operatively in Both Groups	until discharge from hospital, an expected stay of 2 days	Use of antiemetics in first 48 hours after surgery
The Number of Participants Who Have a Bowel Movement During Hospitalization in Both Groups	until discharge from hospital, an expected stay of 2 days	patients with one or more bowel movement(s) in the first 48 hours after surgery
Length of Stay in Hospital Compared Between Two Arms	until discharge from hospital, an expected stay of 2 days	Length of hospital stay from time of surgery to time of discharge.

Countries

United States

Participant flow

Recruitment details

Adult patients undergoing endonasal transsphenoidal surgery for pituitary adenoma. Potential patients were identified in the Pituitary Clinic at Barrow Neurological Institute.

Pre-assignment details

Randomized 1:1 ratio with blinded treatment assignment. Used a computer-generated list from random.org.

Participants by arm

Arm	Count
Opioid-sparing Group Intravenous (IV) Caldolor (ibuprofen) (800mg every 8 hours) initiated during surgery and oral acetaminophen 1000mg every 6 hours initiated post-operatively and continued for the duration of the hospital stay (an expected average stay of 2 days) or 48 hours, whichever comes first. Breakthrough pain will be treated with rescue narcotics (IV morphine 2-4mg every 2 hours and oral oxycodone 5-15mg every 4 hours immediately post-operatively through discharge, an expected average stay of 2 days). Hydromorphone (IV 0.5-2mg every 2 hours and oral 2-4mg every 4 hours) will be used in patients with morphine or oxycodone allergy or intolerance. IV Caldolor (IV Ibuprofen): Compare addition of IV Caldolor (IV ibuprofen) intraoperatively and postoperatively against IV ibuprofen placebo added intraoperatively and postoperatively.	28
Standard Treatment Group IV Caldolor placebo will be initiated during surgery and oral acetaminophen 1000mg every 6 hours will be initiated post-operatively and continued for the duration of the hospital stay (an expected average stay of 2 days) or 48 hours, whichever comes first. Breakthrough pain will be treated with rescue narcotics (IV morphine 2-4mg every 2 hours and oral oxycodone 5-15mg every 4 hours immediately post-operatively through discharge, an expected average stay of 2 days). Hydromorphone (IV 0.5-2mg every 2 hours and oral 2-4mg every 4 hours) will be used in patients with morphine or oxycodone allergy or intolerance. IV Ibuprofen placebo: Compare addition of IV ibuprofen placebo intraoperatively and postoperatively against IV Caldolor (IV ibuprofen) added intraoperatively and postoperatively.	34
Total	62

Baseline characteristics

Characteristic	Opioid-sparing Group	Standard Treatment Group	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	14 Participants	5 Participants	19 Participants
Age, Categorical Between 18 and 65 years	14 Participants	29 Participants	43 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants	6 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants	28 Participants	55 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	28 Participants	30 Participants	58 Participants
Region of Enrollment United States	28 participants	34 participants	62 participants
Sex: Female, Male Female	13 Participants	18 Participants	31 Participants
Sex: Female, Male Male	15 Participants	16 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 28	0 / 34
other Total, other adverse events	2 / 28	0 / 34
serious Total, serious adverse events	0 / 28	2 / 34

Outcome results

Primary

Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour)

Comparison of pain scores between two arms using Visual Analog Scale (VAS) for Pain. Units of measure are 0=No Pain, 1=Annoying, 2=Mild Pain, 3=Troublesome, 4=Nagging Pain, Uncomfortable, 5=Distressing, 6=Miserable, 7=Horrible, 8=Intense, Dreadful, 9=Unbearable, 10=Worst Possible Pain. Higher values represent a worse outcome. There are no subscales.

Time frame: mean pain score over 48 hours

Population: All participants enrolled with the intent to treat.

Arm	Measure	Value (MEAN)	Dispersion
Opioid-sparing Group	Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour)	1.7 0-10 units on a scale	Standard Deviation 2.2
Standard Treatment Group	Comparison of Mean Pain Scores Between Two Arms (Measured Every 4 Hours Over 48 Hour)	2.8 0-10 units on a scale	Standard Deviation 3

Secondary

Breakthrough Narcotic Requirement

Rescue narcotic in both groups will be recorded and compared using a standard equianalgesic oral morphine equivalent (OME) calculation