Improving Post-Operative Pain and Recovery in Gynecologic Surgery

• Sponsor: Aultman Health Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT04175509
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Actual Duration (Months): 17.3
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This is a clinical investigation to determine the efficacy of rectal versus intravenous acetaminophen in patients undergoing a minimally invasive hysterectomy. All women will receive acetaminophen either rectally or intravenously immediately postoperative, prior to extubation. Patient's will be randomly assigned to either the rectal acetaminophen or the intravenous acetaminophen group. Patient outcomes will be measured through a Numeric Rating Scale (NRS) from 0-10 for pain scores, and total opioid consumption measured in morphine milligram equivalent (MME) for the first 24 hours following surgery, or upon discharge, whichever comes first.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Pain; Opioid Use; Acetaminophen	Drug: Rectal acetaminophen; Drug: Intravenous acetaminophen	Phase 4

Detailed Description

Patient's undergoing major gynecologic surgery require effective postoperative pain management in order to enhance recovery and ultimately allow patients to return to their preoperative functional state. Traditionally, acute postoperative pain control has been achieved largely with the use of opioid medications. Excessive use of opioids can have adverse effects on the recovery process. Side effects include, but are not limited to dizziness, sedation, nausea/vomiting, respiratory depression, euphoria, constipation, and abuse. In addition, opioid monotherapy can delay post-operative ambulation, contribute to prolonged hospital stay and resumption of activities of daily living, and furthermore, have long-term sequelae for individuals as well as society at whole.

Over the past decade, a multimodal approach to pain management has been explored in attempts to optimally treat acute postoperative pain. This approach is one of the keys to improving the recovery process.

Acetaminophen is a non-opioid analgesic with a well-established safety and tolerability profile that is commonly used in multimodal approach to treating surgical pain. It is available in oral, rectal and Intravenous (IV) formulation. IV acetaminophen in particular is increasingly used for pain control after surgery as it has demonstrated a significant analgesic benefit in a variety of surgery types by reduction in pain intensity while decreasing total opioid use. Many studies have evaluated the efficacy of acetaminophen based on route of administration. A systematic review demonstrated that there is no clear indication for intravenous acetaminophen for patients who can tolerate an oral dosage as there was no difference if efficacy outcomes. This is valuable information as the cost of IV acetaminophen is exponentially more than the oral form. Although the oral form of acetaminophen is as efficient as controlling pain when compared to IV, and is notably cheaper, it is not the best option for the nauseated patient or patients whom are restricted from oral intake following surgery. Rectal acetaminophen is therefore a feasible alternative option in such patients.

Data on the use of rectal acetaminophen in adults for postoperative pain management is limited. Pettersson and colleagues (2005) compared oral, rectal and IV paracetamol in day surgery patients. Although they demonstrated significantly higher plasma paracetamol concentrations in patients who received oral and IV formations at multiple time points, there was no difference in pain ratings. In another study, rectal paracetamol was shown to have a significant morphine-sparing effect after hysterectomy.

At this time, there has been no study in the gynecologic literature to compare IV to rectal acetaminophen in terms of pain control and effect on overall opioid use in the acute post-operative period.

The rationale for this study is to determine the optimal way of managing post-operative pain in gynecologic surgery in attempt to improve the overall recovery process. More specifically, this study will determine if the route of administration of acetaminophen has an effect on post-operative pain and use of opioid medication following a minimally invasive hysterectomy. The results of this study may guide post-operative pain management after gynecologic surgery, and help limit the amount of opioid use, while potentially reducing pharmacological costs for patients and hospitals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Supportive Care
• Official Title: Improving Post-Operative Pain and Recovery in Gynecologic Surgery
• Actual Study Start Date: Dec 23, 2019
• Actual Primary Completion Date: Jun 1, 2021
• Actual Study Completion Date: Jun 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Rectal acetaminophen Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery.	Drug: Rectal acetaminophen; Rectal 1300mg
Active Comparator: Intravenous acetaminophen Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery.	Drug: Intravenous acetaminophen; Intravenous 1000mg

Outcome Measures

Primary Outcome Measures

1. Postoperative Pain: Standardized Pain Scale [The first 24 hours following surgery, or upon discharge, whichever comes first.]

   Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) measured every 4 hours for the 24 hours, or discharge, whichever comes first. Time points were averaged for each participate and reported as a single value.

Secondary Outcome Measures

1. Opioid Use [The first 24 hours following surgery, or upon discharge, whichever comes first.]

   Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 24 hours following surgery, or upon discharge, whichever comes first.

Other Outcome Measures

1. Postoperative Pain: Standardized Pain Scale [The first 6 hours following surgery]

   Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) for the first 6 hours after surgery. Time points were averaged for each participate and reported as a single value.

2. Postoperative Pain: Standardized Pain Scale [The 12 hours following surgery]

   Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) for the first 12 hours after surgery. Time points were averaged for each participate and reported as a single value.

3. Opioid Use [The first 6 hours following surgery]

   Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 6 hours following surgery

4. Opioid Use [The first 12 hours following surgery]

   Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 12 hours following surgery

5. Estimated Blood Loss [During the duration of the surgery, from start to end time, on average 1.5 hours]

   Total estimated blood loss in millilitres for the surgery

6. Operative Time [From the start to end of the surgery]

   Operative time in minutes determined by the operating room record

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Willing to consent

• Amendable to receive either rectal or intravenous acetaminophen

• Planned hospital stay for at least 24 hours.

Exclusion Criteria:

• Patients unable to provide informed consent

• Patients with a history of regular opioid use prior to surgery based on their current home medication list

• Patients who have required regular opioid intake for the 7 days preceding surgery

• Patients with known hypersensitivity to acetaminophen

• Patients with a baseline preoperative liver function enzymes (AST and ALT) that are greater than twice the upper limits

• Unable to complete procedure as planned.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aultman Hospital	Canton	Ohio	United States	44710

Sponsors and Collaborators

• Aultman Health Foundation

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 12, 2019
• Informed Consent Form - Oct 28, 2019

More Information

Publications

• Cao X, et al. Effect of intraoperative or postoperative intravenous acetaminophen on postoperative pain scores and opioid requirements in abdominal and spinal surgery patients. Int J Clin Exp Med 11(4)4120-4125, 2018.
• Chou R, Gordon DB, de Leon-Casasola OA, Rosenberg JM, Bickler S, Brennan T, Carter T, Cassidy CL, Chittenden EH, Degenhardt E, Griffith S, Manworren R, McCarberg B, Montgomery R, Murphy J, Perkal MF, Suresh S, Sluka K, Strassels S, Thirlby R, Viscusi E, Walco GA, Warner L, Weisman SJ, Wu CL. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain. 2016 Feb;17(2):131-57. doi: 10.1016/j.jpain.2015.12.008. Erratum in: J Pain. 2016 Apr;17(4):508-10. Dosage error in article text.
• Cobby TF, Crighton IM, Kyriakides K, Hobbs GJ. Rectal paracetamol has a significant morphine-sparing effect after hysterectomy. Br J Anaesth. 1999 Aug;83(2):253-6.
• Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus Oral Acetaminophen for Pain: Systematic Review of Current Evidence to Support Clinical Decision-Making. Can J Hosp Pharm. 2015 May-Jun;68(3):238-47. Review.
• Petterson PH, Hein A, Owall A, Anderson RE, Jakobsson JG. Early bioavailability in day surgery: a comparison between orally, rectally, and intravenously administered paracetamol. J. of Ambulatory Surgery 12:27-30, 2005.
• Sconzo Jr FR, Ramamoorthy S. The role of multimodal analgesia in colorectal surgery: a review of clinical data and case-based presentations featuring Ofirmev (acetaminophen) injections. Diseases of the Colon & Rectum 58(2):1-15, 2015.

• Responsible Party: Michaela Beynon, Principal Investigator, Aultman Health Foundation
• ClinicalTrials.gov Identifier: NCT04175509
• Other Study ID Numbers: 2019.08.20.MB
• First Posted: Nov 25, 2019
• Last Update Posted: Jan 20, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Michaela Beynon, Principal Investigator, Aultman Health Foundation: Postoperative Pain; Minimally-invasive Hysterectomy; Opioid Use; Acetaminophen; Hysterectomy
• Additional relevant MeSH terms: Pain, Postoperative; Acetaminophen

Study Results

Participant Flow

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Period Title: Overall Study
STARTED	19	21
COMPLETED	17	19
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen	Total
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg	Total of all reporting groups
Overall Participants	17	19	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 82.4%	17 89.5%	31 86.1%
>=65 years	3 17.6%	2 10.5%	5 13.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.53 (13.64)	52.37 (14.08)	51.50 (13.70)
Sex: Female, Male (Count of Participants)
Female	17 100%	19 100%	36 100%
Male	0 0%	0 0%	0 0%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	17 100%	19 100%	36 100%
Indication for hysterectomy (Count of Participants)
Benign	11 64.7%	12 63.2%	23 63.9%
Malignant	6 35.3%	7 36.8%	13 36.1%
Diabetes Mellitus (Count of Participants)
Count of Participants [Participants]	4 23.5%	1 5.3%	5 13.9%
Hypertension (Count of Participants)
Count of Participants [Participants]	10 58.8%	7 36.8%	17 47.2%
Thyroid disease (Count of Participants)
Count of Participants [Participants]	1 5.9%	2 10.5%	3 8.3%
Pulmonary disease (Count of Participants)
Count of Participants [Participants]	5 29.4%	2 10.5%	7 19.4%
Anxiety and/or depression (Count of Participants)
Count of Participants [Participants]	7 41.2%	5 26.3%	12 33.3%
Obesity (Count of Participants)
Count of Participants [Participants]	11 64.7%	14 73.7%	25 69.4%
Pathology (Count of Participants)
Benign	12 70.6%	13 68.4%	25 69.4%
Malignant	5 29.4%	6 31.6%	11 30.6%

Outcome Measures

1. Primary Outcome

Title	Postoperative Pain: Standardized Pain Scale
Description	Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) measured every 4 hours for the 24 hours, or discharge, whichever comes first. Time points were averaged for each participate and reported as a single value.
Time Frame	The first 24 hours following surgery, or upon discharge, whichever comes first.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	19
Mean (Standard Deviation) [score on a scale]	2.82 (1.11)	3.18 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.378
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Opioid Use
Description	Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 24 hours following surgery, or upon discharge, whichever comes first.
Time Frame	The first 24 hours following surgery, or upon discharge, whichever comes first.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	19
Mean (Standard Deviation) [Morphine Milligram Equivalents]	25.75 (20.09)	23.71 (18.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.753
	Comments
	Method	t-test, 2 sided
	Comments

3. Other Pre-specified Outcome

Title	Postoperative Pain: Standardized Pain Scale
Description	Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) for the first 6 hours after surgery. Time points were averaged for each participate and reported as a single value.
Time Frame	The first 6 hours following surgery

Outcome Measure Data

Analysis Population Description

Two participants in the intravenous acetaminophen group were discharged home prior to 6 hours after surgery and therefore were not included in the analysis.

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	17
Mean (Standard Deviation) [score on a scale]	3.13 (1.36)	1.36 (1.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	t-test, 2 sided
	Comments

4. Other Pre-specified Outcome

Title	Postoperative Pain: Standardized Pain Scale
Description	Post-operative pain control using a standardized pain scale from 0 (no pain) to 10 (worse pain) for the first 12 hours after surgery. Time points were averaged for each participate and reported as a single value.
Time Frame	The 12 hours following surgery

Outcome Measure Data

Analysis Population Description

One participant in the rectal acetaminophen group, and 3 participants in the intravenous acetaminophen group were discharged home prior to 12 hours after surgery and therefore were not included in the analysis.

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	16	16
Mean (Standard Deviation) [score on a scale]	2.99 (1.20)	3.36 (1.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments

5. Other Pre-specified Outcome

Title	Opioid Use
Description	Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 6 hours following surgery
Time Frame	The first 6 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	17
Mean (Standard Deviation) [Morphine Milligram Equivalents]	6.74 (7.49)	7.97 (6.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.61
	Comments
	Method	t-test, 2 sided
	Comments

6. Other Pre-specified Outcome

Title	Opioid Use
Description	Total amount of opioid rescue calculated by converting all opiates to Morphine Milligram Equivalents in the first 12 hours following surgery
Time Frame	The first 12 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	16	16
Mean (Standard Deviation) [Morphine Milligram Equivalents]	15.52 (13.35)	14.17 (11.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	t-test, 2 sided
	Comments

7. Other Pre-specified Outcome

Title	Estimated Blood Loss
Description	Total estimated blood loss in millilitres for the surgery
Time Frame	During the duration of the surgery, from start to end time, on average 1.5 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	19
Mean (Standard Deviation) [Millilitres]	273.53 (138.20)	347.37 (75.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	t-test, 2 sided
	Comments

8. Other Pre-specified Outcome

Title	Operative Time
Description	Operative time in minutes determined by the operating room record
Time Frame	From the start to end of the surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rectal Acetaminophen	Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg	Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
Measure Participants	17	19
Mean (Standard Deviation) [Minutes]	88.71 (24.22)	90.89 (21.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rectal Acetaminophen, Intravenous Acetaminophen
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.78
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	From administration of acetaminophen until discharge from the hospital, up to 24 hours.
Arm/Group Title	Rectal Acetaminophen		Intravenous Acetaminophen
Arm/Group Description	Patients will receive two 650mg suppositories rectally of acetaminophen for a total dose of 1300mg at the end of surgery. Rectal acetaminophen: Rectal 1300mg		Patients will receive one dose of 1000mg of acetaminophen, administered intravenously, at the end of surgery. Intravenous acetaminophen: Intravenous 1000mg
All Cause Mortality
	Rectal Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Serious Adverse Events
	Rectal Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Rectal Acetaminophen		Intravenous Acetaminophen
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/21 (0%)

Limitations/Caveats

Due to the COVID-19 pandemic, many patients were prohibited to stay overnight in the hospital. Therefore, many patients were discharged home before 24 hours after surgery. This is primarily why the primary and secondary outcomes were analyzed at shorter time intervals (6 hours post-op and 12 hours-op) as well.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.