Postoperative Belladonna and Morphine Suppositories in Vaginal Surgery

• Sponsor: Kristina A. Butler (Other)
• Overall Status: Completed
• CT.gov ID: NCT01150474
• Collaborator: (none)
• Enrollment: 103
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 2.9

Study Details

Study Description

Brief Summary

Our primary aim is to determine whether the routine use of belladonna and morphine suppositories will improve pain control following vaginal surgery. Treatment will begin immediately following surgery and every 8 hours for 16 hours.

Condition or Disease	Intervention/Treatment	Phase
Vaginal Surgery	Drug: Belladonna and Opium Suppositories; Drug: Placebo Suppositories	Phase 4

Detailed Description

Minimizing postoperative pain is vital to a successful surgical recovery. Inadequate pain control may result in nausea, vomiting, an extended hospital stay, and reduced patient satisfaction. Oral and parenteral narcotics are commonly used for pain relief and their use may exacerbate the incidence of sedation, nausea, and vomiting; ultimately delaying convalescence. Previous studies have demonstrated that rectal analgesia following surgery results in lower pain scores and less intravenous morphine consumption. Belladonna and opium suppositories are routinely prescribed at our institution and their efficacy has not been confirmed.

A prospective, randomized, double-blind, placebo-controlled trial will be undertaken using belladonna and opium rectal suppositories following vaginal surgery. Treatment will begin immediately following surgery and continue every 8 hours for a total of 3 doses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Clinical Trial of Postoperative Belladonna and Morphine Suppositories in Vaginal Surgery
• Study Start Date: Jan 1, 2011
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Belladonna and Opium Suppositories Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Drug: Belladonna and Opium Suppositories; Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.; Other Names: B & O Supprettes
Placebo Comparator: Placebo Suppositories Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Drug: Placebo Suppositories; Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.

Outcome Measures

Primary Outcome Measures

1. Pain at Hour 4 [4 hours following surgery]

   Pain at 4 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."

Secondary Outcome Measures

1. Pain at Hour 12 [12 hours after surgery.]

   Pain at 12 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."

2. Pain at Hour 20 [20 hours after surgery.]

   Pain at 20 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."

3. Narcotic Rescue Medication [For 24 hours following surgery]

   Use of all ancillary narcotic medications was taken from the medical record.

4. Number of Subjects With Nausea [Approximately 12 hours after surgery]

   This information was taken from the medical record.

5. Number of Subjects With Vomiting [Within 20 hours of surgery]

   This information was taken from the medical record.

6. Number of Times Antiemetic Rescue Medication Was Used [First 24 hours after surgery]

7. Number of Subjects Who Used Antiemetic Rescue Medications [First 24 hours after surgery]

8. Satisfaction With Pain Relief [Approximately 24 hours following surgery]

   Patient satisfaction with pain relief was evaluated 24 hours after surgery using a linear analog satisfaction scale, with 0 being "very dissatisfied," and 10 being "very satisfied."

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Scheduled for elective vaginal surgery requiring general anesthesia at the Mayo Clinic Hospital. This would include a vaginal hysterectomy with culdoplasty or post-hysterectomy prolapse repair, including culdoplasty with or without anterior/posterior repair.

Exclusion Criteria:

• Participation in another trial using an investigational product.

• Pregnancy.

• Scheduled for a non-vaginal surgical procedure.

• Scheduled for a robotic hysterectomy.

• Scheduled to have combined surgeries (vaginal surgery plus another non-vaginal surgery).

• There is a known hypersensitivity to belladonna and/or opium.

• Contraindication to narcotic use.

• Chronic pain with preoperative pain score greater than 4 out of 10 points.

• Clinically significant substance abuse.

• Mental condition that may impair the ability to provide study assessments.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054

Sponsors and Collaborators

• Kristina A. Butler

Investigators

• Principal Investigator: Kristina Butler, M.D., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kristina A. Butler, M.D., Mayo Clinic
• ClinicalTrials.gov Identifier: NCT01150474
• Other Study ID Numbers: 09-008045
• First Posted: Jun 25, 2010
• Last Update Posted: Jan 7, 2015
• Last Verified: Dec 1, 2014

• Keywords provided by Kristina A. Butler, M.D., Mayo Clinic: Belladonna; Morphine; Suppositories; Vaginal; Surgery; Postoperative; Pain

Study Results

Participant Flow

Recruitment Details	Subjects were recruited at the Mayo Clinic in Arizona, United States from January 2011 to April 2013.

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Period Title: Overall Study
STARTED	51	52
COMPLETED	41	49
NOT COMPLETED	10	3

Baseline Characteristics

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories	Total
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Total of all reporting groups
Overall Participants	41	49	90
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (12)	55 (13)	55 (12.5)
Sex: Female, Male (Count of Participants)
Female	41 100%	49 100%	90 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	41 100%	49 100%	90 100%
Pelvic Organ Prolapse (participants) [Number]
Prolapse	21 51.2%	25 51%	46 51.1%
No Prolapse	20 48.8%	24 49%	44 48.9%
Procedure time (minutes) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [minutes]	98 (37)	96 (38)	97 (37)
Estimated Blood Loss (mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mL]	180 (250)	150 (110)	161 (186)
Preoperative Pain (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	0.44 (1.25)	0.24 (0.91)	0.3 (1.07)

Outcome Measures

1. Primary Outcome

Title	Pain at Hour 4
Description	Pain at 4 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."
Time Frame	4 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [units on a scale]	4.2 (2.4)	4.1 (2.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.82
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Pain at Hour 12
Description	Pain at 12 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."
Time Frame	12 hours after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [units on a scale]	3.4 (2.4)	3.3 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.75
	Comments
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Pain at Hour 20
Description	Pain at 20 hours was recorded using a linear analog pain scale, with 0 being "no pain," and 10 being "worst pain imaginable."
Time Frame	20 hours after surgery.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [units on a scale]	2.5 (1.9)	3.4 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Narcotic Rescue Medication
Description	Use of all ancillary narcotic medications was taken from the medical record.
Time Frame	For 24 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [mg IV morphine equivalents]	57 (38)	66 (61)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.43
	Comments
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	Number of Subjects With Nausea
Description	This information was taken from the medical record.
Time Frame	Approximately 12 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Number [participants]	14 34.1%	22 44.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Number of Subjects With Vomiting
Description	This information was taken from the medical record.
Time Frame	Within 20 hours of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Number [participants]	13 31.7%	9 18.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Number of Times Antiemetic Rescue Medication Was Used
Time Frame	First 24 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [number of times antiemetics used]	1.7 (1.6)	1.6 (1.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.83
	Comments
	Method	t-test, 2 sided
	Comments

8. Secondary Outcome

Title	Number of Subjects Who Used Antiemetic Rescue Medications
Time Frame	First 24 hours after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Number [participants]	30 73.2%	33 67.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	t-test, 2 sided
	Comments

9. Secondary Outcome

Title	Satisfaction With Pain Relief
Description	Patient satisfaction with pain relief was evaluated 24 hours after surgery using a linear analog satisfaction scale, with 0 being "very dissatisfied," and 10 being "very satisfied."
Time Frame	Approximately 24 hours following surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Belladonna and Opium Suppositories	Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.	Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
Measure Participants	41	49
Mean (Standard Deviation) [units on a scale]	8.2 (2.5)	7.9 (2.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Belladonna and Opium Suppositories, Placebo Suppositories
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.59
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Subjects will be followed for 24 hours after surgery, and the research coordinator will assess for adverse events one week after surgery via the electronic medical record.
Arm/Group Title	Belladonna and Opium Suppositories		Placebo Suppositories
Arm/Group Description	Belladonna (16.2 mg) and opium (60 mg) suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.		Placebo suppositories administered rectally immediately following surgery and every 8 hours for 16 hours for a total of 3 doses.
All Cause Mortality
	Belladonna and Opium Suppositories		Placebo Suppositories
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Belladonna and Opium Suppositories		Placebo Suppositories
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		0/49 (0%)
General disorders
Abdominal Sepsis	1/41 (2.4%)	1	0/49 (0%)	0
Other (Not Including Serious) Adverse Events
	Belladonna and Opium Suppositories		Placebo Suppositories
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/41 (58.5%)		27/49 (55.1%)
Blood and lymphatic system disorders
Anemia Postoperative	3/41 (7.3%)	3	0/49 (0%)	0
Cardiac disorders
Procedural Hypertension	1/41 (2.4%)	1	0/49 (0%)	0
Sinus Tachycardia	1/41 (2.4%)	1	0/49 (0%)	0
Procedural Hypotension	1/41 (2.4%)	1	3/49 (6.1%)	3
Gastrointestinal disorders
Postoperative Ileus	1/41 (2.4%)	1	0/49 (0%)	0
Constipation	20/35 (57.1%)	20	27/46 (58.7%)	27
Renal and urinary disorders
Urinary Retention	21/41 (51.2%)	21	23/49 (46.9%)	23
Urinary Tract Infection	1/41 (2.4%)	1	0/49 (0%)	0
Respiratory, thoracic and mediastinal disorders
Sleep Apnea Syndrome	0/41 (0%)	0	1/49 (2%)	1
Skin and subcutaneous tissue disorders
Pruritis Generalized	1/41 (2.4%)	1	0/49 (0%)	0

Limitations/Caveats

[Not Specified]

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.