Does IV Ondansetron Prevent Pruritus After Intrathecal Morphine in Pediatric Patients?

• Sponsor: University of Michigan (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03262038
• Collaborator: (none)
• Enrollment: 46
• Location: 1
• Arms: 2
• Actual Duration (Months): 20.4
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

This is a prospective randomized, double-blind, placebo-controlled study to compare the incidence and intensity of ITM-induced pruritus and nausea/vomiting using pre-emptive IV ondansetron, followed by scheduled Around The Clock (ATC) ondansetron vs. our control group, where pruritus and PONV are treated with PRN only medications.

Condition or Disease	Intervention/Treatment	Phase
Pruritus; Nausea/Vomiting	Drug: Ondansetron; Drug: Placebo Comparator	Phase 4

Detailed Description

Pruritus is one of the most common and bothersome side effects of intrathecal morphine (ITM) in children, with a reported incidence of 30-60%. Clinicians, who have witnessed unbearable itching and scratching in their young patients after intrathecal morphine, may be reluctant to offer this effective pain control to future patients, for fear of these unpleasant sequelae. A study previously found a 40% incidence of pruritus in young children who received intrathecal morphine for major urologic surgery.

This is a prospective randomized, double-blind, placebo-controlled study to compare the incidence and intensity of ITM-induced pruritus and nausea/vomiting using pre-emptive IV ondansetron, followed by scheduled Around The Clock (ATC) ondansetron vs. control group, where pruritus and PONV are treated with PRN only medications.

Enrollment of 3-17 year olds who are undergoing urologic or orthopedic operative procedures who are scheduled to receive low dose (4-5 mcg/kg) intrathecal morphine for pain management.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, double blinded, placebo-controlled trial of ondansetron to prevent pruritus in children who receive intrathecal morphineRandomized, double blinded, placebo-controlled trial of ondansetron to prevent pruritus in children who receive intrathecal morphine
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Study drug (ondansetron/placebo) will be masked for all but the pharmacist
• Primary Purpose: Prevention
• Official Title: A Randomized Double Blinded, Placebo-controlled Trial of IV Ondansetron to Prevent Pruritus in Children Who Receive Intrathecal Morphine
• Actual Study Start Date: Dec 7, 2017
• Actual Primary Completion Date: Aug 20, 2019
• Actual Study Completion Date: Aug 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ondansetron IV Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs)	Drug: Ondansetron; This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.
Placebo Comparator: Placebo Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4)	Drug: Placebo Comparator; This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.

Outcome Measures

Primary Outcome Measures

1. Incidence of Pruritus [24 hours]

   number of participants with any incidence of pruritus

2. Severity of Pruritus [24 hours]

   number of participants who indicated mild pruritus (no treatment needed) or severe pruritus (treatment needed)

Secondary Outcome Measures

1. Incidence of Post Operative Nausea or Vomiting [24 hours]

   number of participants with any incidence of postoperative nausea or vomiting

2. Severity of Post Operative Nausea or Vomiting [24 hours]

   number of participants who Indicated mild post operative nausea or vomiting (no treatment needed) or severe postoperative nausea or vomiting(treatment needed)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 3-17 years

• weight </= 100kg

• scheduled for urologic or orthopedic procedure necessitating intrathecal morphine

• ability to use verbal or pictorial pain assessment tools and techniques

• informed consent and (if applicable) assent

Exclusion Criteria:

• Inability to use verbal or pictorial pain scoring scales

• hypersensitivity to selective 5-HT receptor antagonists

• diagnosed congenital long QT syndrome

• severe hepatic impairment

• pregnancy or nursing mothers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Elizabeth Putnam, MD, University of Michigan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 3, 2018

More Information

Publications

None provided.

• Responsible Party: Elizabeth Putnam, Assistant Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT03262038
• Other Study ID Numbers: HUM00124202
• First Posted: Aug 25, 2017
• Last Update Posted: Jan 19, 2021
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Elizabeth Putnam, Assistant Professor, University of Michigan: intrathecal morphine
• Additional relevant MeSH terms: Pruritus; Vomiting; Ondansetron

Study Results

Participant Flow

Arm/Group Title	Ondansetron IV	Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
Period Title: Overall Study
STARTED	18	28
COMPLETED	18	27
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Ondansetron IV	Placebo	Total
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.	Total of all reporting groups
Overall Participants	18	27	45
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	8.3	8.2	8.3
Sex: Female, Male (Count of Participants)
Female	12 66.7%	17 63%	29 64.4%
Male	6 33.3%	10 37%	16 35.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	30.4	34.0	32.5
ASA 1, 2 (Count of Participants)
Count of Participants [Participants]	15 83.3%	27 100%	42 93.3%
Surgical Service (Count of Participants)
Urology	14 77.8%	22 81.5%	36 80%
Orthopedics	4 22.2%	5 18.5%	9 20%

Outcome Measures

1. Primary Outcome

Title	Incidence of Pruritus
Description	number of participants with any incidence of pruritus
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ondansetron IV	Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
Measure Participants	18	27
Count of Participants [Participants]	14 77.8%	24 88.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ondansetron IV, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.412
	Comments
	Method	Chi-squared
	Comments

2. Primary Outcome

Title	Severity of Pruritus
Description	number of participants who indicated mild pruritus (no treatment needed) or severe pruritus (treatment needed)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

Excludes those without any itch

Arm/Group Title	Ondansetron IV	Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
Measure Participants	14	24
Mild / no treatment needed	1 5.6%	4 14.8%
Severe / requiring treatment	13 72.2%	20 74.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ondansetron IV, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.633
	Comments
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Incidence of Post Operative Nausea or Vomiting
Description	number of participants with any incidence of postoperative nausea or vomiting
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ondansetron IV	Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
Measure Participants	18	27
Count of Participants [Participants]	8 44.4%	23 85.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ondansetron IV, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.007
	Comments
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Severity of Post Operative Nausea or Vomiting
Description	number of participants who Indicated mild post operative nausea or vomiting (no treatment needed) or severe postoperative nausea or vomiting(treatment needed)
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

excludes those without any nausea vomiting

Arm/Group Title	Ondansetron IV	Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.	Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
Measure Participants	8	23
Mild / no treatment required	2 11.1%	4 14.8%
Severe / requiring treatment	6 33.3%	19 70.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ondansetron IV, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.634
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	Adverse events were tracked through hospital discharge (approximately 24 hours)
Adverse Event Reporting Description	The AE reporting plan includes adverse events other than the two outcomes studied (AEs other than itch, nausea, or vomiting).
Arm/Group Title	Ondansetron IV		Placebo
Arm/Group Description	Ondansetron IV X1 intraoperatively (0.1 mg/kg in 5 mLs) Ondansetron IV X 4 (Q 6 hrs for 24 hrs) (0.1 mg/kg in 5 mLs) Ondansetron: This arm will receive (in a blinded fashion) 0.1 mg/kg of Ondansetron IV made up to 5 mLs intra-operatively and Ondansetron IV 0.1 mg/kg made up to 5 mLs every 6 hours for 24 hours postoperatively.		Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively X1 as well as IV every 6 hrs for 24 hours postoperatively. (X4) Placebo Comparator: This arm will receive (in a blinded fashion) a volume-matched placebo intraoperatively as well as IV every 6 hrs for 24 hours postoperatively.
All Cause Mortality
	Ondansetron IV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/27 (0%)
Serious Adverse Events
	Ondansetron IV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Ondansetron IV		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/27 (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.