DexMab: Dextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion

• Sponsor: Study Investigator-Sponsor (Other)
• Overall Status: Completed
• CT.gov ID: NCT03480009
• Collaborator: Society of Family Planning (Other)
• Enrollment: 156
• Locations: 2
• Arms: 4
• Actual Duration (Months): 11.1
• Patients Per Site: 78
• Patients Per Site Per Month: 7

Study Details

Study Description

Brief Summary

This study evaluates dextromethorphan as a non-opioid adjunctive medication for pain control during medication abortion. This is double-blinded, four-arm randomized controlled trial enrolling 156 women over a period of 9-12 months: Receiving narcotics+dextromethorphan, narcotics and placebo (microcrystalline cellulose), no narcotics and dextromethorphan and no narcotics and placebo (microcrystalline cellulose).

Condition or Disease	Intervention/Treatment	Phase
Abortion in First Trimester	Drug: Dextromethorphan Hydrobromide; Drug: Avicel PH101 (Microcrystalline Cellulose NF) for Compounding; Drug: Oxycodone	Phase 3

Detailed Description

Medication abortion using mifepristone and misoprostol is common, accounting for nearly one-third of abortions in the United States in 2014. Although women generally tolerate medical abortion well, pain and bleeding are common and expected side effects. Up to a quarter of women rate their pain as severe during their procedure. Pain management for medical abortion is challenging given that the most acute pain occurs at home rather than under the supervision of medical professionals. Currently there is insufficient evidence to recommend an optimal regimen for pain control in medication abortion and there are concerns surrounding narcotic prescribing and the opiate abuse epidemic. This is a four-arm, prospective, double-blind, randomized controlled trial comparing dextromethorphan administration in conjunction with the current standard regimen (NSAIDs and narcotic medication by request- commonly oxycodone or codeine) to the standard regimen alone. Pain will be evaluated by analgesia usage and self-reported pain scores. Investigators will also investigate factors influencing pain and subjective components of the patient narrative. Ideally, a non-opioid adjunct to NSAIDs or narcotics could be used to control pain and significantly curtail or avoid opioid use. Investigators seek to test the efficacy and safety of dextromethorphan as a non-narcotic analgesic for medication abortion.

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized Controlled TrialRandomized Controlled Trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dextromethorphan as a Novel Non-opioid Adjunctive Agent for Pain Control in Medication Abortion: a Randomized Controlled Trial
• Actual Study Start Date: Jul 28, 2018
• Actual Primary Completion Date: Jun 30, 2019
• Actual Study Completion Date: Jun 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dextromethorphan, opted for narcotic prescription Dextromethorphan hydrobromide and patient opts for narcotics (oxycodone or other standard narcotics)	Drug: Dextromethorphan Hydrobromide; Dextromethorphan capsule; Other Names: Robitussin, Delsym ; Drug: Oxycodone; Participants may opt for the narcotic receiving arms of the study, before being randomized to dextromethorphan/placebo.; Other Names: Tylox, Percodan, OxyContin
Placebo Comparator: Placebo, opted for narcotic prescription Avicel PH101 (Microcrystalline Cellulose NF) and patient opts for narcotics (oxycodone or other standard narcotics)	Drug: Avicel PH101 (Microcrystalline Cellulose NF) for Compounding; Placebo capsule; Other Names: Avicel ; Drug: Oxycodone; Participants may opt for the narcotic receiving arms of the study, before being randomized to dextromethorphan/placebo.; Other Names: Tylox, Percodan, OxyContin
Experimental: Dextromethorphan, declined narcotic prescription Dextromethorphan hydrobromide and patient declines narcotic	Drug: Dextromethorphan Hydrobromide; Dextromethorphan capsule; Other Names: Robitussin, Delsym
Placebo Comparator: Placebo, declined narcotic prescription Avicel PH101 (Microcrystalline Cellulose NF) for Compounding and patient declines narcotic	Drug: Avicel PH101 (Microcrystalline Cellulose NF) for Compounding; Placebo capsule; Other Names: Avicel

Outcome Measures

Primary Outcome Measures

1. Worst Pain Measurement Via Numeric Rating Scale (NRS-11) [Over 24 hours starting from misoprostol administration]

   Self-reported pain measurement via text-messaging system during first 24 hours after misoprostol administration. The scale is from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain possible".

2. Analgesic Usage During Medication Abortion [Over 24 hours]

   Analgesic usage by study arm for women who received dextromethorphan vs. placebo as adjunct to routine pain management during medication abortion; missing data are for participants who did not take the specified pain medication.

Secondary Outcome Measures

1. Mean Pain Scores Via Numeric Rating Scale (NRS-11) [Marginal mean pain scores over 24 hours]

   Marginal mean pain scores via Numeric Rating Scale (NRS-11) over 24 hours. The scale is from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain possible".

2. Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale [24 hours after misoprostol administration]

   Overall satisfaction with pain control, "4" being - "Very good" and "1" being "Very bad"

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women aged 18 and over

• Willing to give voluntary consent

• English-speaking

• Eligible for medication abortion per Planned Parenthood of Western Pennsylvania protocol

• Self-reported reliable cellular phone access for the duration of study participation

• Able to receive and reply to a "test" text at time of consent

• Willing to comply with the study protocol

Exclusion Criteria:

• Use of selective serotonin reuptake inhibitors or monoamine oxidase inhibitors due to risk of Serotonin Syndrome

• Allergy to any component of the medication abortion regimen or study drug

• Has any other condition that, in the opinion of the investigator, would preclude informed consent, make study participation unsafe, complicate the interpretation of the study outcome data, or otherwise interfere with achieving the study objectives

• Anticipated use of dextromethorphan during study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center for Family Planning Research, Magee-Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
2	Planned Parenthood of Western Pennsylvania	Pittsburgh	Pennsylvania	United States	15213

Sponsors and Collaborators

• Study Investigator-Sponsor
• Society of Family Planning

Investigators

• Principal Investigator: Principal Investigator, MD MPH, University of Pittsburgh

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 17, 2019

More Information

Publications

• Christie A, Dagfinrud H, Dale Ø, Schulz T, Hagen KB. Collection of patient-reported outcomes;--text messages on mobile phones provide valid scores and high response rates. BMC Med Res Methodol. 2014 Apr 16;14:52. doi: 10.1186/1471-2288-14-52.
• Ilkjaer S, Nielsen PA, Bach LF, Wernberg M, Dahl JB. The effect of dextromethorphan, alone or in combination with ibuprofen, on postoperative pain after minor gynaecological surgery. Acta Anaesthesiol Scand. 2000 Aug;44(7):873-7.
• Penney G. Treatment of pain during medical abortion. Contraception. 2006 Jul;74(1):45-7. Epub 2006 May 6. Review.
• Practice bulletin no. 143: medical management of first-trimester abortion. Obstet Gynecol. 2014 Mar;123(3):676-692. doi: 10.1097/01.AOG.0000444454.67279.7d.
• Weinbroum AA, Rudick V, Paret G, Ben-Abraham R. The role of dextromethorphan in pain control. Can J Anaesth. 2000 Jun;47(6):585-96. Review.

• Responsible Party: Study Investigator-Sponsor, Associate Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT03480009
• Other Study ID Numbers: STUDY19020221
• First Posted: Mar 27, 2018
• Last Update Posted: Aug 6, 2020
• Last Verified: Jul 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 Study Investigator-Sponsor, Associate Professor, University of Pittsburgh: medication abortion; dextromethorphan; pain control
• Additional relevant MeSH terms: Oxycodone; Dextromethorphan

Study Results

Participant Flow

Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription	Placebo, Opted for Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription
Arm/Group Description	Dextromethorphan hydrobromide and patient opts for narcotics (oxycodone or other standard narcotics) Participants may opt for the narcotic receiving arms of the study, before being randomized to dextromethorphan/placebo.	Avicel PH101 (Microcrystalline Cellulose NF) and patient opts for narcotics (oxycodone or other standard narcotics) Participants may opt for the narcotic receiving arms of the study, before being randomized to dextromethorphan/placebo.	Dextromethorphan hydrobromide and patient declines narcotic	Avicel PH101 (Microcrystalline Cellulose NF) and patient declines narcotic
Period Title: Overall Study
STARTED	62	62	16	16
COMPLETED	58	57	12	16
NOT COMPLETED	4	5	4	0

Baseline Characteristics

Arm/Group Title	Dextromethorphan, With Narcotic Prescription	Placebo, With Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription	Total
Arm/Group Description	Participants receiving dextromethorphan and a narcotic prescription	Participants receiving placebo and a narcotic prescription	Participants receiving dextromethorphan and declined a narcotic prescription	Participants receiving placebo and declined a narcotic prescription	Total of all reporting groups
Overall Participants	62	62	16	16	156
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.5 (5.4)	25.8 (4.4)	27.1 (5.0)	26.1 (5.3)	26.6 (5.0)
Sex: Female, Male (Count of Participants)
Female	62 100%	62 100%	16 100%	16 100%	156 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Race : Non-Hispanic, Black	19 30.6%	16 25.8%	2 12.5%	1 6.3%	38 24.4%
Race : Non-Hispanic, White	38 61.3%	38 61.3%	10 62.5%	11 68.8%	97 62.2%
Hispanic, Black	0 0%	0 0%	1 6.3%	1 6.3%	2 1.3%
Hispanic, White	1 1.6%	1 1.6%	1 6.3%	1 6.3%	4 2.6%
Other	4 6.5%	7 11.3%	2 12.5%	2 12.5%	15 9.6%
Prior medication abortion (Count of Participants)
Count of Participants [Participants]	12 19.4%	12 19.4%	1 6.3%	2 12.5%	27 17.3%

Outcome Measures

1. Primary Outcome

Title	Worst Pain Measurement Via Numeric Rating Scale (NRS-11)
Description	Self-reported pain measurement via text-messaging system during first 24 hours after misoprostol administration. The scale is from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain possible".
Time Frame	Over 24 hours starting from misoprostol administration

Outcome Measure Data

Analysis Population Description

Intention to treat population where all participants were analyzed as randomized. Missing worst pain responses were imputed as 10 being the worst pain possible.

Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription	Placebo, Opted for Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription
Arm/Group Description	Participants receiving dextromethorphan and opted for a narcotic prescription	Participants receiving placebo and opted for a narcotic prescription	Participants receiving dextromethorphan and declined a narcotic prescription	Participants receiving placebo and declined a narcotic prescription
Measure Participants	62	62	16	16
Median (Inter-Quartile Range) [score on a scale]	8.0	7.0	7.5	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Declined Narcotic Prescription, Placebo, Declined Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Analgesic Usage During Medication Abortion
Description	Analgesic usage by study arm for women who received dextromethorphan vs. placebo as adjunct to routine pain management during medication abortion; missing data are for participants who did not take the specified pain medication.
Time Frame	Over 24 hours

Outcome Measure Data

Analysis Population Description

Missing data are for participants who did not take the specified pain medication

Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription	Placebo, Opted for Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription
Arm/Group Description	Participants receiving dextromethorphan and opted for a narcotic prescription	Participants receiving placebo and opted for a narcotic prescription	Participants receiving dextromethorphan and declined a narcotic prescription	Participants receiving placebo and declined a narcotic prescription
Measure Participants	62	62	16	16
ibuprofen	800	600	800	1000
9acetaminophen	1000	1300	800	975
oxycodone	10	15	15

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments	Ibuprofen
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.81
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments	acetaminophen
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.24
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments	oxycodone
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.54
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Declined Narcotic Prescription, Placebo, Declined Narcotic Prescription
	Comments	Ibuprofen
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.61
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Declined Narcotic Prescription, Placebo, Declined Narcotic Prescription
	Comments	Acetaminophen
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.24
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Mean Pain Scores Via Numeric Rating Scale (NRS-11)
Description	Marginal mean pain scores via Numeric Rating Scale (NRS-11) over 24 hours. The scale is from 0 to 10, where 0 represents "no pain" and 10 represents "the worst pain possible".
Time Frame	Marginal mean pain scores over 24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription	Placebo, Opted for Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription
Arm/Group Description	Participants receiving dextromethorphan and opted for a narcotic prescription	Participants receiving placebo and opted for a narcotic prescription	Participants receiving dextromethorphan and declined a narcotic prescription	Participants receiving placebo and declined a narcotic prescription
Measure Participants	62	62	16	16
Mean (Standard Deviation) [score on a scale (NRS-11)]	2.93 (2.92)	2.96 (2.76)	2.70 (2.95)	2.41 (2.88)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.99
	Comments
	Method	Wald Chi Square
	Comments	Wald Chi Square from mixed effects linear regression

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Declined Narcotic Prescription, Placebo, Declined Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.56
	Comments
	Method	Wald Chi Square
	Comments	P-value from Wald chi-square from mixed effects linear regression

4. Secondary Outcome

Title	Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale
Description	Overall satisfaction with pain control, "4" being - "Very good" and "1" being "Very bad"
Time Frame	24 hours after misoprostol administration

Outcome Measure Data

Analysis Population Description

There are missing data for 3 participants in the dextromethorphan group (1 that opted for a narcotic prescription and 2 that declined) and 3 participants in the placebo (opted for narcotic prescription group).

Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription	Placebo, Opted for Narcotic Prescription	Dextromethorphan, Declined Narcotic Prescription	Placebo, Declined Narcotic Prescription
Arm/Group Description	Participants receiving dextromethorphan and opted for narcotic prescription	Participants receiving placebo and opted for narcotic prescription	Participants receiving dextromethorphan and declined narcotic prescription	Participants receiving placebo and declined a narcotic prescription
Measure Participants	61	59	14	16
Very poor	3 4.8%	0 0%	0 0%	0 0%
Poor	11 17.7%	4 6.5%	5 31.3%	3 18.8%
Good	27 43.5%	30 48.4%	7 43.8%	8 50%
Very good	20 32.3%	25 40.3%	2 12.5%	5 31.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Opted for Narcotic Prescription, Placebo, Opted for Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.07
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Dextromethorphan, Declined Narcotic Prescription
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.50
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	3-5 days after enrollment
Adverse Event Reporting Description	Adverse events were collected using text messaging at multiple timepoints (at baseline, misoprostol administration, and 2, 5, 8, and 24 hours after misoprostol) and by phone call 3-5 days later
Arm/Group Title	Dextromethorphan, Opted for Narcotic Prescription		Placebo, Opted for Narcotic Prescription		Dextromethorphan, Declined Narcotic Prescription		Placebo, Declined Narcotic Prescription
Arm/Group Description	Participants receiving dextromethorphan and opted for a narcotic prescription		Participants receiving placebo and opted for a narcotic prescription		Participants receiving dextromethorphan and declined a narcotic prescription		Participants receiving placebo and declined a narcotic prescription
All Cause Mortality
	Dextromethorphan, Opted for Narcotic Prescription		Placebo, Opted for Narcotic Prescription		Dextromethorphan, Declined Narcotic Prescription		Placebo, Declined Narcotic Prescription
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/62 (0%)		0/62 (0%)		0/16 (0%)		0/16 (0%)
Serious Adverse Events
	Dextromethorphan, Opted for Narcotic Prescription		Placebo, Opted for Narcotic Prescription		Dextromethorphan, Declined Narcotic Prescription		Placebo, Declined Narcotic Prescription
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		0/62 (0%)		0/16 (0%)		0/16 (0%)
Reproductive system and breast disorders
Uterine hemorrhage	1/62 (1.6%)	1	0/62 (0%)	0	0/16 (0%)	0	0/16 (0%)	0
Other (Not Including Serious) Adverse Events
	Dextromethorphan, Opted for Narcotic Prescription		Placebo, Opted for Narcotic Prescription		Dextromethorphan, Declined Narcotic Prescription		Placebo, Declined Narcotic Prescription
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/62 (58.1%)		28/62 (45.2%)		11/16 (68.8%)		8/16 (50%)
Gastrointestinal disorders
Nausea	28/62 (45.2%)		23/62 (37.1%)		10/16 (62.5%)		8/16 (50%)
Vomiting	14/62 (22.6%)		14/62 (22.6%)		6/16 (37.5%)		3/16 (18.8%)
Diarrhea	8/62 (12.9%)		13/62 (21%)		7/16 (43.8%)		4/16 (25%)
General disorders
Chills	10/62 (16.1%)		10/62 (16.1%)		5/16 (31.3%)		5/16 (31.3%)
Nervous system disorders
Dizziness	9/62 (14.5%)		7/62 (11.3%)		2/16 (12.5%)		1/16 (6.3%)
Drowsiness	12/62 (19.4%)		13/62 (21%)		3/16 (18.8%)		4/16 (25%)
Headache	6/62 (9.7%)		3/62 (4.8%)		1/16 (6.3%)		4/16 (25%)

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.