Abortion in First Trimester
Conditions
Keywords
medication abortion, dextromethorphan, pain control
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).
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.
Interventions
Dextromethorphan capsule
DRUGAvicel PH101 (Microcrystalline Cellulose NF) for Compounding
Placebo capsule
DRUGOxycodone
Participants may opt for the narcotic receiving arms of the study, before being randomized to dextromethorphan/placebo.
Sponsors
Society of Family Planning
Study Investigator-Sponsor
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized Controlled Trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dextromethorphan, With Narcotic Prescription Participants receiving dextromethorphan and a narcotic prescription | 62 |
| Placebo, With Narcotic Prescription Participants receiving placebo and a narcotic prescription | 62 |
| Dextromethorphan, Declined Narcotic Prescription Participants receiving dextromethorphan and declined a narcotic prescription | 16 |
| Placebo, Declined Narcotic Prescription Participants receiving placebo and declined a narcotic prescription | 16 |
| Total | 156 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 5 | 4 | 0 |
Baseline characteristics
| Characteristic | Placebo, With Narcotic Prescription | Total | Placebo, Declined Narcotic Prescription | Dextromethorphan, With Narcotic Prescription | Dextromethorphan, Declined Narcotic Prescription |
|---|---|---|---|---|---|
| Age, Continuous | 25.8 years STANDARD_DEVIATION 4.4 | 26.6 years STANDARD_DEVIATION 5 | 26.1 years STANDARD_DEVIATION 5.3 | 27.5 years STANDARD_DEVIATION 5.4 | 27.1 years STANDARD_DEVIATION 5 |
| Prior medication abortion | 12 Participants | 27 Participants | 2 Participants | 12 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic, Black | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic, White | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 15 Participants | 2 Participants | 4 Participants | 2 Participants |
| Race/Ethnicity, Customized Race : Non-Hispanic, Black | 16 Participants | 38 Participants | 1 Participants | 19 Participants | 2 Participants |
| Race/Ethnicity, Customized Race : Non-Hispanic, White | 38 Participants | 97 Participants | 11 Participants | 38 Participants | 10 Participants |
| Sex: Female, Male Female | 62 Participants | 156 Participants | 16 Participants | 62 Participants | 16 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 62 | 0 / 62 | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 36 / 62 | 28 / 62 | 11 / 16 | 8 / 16 |
| serious Total, serious adverse events | 1 / 62 | 0 / 62 | 0 / 16 | 0 / 16 |
Outcome results
Primary
Analgesic Usage During Medication Abortion
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
Population: Missing data are for participants who did not take the specified pain medication
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dextromethorphan, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | ibuprofen | 800 mg |
| Dextromethorphan, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | 9acetaminophen | 1000 mg |
| Dextromethorphan, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | oxycodone | 10 mg |
| Placebo, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | 9acetaminophen | 1300 mg |
| Placebo, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | ibuprofen | 600 mg |
| Placebo, Opted for Narcotic Prescription | Analgesic Usage During Medication Abortion | oxycodone | 15 mg |
| Dextromethorphan, Declined Narcotic Prescription | Analgesic Usage During Medication Abortion | 9acetaminophen | 800 mg |
| Dextromethorphan, Declined Narcotic Prescription | Analgesic Usage During Medication Abortion | ibuprofen | 800 mg |
| Placebo, Declined Narcotic Prescription | Analgesic Usage During Medication Abortion | 9acetaminophen | 975 mg |
| Placebo, Declined Narcotic Prescription | Analgesic Usage During Medication Abortion | oxycodone | 15 mg |
| Placebo, Declined Narcotic Prescription | Analgesic Usage During Medication Abortion | ibuprofen | 1000 mg |
Comparison: Ibuprofenp-value: 0.81Wilcoxon (Mann-Whitney)
Comparison: acetaminophenp-value: 0.24Wilcoxon (Mann-Whitney)
Comparison: oxycodonep-value: 0.54Wilcoxon (Mann-Whitney)
Comparison: Ibuprofenp-value: 0.61Wilcoxon (Mann-Whitney)
Comparison: Acetaminophenp-value: 0.24Wilcoxon (Mann-Whitney)
Primary
Worst Pain Measurement Via Numeric Rating Scale (NRS-11)
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Dextromethorphan, Opted for Narcotic Prescription | Worst Pain Measurement Via Numeric Rating Scale (NRS-11) | 8.0 score on a scale |
| Placebo, Opted for Narcotic Prescription | Worst Pain Measurement Via Numeric Rating Scale (NRS-11) | 7.0 score on a scale |
| Dextromethorphan, Declined Narcotic Prescription | Worst Pain Measurement Via Numeric Rating Scale (NRS-11) | 7.5 score on a scale |
| Placebo, Declined Narcotic Prescription | Worst Pain Measurement Via Numeric Rating Scale (NRS-11) | 6.5 score on a scale |
p-value: 0.2Wilcoxon (Mann-Whitney)
p-value: 0.2Wilcoxon (Mann-Whitney)
Secondary
Mean Pain Scores Via Numeric Rating Scale (NRS-11)
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dextromethorphan, Opted for Narcotic Prescription | Mean Pain Scores Via Numeric Rating Scale (NRS-11) | 2.93 score on a scale (NRS-11) | Standard Deviation 2.92 |
| Placebo, Opted for Narcotic Prescription | Mean Pain Scores Via Numeric Rating Scale (NRS-11) | 2.96 score on a scale (NRS-11) | Standard Deviation 2.76 |
| Dextromethorphan, Declined Narcotic Prescription | Mean Pain Scores Via Numeric Rating Scale (NRS-11) | 2.70 score on a scale (NRS-11) | Standard Deviation 2.95 |
| Placebo, Declined Narcotic Prescription | Mean Pain Scores Via Numeric Rating Scale (NRS-11) | 2.41 score on a scale (NRS-11) | Standard Deviation 2.88 |
p-value: 0.99Wald Chi Square
p-value: 0.56Wald Chi Square
Secondary
Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale
Overall satisfaction with pain control, 4 being - Very good and 1 being Very bad
Time frame: 24 hours after misoprostol administration
Population: 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 | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dextromethorphan, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very poor | 3 Participants |
| Dextromethorphan, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Poor | 11 Participants |
| Dextromethorphan, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Good | 27 Participants |
| Dextromethorphan, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very good | 20 Participants |
| Placebo, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Poor | 4 Participants |
| Placebo, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Good | 30 Participants |
| Placebo, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very good | 25 Participants |
| Placebo, Opted for Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very poor | 0 Participants |
| Dextromethorphan, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Good | 7 Participants |
| Dextromethorphan, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Poor | 5 Participants |
| Dextromethorphan, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very good | 2 Participants |
| Dextromethorphan, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very poor | 0 Participants |
| Placebo, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very good | 5 Participants |
| Placebo, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Poor | 3 Participants |
| Placebo, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Very poor | 0 Participants |
| Placebo, Declined Narcotic Prescription | Number of Participants With Pain Control Satisfaction Via 4-pt Likert Scale | Good | 8 Participants |
p-value: 0.07Fisher Exact
p-value: 0.5Fisher Exact