Drug Interactions
Conditions
Keywords
Drug Interactions, CYP2D6, opioid efficacy, pain, nausea
Brief summary
This study examines how hepatic cytochrome CYP2D6 drug interactions affects the efficacy of oxycodone, hydrocodone, and ondansetron in Emergency Department (ED) patients.
Detailed description
Patients with pain and/or nausea are enrolled in the Emergency Department (ED). They are given either oxycodone, hydrocodone, or ondansetron at the discretion of the Emergency Department (ED) provider or the triage nurse by triage protocol. Detailed prescription, over the counter, herbal, supplement, and illicit drug ingestion histories are taken from the patient or their health care proxy. Serial visual analogue scales are captured prior to study drug administration then between 30 and 90 minutes following drug administration.
Interventions
DRUGOxycodone
Subjects given oxycodone 5mg by ED provider decision or by triage nurse randomization.
DRUGHydrocodone
Subjects given hydrocodone/acetaminophen 5mg/500mg by ED provider decision or by triage nurse randomization.
DRUGOndansetron
Subjects given ondansetron 4mg for reported nausea or vomiting. Treatment determined either by triage nursing protocol or by provider discretion. Observational intervention only.
Sponsors
University of Colorado, Denver
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* self-reported pain or nausea identified by the initial nursing assessment
Exclusion criteria
* unable to speak English, * \< 18 y.o., * previously diagnosed with chronic pain or cyclic vomiting
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Clinically Significant Visual Analogue Scale for Pain and Nausea Change Between CYP2D6 Users and Non-users | Baseline and 90 minutes | Clinically significant visual analogue scale (VAS; a measure of adult pain and nausea on a scale of 1-100 millimeters for increasing symptoms of pain and nausea) for patients who were administered either oxycodone, hydrocodone/acetaminophen, or ondansetron in the ED. Clinically significant change was defined as 13mm change on the VAS from baseline (when first VAS was completed) to 90 minutes following drug administration in the ED. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Drug Events | Duration of ED stay, <24 hours. (up to 24 hours) | Determine all possible adverse drug events that occurred after the study drugs were administered. |
Countries
United States
Participant flow
Recruitment details
Recruitment was initiated in the University of Colorado Hospital ED. A convenience sample sample of ED patients were enrolled between June 2012 to January 2013. Subjects were included if they had self-reported pain or nausea identified during the initial nursing assessment. The previous 2 day medication history was obtained during their visit.
Pre-assignment details
201/502 consented patients did not receive the study medication. The remaining 301 patients were allocated to either one of the opioid treatment groups or the nausea observational group based on what study medication they were prescribed and if they were able to complete serial visual analog scales for pain and nausea.
Participants by arm
| Arm | Count |
|---|---|
| Oxycodone Group Subjects given oxycodone 5mg by ED provider decision or by triage nurse randomization. | 141 |
| Hydrocodone/Acetaminophen Group Subjects given hydrocodone/acetaminophen 5mg/500 mg by ED provider decision or by triage nurse randomization. | 91 |
| Nausea-observational Group Patients given ondansetron for reported nausea or vomiting by ED provider decision or by triage nurse. This is an observational cohort only. | 116 |
| Total | 348 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | No 2nd VAS | 16 | 8 | 23 |
Baseline characteristics
| Characteristic | Oxycodone Group | Hydrocodone/Acetaminophen Group | Nausea-observational Group | Total |
|---|---|---|---|---|
| Age, Continuous | 40 years | 38 years | 34 years | 40 years |
| Number of CYP2D6 drugs taken | 1 CYP2D6 drug | 1 CYP2D6 drug | 1 CYP2D6 drug | 1 CYP2D6 drug |
| Sex: Female, Male Female | 79 Participants | 56 Participants | 83 Participants | 218 Participants |
| Sex: Female, Male Male | 62 Participants | 35 Participants | 33 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 141 | 0 / 91 | 0 / 116 |
| serious Total, serious adverse events | 0 / 141 | 0 / 91 | 0 / 116 |
Outcome results
Primary
Difference in Clinically Significant Visual Analogue Scale for Pain and Nausea Change Between CYP2D6 Users and Non-users
Clinically significant visual analogue scale (VAS; a measure of adult pain and nausea on a scale of 1-100 millimeters for increasing symptoms of pain and nausea) for patients who were administered either oxycodone, hydrocodone/acetaminophen, or ondansetron in the ED. Clinically significant change was defined as 13mm change on the VAS from baseline (when first VAS was completed) to 90 minutes following drug administration in the ED.
Time frame: Baseline and 90 minutes
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Oxycodone Group | Difference in Clinically Significant Visual Analogue Scale for Pain and Nausea Change Between CYP2D6 Users and Non-users | 7.4 millimeters |
| Hydrocodone/Acetaminophen Group | Difference in Clinically Significant Visual Analogue Scale for Pain and Nausea Change Between CYP2D6 Users and Non-users | 10.9 millimeters |
| Nausea-observational Group | Difference in Clinically Significant Visual Analogue Scale for Pain and Nausea Change Between CYP2D6 Users and Non-users | -14.0 millimeters |
Secondary
Adverse Drug Events
Determine all possible adverse drug events that occurred after the study drugs were administered.
Time frame: Duration of ED stay, <24 hours. (up to 24 hours)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oxycodone Group | Adverse Drug Events | 0 participants |
| Hydrocodone/Acetaminophen Group | Adverse Drug Events | 0 participants |
| Nausea-observational Group | Adverse Drug Events | 0 participants |