Oxycodone Ingestion Patterns in Acute Fracture Pain With Digital Pills

Chai, Peter R. MD, MMS; Carreiro, Stephanie MD; Innes, Brendan J. BS; Chapman, Brittany BS; Schreiber, Kristin L. MD, PhD; Edwards, Robert R. PhD; Carrico, Adam W. PhD; Boyer, Edward W. MD, PhD

Disclosures

Anesth Analg. 2017;125(6):2105-2112. 

In This Article

Methods

Institutional Review Board and Patient Consent

This study was approved by our institutional review board; written informed consent was obtained from all study participants.

Digital Pill Technology

We utilized a digital pill system (eTectRx, Newbury, FL) (Figure 1) to measure opioid ingestion patterns. The digital pill system is an investigational device, classified by the Food and Drug Administration as a nonsignificant risk device. The digital pill comprises an ingestible radiofrequency emitter and a standard gelatin capsule sized to accept a single 5-mg oxycodone tablet. Each oxycodone digital pill contains its own unique radiofrequency emitter. When the digital pill is ingested, the gelatin capsule is dissolved, liberating the oxycodone tablet. Chloride ions energize the ingestible radiofrequency emitter that transmits a unique signal containing ingestion time and preprogrammed pill identification number. This signal is acquired by a cutaneous patch adhered to the abdominal wall. The patch is attached by a cable to a reader (approximately the size of an iPod) that stores and relays ingestion data through cellular signaling to a cloud-based server that collates and displays ingestion events. On capturing the radiofrequency signal, the reader also sends a text message to the investigational staff and study participants confirming the ingestion event. The reader only needs 2–3 seconds to capture the transmitted signal from the digital pill. The digital pill has been utilized without evidence of retention of the radiofrequency transmitter in the gut, and no adverse events have been reported in previous safety trials.[16] Digital pills were packaged in a standard blister pack; there was no particular order in which participants were required to take digital pills. A total of 21 dosage units (eg, twenty-one 5-mg oxycodone digital pills) were dispensed to each study participant.

Figure 1.

The digital pill comprised of an ingestible radiofrequency emitter combined with a gelatin capsule (A) sized to accept an oxycodone tablet (B) creating an oxycodone digital pill (C). The reader is composed of an adherent sticker attached by a cable to the reader that records ingestion events from the digital pill.

Design

This manuscript adheres to the applicable transparent reporting of evaluations with nonrandomized designs (TREND) guidelines.[20] We performed a descriptive study of opioid-naive adults discharged from a tertiary care ED between February 2016 and November 2016 with a diagnosis of acute fracture. We excluded individuals who had previous psychiatric and drug abuse histories, were admitted for fracture care, lived outside our catchment area and therefore would be unable to follow-up with us, or had multiple sites of injury. Trained research assistants (RAs) used the electronic medical record to screen ED patients for inclusion/exclusion criteria before approaching them for participation in the study. Eligible participants were approached in the ED and enrolled on a convenience basis pending the availability of the RA and an investigator. Participants were only able to be recruited during the times the investigational pharmacy was open (8 AM–5 PM, weekdays) as digital pill oxycodone was dispensed by our investigational pharmacy for this study. After providing written informed consent, participants before discharge received a 15-minute training session from the RA on the operation of the oxycodone digital pill before discharge. A study investigator (P.R.C., S.C., or E.W.B.) filled out a prescription for oxycodone digital pills for the hospital investigational pharmacy to dispense oxycodone digital pills to participants before their discharge from the ED. Participants then demonstrated use of each component; we verified successful use of the technology once participants had ingested the digital pill and received a text message confirming ingestion.

We instructed participants to use oxycodone (one to two 5-mg oxycodone digital pills every 6–8 hours) as needed for pain and ensured that study participants did not receive additional prescriptions for opioid analgesics at discharge from the ED, orthopedic services, or their primary care physician. Participants returned equipment and unused digital pills to our clinical research center at the end of 7 days or at the time of their follow-up orthopedic clinic visit. During this visit, we reviewed ingestion data with participants and conducted a pill count to assess the validity of the digital pill measurement. We also asked participants about their subjective quality of pain control and their decision-making process regarding whether and when to taper oxycodone use. Participants were remunerated for their participation in the study.

Statistical Analysis

Oxycodone ingestions were measured by the digital pill system and collated on a Research Electronic Data Capture database. Results were downloaded, and basic descriptive statistics were calculated on Microsoft Excel (Redmond, WA). Ingestion of the oxycodone digital pill associated with system training in the ED was marked time as 0; the study period ran for the next 7 days from this timepoint. If a patient reported adequate pain management at the time of system training, time 0 for the study period was time of patient discharge. Ingestions were defined as taking place on day 1 if they were recorded between time 0 and 24 hours, day 2 from 25 to 48 hours, day 3 from 49 to 72 hours, etc. Ingestion of oxycodone digital pills was recorded for 7 days; we calculated dose amount and dosing interval using ingestion data downloaded from our study server.

Patients were prescribed one to two 5-mg oxycodone digital pills every 6 to 8 hours as needed for pain. We calculated dosing interval by dividing 24 hours by the average number of doses taken in a day across all participants. A dose was defined as taking one or two 5-mg oxycodone digital pills at the same time. If a participant took two 5-mg oxycodone digital pills at 1 time, we considered that 1 dose of 10 mg. Because of the sample size, we calculated the median dose ingestion over the study period and median dose ingestions per day for the entire set of participants. We separated participants into those who required operative management of their fracture and those who were managed nonoperatively. We then calculated median ingestion amount and dosing interval for each group.

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