Background
Opioid overdose morbidity and mortality remain substantial public health threats in North America, particularly in the era of highly potent novel synthetic opioid agents [
1]. Mortality related to opioid overdose is also a global concern, with the greatest impact in North America, Europe, and Australasia [
2]. Contamination of the street drug supply with illicitly manufactured fentanyl (IMF) and its analogs has precipitated dramatic increases in mortality in the USA and Canada, representing a period of substantially increased risk for people who use drugs (PWUD) [
3]. As IMF contamination expands to illicit stimulant and other non-opioid substances, the potential number of opioid-naïve individuals at risk of opioid overdose has also increased [
4,
5].
Overdose prevention efforts include medications for opioid use disorder, overdose education and naloxone distribution (OEND) programs, overdose prevention sites and supervised consumption services, and drug testing services [
6‐
8]. Studies show that PWUD modify or adapt their drug use behavior in light of increased overdose risk associated with synthetic opioid contamination, including using smaller doses to test drug strength, maintaining consistent drug supply, consuming drugs with others present, reducing drug consumption, and having naloxone present [
9,
10]. However, as contamination of the drug supply with IMF becomes more prevalent, novel tools to prevent and respond to opioid overdose events are urgently needed.
In recent years, analytic tests to detect fentanyl contamination have received substantial attention [
11]. Traditional forensic testing technologies such as mass spectrometry can identify fentanyl and other synthetic analogs in drug samples, but are expensive and require specialized training and reagents [
12]. Rapid and simple point of care tests have been proposed as an alternative tool for increasing access to fentanyl testing services in highly marginalized communities, and in drug-using populations without access to supervised consumption facilities, as is currently the case in the USA. Paper-based immunoassays (e.g., Rapid Response™ fentanyl test strip, BTNX Corporation, Canada) provide similar sensitivity and specificity compared to portable mass spectrometers, with low technical requirements and results within 5 min [
13]. People who use drugs report interest in knowing if fentanyl is in their drugs prior to use, with high willingness and acceptability to use fentanyl test strips in the future [
14,
15]. Furthermore, early studies have shown that positive fentanyl test strip outcomes result in positive drug use behavior change, and participants report a desire to perform testing prior to drug use and in private locations [
16,
17]. Novel drug testing modalities that increase harm reduction self-efficacy will be paramount in assisting and supporting PWUD at risk of fentanyl overdose.
The study protocol described herein aims to test the efficacy of a novel behavior change intervention that incorporates fentanyl testing strips with a theory-driven opioid overdose risk reduction component. Guided by two health behavior frameworks, we hypothesize that combining motivational interviewing counseling techniques to increase willingness and self-efficacy to use fentanyl test strips with fentanyl test strip training and teach-back will result in enhanced overdose risk reduction practice, compared to participants receiving standard overdose education and naloxone training. We hypothesize that exposure to the Rhode Island Prescription and Illicit Drug Study (RAPIDS) intervention will reduce rates of fatal and non-fatal opioid overdose. Mediation analysis will assess the differential uptake of behavior changes in participants receiving the intervention.
Discussion
To date, no randomized clinical trials have examined the efficacy of rapid fentanyl test strips in combination with behavior change intervention for the prevention of opioid overdose events. Our pilot study of young people at risk of fentanyl exposure demonstrated a high willingness to use fentanyl test strips as a harm reduction tool and the feasibility of a brief training module for non-expert use [
14,
16]. Furthermore, positive test strip results were associated with drug risk behavior changes [
16]. The current randomized clinical trial aims to demonstrate the application of theory-driven motivational interviewing sessions that improve participant self-efficacy in drug risk behavior reduction alongside fentanyl test strip distribution and brief training in their use.
The results from this randomized clinical trial will need to be considered in light of some limitations. Firstly, participants are being drawn from an unknown sample frame and may not be representative of the greater population of PWUD in Rhode Island or other geographic locations. However, our participant recruitment and retention plan is informed by pilot studies of PWUD in Rhode Island and will consist of numerous and diverse strategies for participant engagement [
36]. Secondly, evaluating the effectiveness of a behavior change and fentanyl test strip intervention versus standard overdose education and naloxone distribution is complicated by the subjective nature of overdose events. Our measure of self-reported overdose captures participants’ perceived negative reactions of using drugs, in line with the literature [
29,
30]. In addition, we will collect symptomatology of overdose events to better describe the severity of non-fatal overdose events experienced by participants. To address issues with subjective measures of exposure to fentanyl, we have incorporated urine drug testing—for 12 drugs including fentanyl—in the protocol and a 3-day recall period for exposure to substances. Finally, loss to follow-up is a key issue for studies of PWUD, compounded by the illicit nature of substance use. We will implement comprehensive participant retention strategies, including text message and email reminders, participant honoraria and subsidized parking, and targeted canvassing in spaces where PWUD are known to frequent. To address potential bias related to loss to follow-up, administrative data linkage—capturing fatal overdose events reported by the medical examiner, and non-fatal overdose events attended to by emergency medical services or presented at emergency departments—will be utilized in exploratory analyses.
This randomized clinical trial serves as the first such work to evaluate the efficacy of novel drug testing technology combined with a behavioral change component. If found to be effective, the RAPIDS intervention will provide the basis for an affordable program that can be feasibly implemented by harm reduction services for the prevention of opioid overdoses around the world. In light of IMF contamination of non-opioid substances, novel interventions are necessary to protect the health of people who use drugs.
Trial status
Protocol version number and date: version 1.2; 19 March 2020
Expected date recruitment begins: 1 August 2020
Approximate date when recruitment will be completed: 31 August 2022
Acknowledgements
We would like to thank our colleagues Drs. Traci Green, Thomas Kerr, Josiah Rich, and Evan Wood for their contribution to the development and funding of the RAPIDS Clinical Trial.
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