Risks and Benefits of Naloxone Prescribing
Condition: Opioid Overdose
MeSH terms: Drug Overdose; Opiate Overdose
Study type: Interventional

Summary: 
      This investigation is one of the first large-scale, prospective attempts to obtain data on
      the effectiveness of naloxone distribution among opioid-abusing populations at high risk of
      unintentional opioid poisoning. Specifically, opioid abusers will be recruited from drug
      detoxification sites as well as those accessing services at needle exchange programs. All
      participants (N=700) will receive the standard opioid overdose education and naloxone. One
      third of the participants will be randomized to receive additional in-depth psychosocial
      education focusing on recognition and prevention of opioid overdose, and appropriate use of
      naloxone. Another third of the participants will receive the extensive training and be
      required to engage a spouse, partner, relative, or friend in this supplementary intervention.
      The investigators plan to randomize individuals to each group [Treatment as Usual (TAU) vs.
      Extensively Trained (ET) vs. Extensively Trained with a Significant Other (ETwSO)] and,
      through continued follow up over one year, the investigators will compare self-reported
      overdose reversal attempts (with and without naloxone use), naloxone-related adverse events,
      and changes in patterns of heroin and other drug use.
    

Detailed description: 
      Study Design A significant cause of mortality among opioid users is overdose, which commonly
      occurs following voluntary (opioid detoxification) or involuntary (incarceration) opioid
      abstinence. For the purposes of the current application, opioid overdose is defined as use of
      an opioid in an amount that results in over-sedation and/or respiratory depression requiring
      intervention by medical or non-medical persons. Nearly 85% of overdoses occur in the presence
      of a witness. Common methods of intervention by individuals without medical training are
      ineffective techniques such as shaking the victim or injecting salt water. Naloxone is an
      opioid antagonist that has long been used successfully by trained medical personnel during
      emergency resuscitation following opioid overdose. In an effort to reduce fatal and non-fatal
      opioid overdose, a number of states are implementing programs in which non-medical personnel
      are provided brief instruction in recognizing the signs of opioid overdose and administering
      naloxone. However, most of the existing programs are not designed to collect empirical data
      on the safety and effectiveness of this intervention. Reporting of naloxone use is voluntary
      and without incentive, and the experience of those who have been trained and prescribed
      naloxone is not followed.

      The proposed investigation will be one of the first large-scale, prospective attempts to
      obtain data on the effectiveness of naloxone distribution among opioid-abusing populations at
      high risk of unintentional opioid poisoning. Specifically, opioid abusers will be recruited
      from drug detoxification sites as well as those accessing services at needle exchange
      programs. All participants (N=700) will receive the standard opioid overdose education and
      naloxone. One third of the participants will be randomized to receive additional in-depth
      psychosocial education focusing on recognition and prevention of opioid overdose, and
      appropriate use of naloxone. Another third of the participants will receive the extensive
      training and be required to engage a spouse, partner, relative, or friend in this
      supplementary intervention. We plan to randomize individuals to each group [Treatment as
      Usual (TAU) vs. Extensively Trained (ET) vs. Extensively Trained with a Significant Other
      (ETwSO)] and, through continued follow up over one year, we will compare self-reported
      overdose reversal attempts (with and without naloxone use), naloxone-related adverse events,
      and changes in patterns of heroin and other drug use. In addition to comparing outcome
      variables in the TAU, ET and ETwSO groups prospectively, we will analyze data collected
      before study initiation to compare fatal and non-fatal opioid overdose rates in neighborhoods
      with facilities that offer overdose prevention training and naloxone to those that do not,
      using data provided by our collaborators at the New York City (NYC) Department of Health and
      Mental Hygiene (DOHMH).

      Specific Aims and Hypotheses

        -  Primary Aim (Prospective Study): Determine the extent to which additional psychosocial
           intervention can improve the effectiveness of current overdose prevention training as
           measured by:

        -  increased frequency of naloxone use (ETwSO > ET > TAU)

        -  decreased number of opioid overdoses (ETwSO < ET < TAU)

        -  improved recognition of opioid overdose and naloxone indication knowledge (increased
           BORRA scores; ETwSO > ET > TAU)

        -  Secondary Aim (Prospective Study): Determine the potential harms of this novel
           naloxone-prescribing practice as measured by:

        -  proportion of participants calling 911 in response to an overdose, compared to
           participants' recent history of calling 911 in response to an overdose

        -  risky drug use behavior (e.g. increased heroin/prescription opioid use, increased use of
           illicit drug combinations) following training, compared to pre-training

      Outcome Measures

      Primary Outcome Measures (Prospective Study): Determine the extent to which additional
      psychosocial intervention can improve upon the effectiveness of current overdose prevention
      training by: 1) increasing the frequency of naloxone use among ET participants (continuous
      variable); 2) decreasing the number of lethal opioid overdoses witnessed and experienced by
      the ET group (continuous variable); 3) improving accurate recognition of opioid overdose and
      naloxone indication knowledge (increased Brief Overdose Recognition and Response Assessment
      (BORRA) score among ET participants (continuous variable). These variables will be assessed
      repeatedly over the course of 1 year at: baseline (BL), immediately post-training (T0), 1-,
      3-, 6- and 12-months (T1, T3, T6, and T12). The frequency of naloxone use and outcomes of the
      overdose reversal attempts will be measured at T1, T3, T6, and T12 only.

      Secondary Outcome Measures (Prospective Study): Evaluate the potential harms of this novel
      naloxone-prescribing practice as assessed by: 1) decreased proportion of 911 calls in
      response to an overdose, compared to participants' previous history of calling 911 while
      witnessing an overdose (continuous variable); 2) changes in the use of illicit opioids, other
      illegal drugs, or drug combinations following training (longitudinal continuous variable); 3)
      prevalence of adverse events related to naloxone administration by non-medical personnel
      (continuous variable).
    

Intervention name(s): Extensive training
Intervention type(s): Other
Intervention description(s): We have developed a more in-depth education package to help participants better recognize and respond to an opioid overdose.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Health Services Research