A computer-generated 1:1 randomization schedule along with primary labeling for placebo and active naloxone study packs were provided by the packager. Each study pack contained 2 vials, 1 of which was labeled intramuscular and the other intranasal; 1 contained active naloxone, and the other contained placebo solution (water from Sypharma and saline from GD Pharma). The packs were sequentially numbered, coded according to the treatment arm, and allocated sequentially to participants in strict order of their registration for the trial. All vials for use in the study were identical in design and labeling apart from study codes. No direct contact at any stage occurred between the generator and executors of the assignment, which meant the participants, the nurses administering the naloxone, and the researchers were all blinded to the 2 treatment arms. Treatment allocations were decoded after statistical analysis.
Details of treatment methods are described in detail in the study protocol. Briefly, MSIC staff managed drug overdoses using existing clinical protocols. These protocols state that a client would receive airway management and oxygenation either via a mask or artificial ventilation (bagging) for 5 minutes and then would be assessed for the need for naloxone. If a consenting client’s response after 5 minutes was inadequate (oxygen saturation not maintained at ≥95% or with GCS score <13 or RR <10), the client was enrolled into the study, and trial drugs were administered by a registered nurse in accordance with existing standing orders from the MSIC medical director (M.J.).
Participants were randomized to receive naloxone in 1 of 2 forms: (1) intranasal administration of naloxone hydrochloride 800 μg per 1 mL and intramuscular administration of placebo 1 mL, or (2) intramuscular administration of naloxone hydrochloride 800 μg per 1 mL and intranasal administration of placebo 1 mL. The 800-μg intramuscular dose has been used throughout the operation of the MSIC and is consistent with paramedic clinical practice guidelines in New South Wales,18 but the dose is higher than the 400 μg dose recommended by the World Health Organization.19 Two MSIC staff members attended the patient during treatment of opioid overdose, and a third attending staff member recorded study information on a data collection form.
For intranasal administration, the contents of the vial were drawn into 1 syringe, and the syringe was attached to a mucosal atomization device. Each nostril received 0.5 mL (400 μg), with rapid depression of the syringe to achieve adequate atomization. For intramuscular administration, following the standard practice, the full 1-mL dose was drawn into a single 3-mL syringe and injected into the deltoid muscle with a 23-gauge needle. The order of drug administration was altered approximately midway through the study. Initially, the intranasal route was first, followed by the intramuscular route, but the order was reversed for the second half of the study.
Supportive care or oxygenation was administered simultaneously in accordance with existing MSIC clinical protocols. Any client who failed to respond adequately (ie, GCS score remained <13, RR remained <10, or oxygen saturation remained <95%) after 10 minutes was given a second rescue dose of 800 μg of intramuscular naloxone hydrochloride. This dose was not subject to randomization.
Details of treatment methods are described in detail in the study protocol. Briefly, MSIC staff managed drug overdoses using existing clinical protocols. These protocols state that a client would receive airway management and oxygenation either via a mask or artificial ventilation (bagging) for 5 minutes and then would be assessed for the need for naloxone. If a consenting client’s response after 5 minutes was inadequate (oxygen saturation not maintained at ≥95% or with GCS score <13 or RR <10), the client was enrolled into the study, and trial drugs were administered by a registered nurse in accordance with existing standing orders from the MSIC medical director (M.J.).
Participants were randomized to receive naloxone in 1 of 2 forms: (1) intranasal administration of naloxone hydrochloride 800 μg per 1 mL and intramuscular administration of placebo 1 mL, or (2) intramuscular administration of naloxone hydrochloride 800 μg per 1 mL and intranasal administration of placebo 1 mL. The 800-μg intramuscular dose has been used throughout the operation of the MSIC and is consistent with paramedic clinical practice guidelines in New South Wales,18 but the dose is higher than the 400 μg dose recommended by the World Health Organization.19 Two MSIC staff members attended the patient during treatment of opioid overdose, and a third attending staff member recorded study information on a data collection form.
For intranasal administration, the contents of the vial were drawn into 1 syringe, and the syringe was attached to a mucosal atomization device. Each nostril received 0.5 mL (400 μg), with rapid depression of the syringe to achieve adequate atomization. For intramuscular administration, following the standard practice, the full 1-mL dose was drawn into a single 3-mL syringe and injected into the deltoid muscle with a 23-gauge needle. The order of drug administration was altered approximately midway through the study. Initially, the intranasal route was first, followed by the intramuscular route, but the order was reversed for the second half of the study.
Supportive care or oxygenation was administered simultaneously in accordance with existing MSIC clinical protocols. Any client who failed to respond adequately (ie, GCS score remained <13, RR remained <10, or oxygen saturation remained <95%) after 10 minutes was given a second rescue dose of 800 μg of intramuscular naloxone hydrochloride. This dose was not subject to randomization.
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