Improved Naloxone Access for Opioid Overdose

(SAIA-N Trial)

Overseen By Christopher F Akiba, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: RTI International

Disqualifiers: Participated in SAIA-N pilot

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12 months

31 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to compare the effectiveness of a multi-faceted implementation strategy, the Systems Analysis and Improvement Approach for Naloxone (SAIA-N), in syringe service programs (SSPs). The main questions it aims to answer are: * Does SAIA-N improve naloxone distribution (number of doses, number of people receiving naloxone) compared to implementation as usual (IAU)? * What are the costs associated with SAIA-N and how cost-effective is the strategy? SSPs randomized to the SAIA-N arm will participate in the strategy for a period of 12-months during which they will meet 1-2 times each month with a SAIA coach who will assist the SSP in optimizing their naloxone distribution. Researchers will compare SAIA-N to IAU to see if naloxone distribution and costs and cost-effectiveness differ by group.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the drug Naloxone for opioid overdose?

Research shows that naloxone, an opioid antagonist (a drug that blocks the effects of opioids), can effectively reverse opioid overdoses and prevent deaths when administered promptly. Studies have demonstrated that increasing access to naloxone through various delivery methods, such as auto-injectors and intranasal systems, can help save lives during opioid overdose emergencies. ^{1 2 3 4 5}

Is naloxone generally safe for human use?

There is no relevant safety information about naloxone in the provided research articles. ^{6 7 8 9 10}

How is the drug naloxone used in the SAIA-Naloxone approach different from other treatments for opioid overdose?

The SAIA-Naloxone approach is unique because it focuses on improving naloxone distribution through syringe service programs, specifically targeting barriers to access among marginalized communities, such as Black, Indigenous, and people of color (BIPOC). This strategy aims to enhance the availability and timely administration of naloxone, an opioid antagonist that reverses overdoses, by addressing systemic issues in distribution. ^{2 3 4 11 12}

Eligibility Criteria

This trial is for syringe service programs (SSPs) in California that are authorized by CDPH and have recently distributed naloxone. It's designed to improve how naloxone is given out to prevent opioid overdose deaths, focusing on reaching diverse populations including Black, Indigenous, and People of Color.

Inclusion Criteria

SSP is located and operates in California

SSP is authorized by CDPH

SSP has distributed naloxone to participants in the past 30 days

Exclusion Criteria

SSPs who participated in the SAIA-Naloxone pilot study (n = 2)

I am part of an SSP that does not distribute naloxone.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 months

Monthly data collection

Treatment

SSPs participate in the SAIA-N strategy with coaching sessions to optimize naloxone distribution

12 months

1-2 visits per month with SAIA coach

Sustainment

Assessment of naloxone distribution sustainment post-intervention

6 months

Monthly data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• Naloxone
• Systems Analysis and Improvement Approach for Naloxone (SAIA-N)
• Usual intervention

Trial Overview The study tests a new strategy called SAIA-N against the usual way SSPs give out naloxone. SAIA-N involves regular meetings with a coach to help optimize distribution over 12 months. The effectiveness will be measured by the number of doses and people reached, especially among BIPOC communities.

Participant Groups

Group I: SAIA-Naloxone Experimental Treatment 1 Intervention

SAIA-Naloxone is an intervention that facilitates an organizational SSP level analysis of naloxone delivery by assigning a trained SAIA-Naloxone coach to apply tools and techniques and engage staff to define barriers, identify solutions, and evaluate their success in cycles until achieving desired change regarding naloxone distribution. Coaches will meet with SSPs twice per month for the first 3 months and once per month for the remaining 9 months during the 12-month intervention period.

Group II: Implementation as Usual Experimental Treatment 1 Intervention

SSPs randomized to the IAU arm will not receive support to improve naloxone distribution. SSPs in California have already adopted naloxone distribution. The investigators are therefore testing the ability of SAIA-Naloxone to optimize naloxone distribution within SSPs. Accordingly, IAU is characterized by the absence of SAIA-Naloxone with the goal of comparing whether SAIA-Naloxone improves SSPs' Naloxone distribution.

Naloxone is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Naloxone for:

• Opioid overdose reversal

Approved in European Union as Naloxone for:

• Opioid overdose reversal

Approved in Canada as Naloxone for:

• Opioid overdose reversal

Who Is Running the Clinical Trial?

RTI International

Lead Sponsor

Trials

201

Recruited

942,000+

Heluna Health

Collaborator

Trials

1

Recruited

30+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Findings from Research

In a study involving 42 healthy participants, the naloxone auto-injector (NAI) was significantly more effective than the intranasal delivery system (NXN) for administering naloxone during a simulated opioid overdose, with 90.5% success for NAI compared to 0% for NXN before training.

After training, 100% of participants successfully used NAI, while only 57.1% could use NXN, highlighting that NAI is easier to use and requires less training for effective administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. Edwards, ET., Edwards, ES., Davis, E., et al.[2020]

The SAIA-Naloxone implementation strategy significantly improved naloxone distribution in syringe service programs, with a 37% increase in participants receiving naloxone and a 105% increase in doses distributed weekly during the 6-month pilot study involving 11,107 doses and 6,071 participants.

These results suggest that systematic improvements in data collection and participant identification can enhance naloxone access, highlighting the potential for SAIA-Naloxone to be tested in larger trials to combat the opioid overdose crisis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing naloxone distribution to prevent opioid overdose fatalities: results from piloting the Systems Analysis and Improvement Approach within syringe service programs. Patel, SV., Wenger, LD., Kral, AH., et al.[2023]

A study involving 122 HIV clinicians showed that on-site peer-to-peer training significantly increased their likelihood to prescribe naloxone, with an odds ratio of 4.1, indicating a strong positive change in attitudes towards naloxone prescribing.

The intervention led to a notable increase in the number of clinicians prescribing naloxone across 18 out of 22 sites, with a 2.9 times higher incidence rate of naloxone prescriptions post-intervention, although the overall percentage of HIV patients receiving naloxone only modestly increased from 0.97% to 1.6%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescribe to Save Lives: An Intervention to Increase Naloxone Prescribing Among HIV Clinicians. Friedmann, PD., Jawa, R., Wilson, D., et al.[2023]

A randomized controlled trial involving 32 syringe service programs (SSPs) in California will test the SAIA-Naloxone strategy, which aims to improve naloxone distribution, particularly among Black, Indigenous, and people of color (BIPOC) populations, who face significant disparities in access.

The SAIA-Naloxone approach involves a 12-month collaboration with trained facilitators to identify and address barriers to naloxone access, potentially providing a sustainable solution to combat the rising opioid overdose mortality rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial. Akiba, CF., Patel, SV., Wenger, LD., et al.[2023]

Intranasal naloxone is considered the best option for opioid reversal in prehospital settings due to its balance of cost, effectiveness, and safety for the administrator, based on an analysis of 8 studies.

There is no clear consensus on the best route of naloxone administration, as various methods (intramuscular, intranasal, intravenous, and subcutaneous) were evaluated but showed differing results in terms of administration time and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Naloxone Administration for Opioid Overdose Reversal in the Prehospital Setting: Implications for Pharmacists. Weaver, L., Palombi, L., Bastianelli, KMS.[2018]

In a study involving New Zealand white rabbits, two different routes of antivenom administration (standard IV vs. regional administration below a tourniquet) showed no significant differences in limiting muscle necrosis after rattlesnake venom poisoning.

The pilot study concluded that the antivenom (ACP) administered in the doses and methods tested did not effectively reduce muscle damage, as indicated by serum CPK levels, radionucleotide uptake, and muscle necrosis grading.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regional vs systemic antivenom administration in the treatment of snake venom poisoning in a rabbit model: a pilot study. Norris, RL., Dery, R., Johnson, C., et al.[2019]

In a study of 73 patients with rattlesnake bites, the administration of polyvalent antivenin was found to be safe, with no deaths, amputations, or permanent disabilities reported among those treated.

Acute side effects occurred in 18% of patients, primarily manifesting as urticaria, indicating that while hypersensitivity reactions can happen, they are generally mild and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does the aggressive use of polyvalent antivenin for rattlesnake bites result in serious acute side effects? Offerman, SR., Smith, TS., Derlet, RW.[2019]

The study determined the toxicity levels of elapid and viperid snake venoms in mice and rats, providing insights into lethal venom concentrations that could inform human snake bite cases.

High voltage-low current electric shock treatment was found to postpone death in mice after elapid envenomation by 60-90 minutes, suggesting a potential method for neutralizing venom effects, although it did not have the same effect for viperid envenomation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities, LD50 prediction and in vivo neutralisation of some elapid and viperid venoms. Khare, AD., Khole, V., Gade, PR.[2017]

In a study with rhesus monkeys, doses of Vipera berus venom as low as 1 mg/kg caused severe systemic and local effects, while higher doses (2-4 mg/kg) resulted in death from shock, highlighting the venom's potency.

Zagreb antivenom was effective in saving monkeys when administered within 4 hours of venom injection, especially at higher doses, suggesting its potential use in treating severe adder-bite poisoning to reduce both mortality and local tissue damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Zagreb antivenom against envenoming by the adder, Vipera berus. Theakston, RD., Reid, HA.[2019]

In a study of 123 patients with rattlesnake envenomations, those treated with the equine-derived antivenom F (ab')2 AV were less likely to develop late coagulopathy compared to those treated with the ovine-derived Fab AV, indicating a potential safety advantage for F (ab')2 AV.

Patients receiving F (ab')2 AV were also more likely to require additional doses of antivenom, suggesting that while both treatments are effective, the dosing strategy may differ between the two antivenoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019. Wilson, BZ., Bahadir, A., Andrews, M., et al.[2022]

Over 1,000 injection drug users were trained in naloxone administration through the SKOOP program in New York City, highlighting the effectiveness of training in preventing fatal heroin overdoses.

The program faced several challenges, including political issues and recruitment difficulties, but emphasized the importance of flexibility and participant feedback in successfully implementing naloxone distribution initiatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overdose prevention for injection drug users: lessons learned from naloxone training and distribution programs in New York City. Piper, TM., Rudenstine, S., Stancliff, S., et al.[2018]

In a study of 2152 patients from community pharmacies in Maine and New Hampshire, 21.7% of naloxone prescriptions were never dispensed, indicating a significant issue with primary medication nonadherence (PMN).

Factors contributing to PMN included urban location, payment method (higher rates among cash and private insurance), and the presence of concomitant opioid prescriptions, suggesting that addressing financial barriers and optimizing naloxone access strategies could improve adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of naloxone access and primary medication nonadherence in a community pharmacy setting. Connolly, E., McCall, KL., Couture, S., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Optimizing naloxone distribution to prevent opioid overdose fatalities: results from piloting the Systems Analysis and Improvement Approach within syringe service programs. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Prescribe to Save Lives: An Intervention to Increase Naloxone Prescribing Among HIV Clinicians. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Naloxone Administration for Opioid Overdose Reversal in the Prehospital Setting: Implications for Pharmacists. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Regional vs systemic antivenom administration in the treatment of snake venom poisoning in a rabbit model: a pilot study. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Does the aggressive use of polyvalent antivenin for rattlesnake bites result in serious acute side effects? [2019]

8. India pubmed.ncbi.nlm.nih.gov

Toxicities, LD50 prediction and in vivo neutralisation of some elapid and viperid venoms. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Effectiveness of Zagreb antivenom against envenoming by the adder, Vipera berus. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Initial Experience with F(ab')2 Antivenom Compared with Fab Antivenom for Rattlesnake Envenomations Reported to a single poison center during 2019. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Overdose prevention for injection drug users: lessons learned from naloxone training and distribution programs in New York City. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Analysis of naloxone access and primary medication nonadherence in a community pharmacy setting. [2022]