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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new strategy to improve naloxone distribution through syringe service programs (SSPs). Researchers aim to determine if a special coaching method, SAIA-N (Systems Analysis and Improvement Approach for Naloxone), can help these programs distribute more naloxone compared to their usual methods and assess its cost-effectiveness. SSPs in California that already provide naloxone qualify for this study, provided they have not participated in the SAIA-N pilot before. As an unphased trial, this study presents a unique opportunity to contribute to innovative strategies that could enhance naloxone distribution and potentially save lives.

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 prior data suggests that the Systems Analysis and Improvement Approach for Naloxone (SAIA-N) is safe for improving naloxone distribution?

Research has shown that naloxone is generally safe for use. Widely used to reverse opioid overdoses, naloxone is well-tolerated. The Systems Analysis and Improvement Approach for Naloxone (SAIA-N) is not a drug but a method to enhance naloxone distribution. Therefore, SAIA-N does not carry the safety risks associated with new drugs. Instead, it aids organizations in distributing naloxone more effectively. No reports have indicated problems related to SAIA-N. Naloxone itself maintains a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Improved Naloxone Access trial because it explores how to enhance naloxone distribution within syringe service programs (SSPs), beyond just providing naloxone itself. This trial is testing the Systems Analysis and Improvement Approach for Naloxone (SAIA-N), which is an innovative method that involves assigning coaches to help SSP staff identify and overcome barriers to effective naloxone distribution. Unlike the usual approach, which doesn’t offer additional support, SAIA-N aims to optimize existing naloxone distribution efforts by engaging staff in continuous improvement cycles. This method could potentially lead to more efficient and widespread access to naloxone, a life-saving medication for opioid overdoses.

What evidence suggests that this trial's strategies could be effective for improving naloxone distribution?

Research shows that the Systems Analysis and Improvement Approach for Naloxone (SAIA-N), which participants in this trial may experience, might help syringe service programs distribute more naloxone. This method employs a trained coach to assist these programs in identifying and resolving barriers to naloxone distribution, a life-saving drug during opioid overdoses. Similar strategies have proven effective in the past for improving naloxone distribution. The aim is to increase naloxone availability, especially in high-need areas. While specific data on SAIA-N is still being collected, early indications suggest it might outperform usual methods, which are also under study in this trial. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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

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

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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 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]

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]

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]

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]

Citations

1. implementationscience.biomedcentral.com implementationscience.biomedcentral.com/articles/10.1186/s13012-023-01288-x

study protocol of a randomized controlled trial This randomized controlled trial will test SAIA-Naloxone's ability to improve naloxone distribution in general and among BIPOC specifically.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37537665/

study protocol of a randomized controlled trial - PubMed - NIH Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05886712?term=Naloxone&rank=10

Improving Access to Naloxone to Prevent Opioid Overdose ... The goal of this clinical trial is to compare the effectiveness of a multi-faceted implementation strategy, the Systems Analysis and Improvement Approach for ...

4. saia-strategy.com saia-strategy.com/saia-naloxone

Naloxone — SAIA Optimizing naloxone distribution to prevent opioid overdose fatalities: results from piloting the Systems Analysis and Improvement Approach within syringe ...

5. researchgate.net researchgate.net/publication/372888072_Systems_analysis_and_improvement_approach_to_improve_naloxone_distribution_within_syringe_service_programs_study_protocol_of_a_randomized_controlled_trial

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

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10035142/

Optimizing naloxone distribution to prevent opioid ... The objective of this study was to pilot test a multi-component implementation strategy—the systems analysis and improvement approach for ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05886712

Improving Access to Naloxone to Prevent Opioid Overdose ... The goal of this clinical trial is to compare the effectiveness of a multi-faceted implementation strategy, the Systems Analysis and Improvement Approach ...