VOTIVE: Virginia Opioid Overdose Treatment InitiatVE

• Sponsor: Virginia Commonwealth University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03818399
• Collaborator: Indivior, PLC. (Other)
• Enrollment: 19
• Location: 1
• Arm: 1
• Actual Duration (Months): 25.7
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This is a Phase 3b, open-label study in patients that present to the ED for an opioid OD and receive treatment with an opioid antagonist. The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.

The study will assess subjects that receive acute administration of SUBOXONE sublingual film in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, compared to historical control data from electronic health records.

Condition or Disease	Intervention/Treatment	Phase
Opioid Use Disorder	Drug: SUBLOCADE	Phase 3

Detailed Description

The study will assess subjects that receive acute administration of SUBOXONE sublingual film in the Emergency Department (ED) followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, compared to historical control data from VCU electronic health records. The affiliated clinic will agree to see the subject on arrival at the clinic during normal clinic hours.

Patients presenting to the ED for an opioid overdose (OD) who received treatment with an opioid antagonist and are considered clinically stable and alert will be approached regarding interest in study participation. Written informed consent will only be obtained if the patient's judgement is intact as determined clinically by the investigator or a medically qualified sub-investigator or research nurse. This OD will be considered the index OD.

Subjects will be given the opportunity to participate in an optional pharmacogenetics (PGx) sub-study.

The subject will receive referral to an outpatient treatment clinic affiliated with the hospital system in which the ED resides.

Once subjects arrive at the treatment clinic, they will continue to receive SUBLOCADE for 6 months. All subjects will receive site standard psychosocial therapy at least weekly during the first 3 months of treatment, and twice monthly thereafter if clinically stable.

All subjects will complete an End of Treatment (EOT) / Early Termination (ET) visit 28 days after their last injection of SUBLOCADE. Within 3 months prior to or at the EOT visit, the investigator or a medically qualified sub-investigator will discuss the subject's available treatment options and arrange referral. All subjects will receive a safety follow-up telephone call, 30 days after their EOT/ET visit to assess AEs, SAEs, pregnancy status (if applicable) and concomitant medications. Subjects who decline to continue in medication assisted treatment (MAT) will receive monthly safety follow-up phone calls for an additional 5 months (6 months total) to assess SAEs, pregnancy status (if applicable) and concomitant medications.

Study Design

• Study Type: Interventional
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.The study is designed to determine effect of SUBLOCADE on repeat overdose and death compared to historical control data.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Virginia Opioid Overdose Treatment InitiatVE
• Actual Study Start Date: Jan 4, 2019
• Actual Primary Completion Date: Feb 24, 2021
• Actual Study Completion Date: Feb 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: overdose patients subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment.	Drug: SUBLOCADE; SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.

Outcome Measures

Primary Outcome Measures

1. Number of Repeat OD or Opioid-related Death [6 months]

   Repeat OD or opioid-related death will be measured from electronic medical records and state death registries

Secondary Outcome Measures

1. Treatment Engagement [3 and 6 months]

   Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.

Other Outcome Measures

1. Opioid Craving [6 months]

   Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)

2. Illicit Opioid Use [6 months]

   Illicit opioid use as measured by urine drug screen (UDS) results.

3. Genetic Predictors of Treatment Response [6 months]

   Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects

4. Healthcare Resource Utilization [6 months]

   Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls

5. Treatment Effectiveness and Employment [6 months]

   Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)

6. Medication Satisfaction [6 months]

   measured by the Medication Satisfaction Questionnaire (MSQ)

7. Employment, Presentism and Absenteeism [6 months]

   assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed the informed consent form (ICF) and have the ability to comply with the requirements and restrictions listed therein.

• Age: ≥ 18 years at time of executing the ICF.

• Currently meets DSM-5 criteria for moderate to severe opioid use disorder.

• Must have Clinical Opioid Withdrawal Scale (COWS) score of >8 to be eligible for SUBOXONE dose.

• Is clinically stable (respiratory rate [RR] ≥ 12, pulse oximetry > 95%, Glasgow Coma Scale [GCS] score of 15) and suitable for the trial in investigator or designee's judgement.

• Agrees not to take any buprenorphine products other than those administered during the current study throughout participation in the study.

• Negative urine pregnancy test for females.

• Vital signs (blood pressure, heart rate, temperature) considered within normal limits or non-clinically significant elevation, as assessed by treating physician.

Exclusion Criteria:

• Current diagnosis, other than opioid use disorder, requiring chronic opioid treatment.

• Active suicidal ideation in opinion of investigator or designee.

• Female subject that is lactating, pregnant or planning to become pregnant during their participation in the study.

• Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to provide written informed consent, signs of opioid toxicity more than 2 hours from naloxone administration or subjects with evidence of pulmonary edema.

• Known allergy or hypersensitivity to SUBOXONE.

• Any condition that, in the opinion of the investigator would interfere with interpretation of subject safety or study results.

• Currently receiving medication assisted treatment (MAT) for opioid use disorder (OUD) (e.g. methadone, buprenorphine) or received MAT as a treatment for OUD within 30 days prior to consent.

• Concurrent treatment with another investigational agent.

• Concurrent enrolment in another clinical study, or observational study that includes MAT.

• Treatment for opioid use disorder required by court order.

• Current or pending incarceration/ legal action that could affect participation or compliance in the study.

• Subjects who are unable, in the opinion of the investigator, to comply fully with the study requirements.

• Less than 48-72 hours since last use of long acting opioids (e.g., methadone), by self-report.

• Current intoxication with benzodiazepines or alcohol.

• Meet current DSM-5 diagnosis for severe Benzodiazepine or Alcohol Use Disorder, or endorse benzodiazepine or alcohol withdrawal symptoms.

• Current illicit opioid users who endorse regular use of long acting opioids (e.g. methadone).

• Total bilirubin ≥ 1.5x the upper limit of normal (ULN), alanine aminotransferase (ALT) ≥3xULN, aspartate aminotransferase (AST) ≥ 3xULN, serum creatinine > 2xULN, international normalized ratio (INR) >1.5xULN

• Patients with a history of Long QT Syndrome or an immediate family member with this condition or those taking Class lA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class Ill antiarrhythmic medications (e.g., sotalol, amiodarone, or other mediations that prolong the QT interval.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Virginia Commonwealth University	Richmond	Virginia	United States	23298

Sponsors and Collaborators

• Virginia Commonwealth University
• Indivior, PLC.

Investigators

• Principal Investigator: Frederick G Moeller, MD, Virginia Commonwealth University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 23, 2020

More Information

Publications

None provided.

• Responsible Party: Virginia Commonwealth University
• ClinicalTrials.gov Identifier: NCT03818399
• Other Study ID Numbers: HM20015109
• First Posted: Jan 28, 2019
• Last Update Posted: May 5, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Opioid-Related Disorders; Opiate Overdose; Buprenorphine

Study Results

Participant Flow

Arm/Group Title	Overdose Patients
Arm/Group Description	subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment. SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
Period Title: Overall Study
STARTED	19
COMPLETED	5
NOT COMPLETED	14

Baseline Characteristics

Arm/Group Title	Overdose Patients
Arm/Group Description	subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment. SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
Overall Participants	19
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.4 (12.1)
Sex: Female, Male (Count of Participants)
Female	2 10.5%
Male	17 89.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	17 89.5%
Unknown or Not Reported	2 10.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	18 94.7%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	1 5.3%
Region of Enrollment (participants) [Number]
United States	19 100%

Outcome Measures

1. Primary Outcome

Title	Number of Repeat OD or Opioid-related Death
Description	Repeat OD or opioid-related death will be measured from electronic medical records and state death registries
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Because repeat OD or opioid-related death is measured from electronic medical records and state death registries, data was collected on all participants even if they did not complete the study

Arm/Group Title	Overdose Patients
Arm/Group Description	subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment. SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
Measure Participants	19
Prevalence of repeat opioid-related overdose	0 0%
Prevalence opioid-related death	0 0%

2. Secondary Outcome

Title	Treatment Engagement
Description	Treatment engagement as measured by number of outpatient clinic visits (attendance), receipt of SUBLOCADE injections (buprenorphine treatment) at 3 and 6 months.
Time Frame	3 and 6 months

Outcome Measure Data

Analysis Population Description

An intent to treat model was used so data from all participants, even those who did not complete, was analyzed

Arm/Group Title	Overdose Patients
Arm/Group Description	subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment. SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
Measure Participants	19
3 months	8.1 (7.72)
6 months	13.3 (9.8)

3. Other Pre-specified Outcome

Title	Opioid Craving
Description	Opioid craving in subjects as measured by Craving Visual Analog Scale (VAS), a 3-item scale in which individuals rate their cravings for opioids on a scale from 0 (NOT AT ALL) to 10 (EXTREMELY)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Illicit Opioid Use
Description	Illicit opioid use as measured by urine drug screen (UDS) results.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Genetic Predictors of Treatment Response
Description	Number of participants with mu opioid receptor polymorphisms associated with repeat overdose and death history of OD in subjects
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Healthcare Resource Utilization
Description	Healthcare resource utilization (measured by number of outpatient clinic and emergency department visits, and number of inpatient admissions) as compared to the historical controls
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Treatment Effectiveness and Employment
Description	Treatment effectiveness as measured by Treatment Effectiveness Assessment (TEA)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Medication Satisfaction
Description	measured by the Medication Satisfaction Questionnaire (MSQ)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Employment, Presentism and Absenteeism
Description	assessed by the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	6 months
Arm/Group Title	Overdose Patients
Arm/Group Description	subjects that receive acute administration of SUBOXONE sublingual film in the ED followed by SUBLOCADE administration in the ED and referral to an affiliated outpatient treatment clinic, and receive monthly SUBLOCADE injections for 6 months in the context of outpatient treatment. SUBLOCADE: SUBLOCADE (buprenorphine extended-release) injection is a colorless to amber sterile solution for SC injection designed to deliver buprenorphine at doses of 100 mg or 300 mg at a controlled rate over a one-month period.
All Cause Mortality
	Overdose Patients
	Affected / at Risk (%)	# Events
Total	0/19 (0%)
Serious Adverse Events
	Overdose Patients
	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)
Infections and infestations
Osteomyelitis	1/19 (5.3%)	1
Psychiatric disorders
Inpatient psychiatric treatment for schizoaffective disorder	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	Overdose Patients
	Affected / at Risk (%)	# Events
Total	11/19 (57.9%)
Cardiac disorders
Heart flutter	1/19 (5.3%)	1
Lower extremity edema	1/19 (5.3%)	1
Eye disorders
Eye pain	1/19 (5.3%)	1
Gastrointestinal disorders
Constipation	4/19 (21.1%)	6
Nausea	1/19 (5.3%)	1
General disorders
Reduced appetite	1/19 (5.3%)	1
Sedation	1/19 (5.3%)	1
Withdrawal symptoms	1/19 (5.3%)	1
Musculoskeletal and connective tissue disorders
Leg muscle cramps after fall	1/19 (5.3%)	1
Acute neck strain	1/19 (5.3%)	1
Nervous system disorders
Drowsiness	1/19 (5.3%)	1
Injection site pain	3/19 (15.8%)	5
Acute back pain from moving	1/19 (5.3%)	1
Chronic back pain	1/19 (5.3%)	1
Chronic neck pain associated with arthritis	1/19 (5.3%)	1
Acute left knee pain with comorbid arthritis	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
Inflammation at injection site	1/19 (5.3%)	1
Lip abscess	1/19 (5.3%)	1
Maculopapular rash	1/19 (5.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.