Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03908437 |
| Other study ID # |
R01CE003049 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
July 15, 2019 |
| Est. completion date |
June 30, 2023 |
Study information
| Verified date |
August 2023 |
| Source |
University of Pennsylvania |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The proposed research will evaluate the ability of a mobile, rapid induction procedure to
engage individuals in ongoing medication assisted treatment. A total of 250 untreated
individuals meeting criteria for opioid use disorder and at high risk of opioid overdose will
be enrolled in the study. Recruitment will take place in two targeted neighborhoods of
Philadelphia (Kensington and South Philadelphia) with a high prevalence of fatal and
non-fatal opioid overdose. A total of 250 participants will be engaged in the research.
Following informed consent and determination of eligibility, 125 individuals will be enrolled
as they engage with the mobile, rapid induction team and 125 individuals will be enrolled as
they seek treatment from the CRC Episcopal Hospital (serving Kensington area) or BAC/CRC Hall
Mercer Community Mental Health (serving South Philadelphia). The intervention group will
receive four weeks of treatment with buprenorphine /naloxone and support for treatment
engagement provided by a case manager and a peer recovery specialist. All participants will
be assessed at baseline and then 1- and 6-month following enrollment. The primary endpoint
for the study is continued enrollment in medication-assisted treatment at 6-month
post-enrollment.
The proposed research will evaluate the ability of a mobile, rapid induction procedure to
engage individuals in ongoing medication assisted treatment.
The specific aims are:
- Aim 1: To evaluate the impact of the mobile, transitional MAT intervention on its
ability to engage participants in targeted, existing MAT treatment slots at 1- and
6-month post-enrollment.
- Aim 2: To evaluate the impact of the mobile intervention on subsequent drug use and
overdoses at 6-month post-enrollment.
- Aim 3: To assess the acceptability and costs of the intervention. The program and
patient costs of delivering and participating in the intervention will be documented.
Description:
1. Study Objectives Aim 1: To evaluate the impact of the mobile, transitional MAT
intervention on its ability to engage participants in targeted, existing MAT treatment
slots at 1- and 6-month post-enrollment.
Aim 2: To evaluate the impact of the mobile intervention on subsequent drug use and
overdoses at 6-month post-enrollment.
Aim 3: To assess the acceptability and costs of the intervention. The program and
patient costs of delivering and participating in the intervention will be documented.
Study participants who will receive buprenorphine/naloxone will be provided with
information, counseling, and support for selection of ongoing treatment options
including methadone maintenance (MMT), extended-release naltrexone (XR-NTX), or
continued treatment with buprenorphine/naloxone.
2. Study design Duration of Study Participation The duration of study participation
including screening/baseline assessments to follow-up will be 6 months.
Total Number of Subjects A total of 250 participants will be engaged in the research at
the time they seek treatment: 125 individuals will be enrolled as they engage with the
mobile, rapid induction team and 125 individuals will be enrolled as they seek treatment
from the BAC/CRC (treatment as usual).
Subject Recruitment The recruitment of participants for this study will be accomplished
using a community awareness campaign involving street outreach, targeted social media,
and local advertisement. This campaign will begin one month before activation of the
rapid induction intervention. During this time, the mobile assessment team will begin to
be present in the designated location where the Mobile Clinical Trials Unit (MCTU) will
be parked.
Participant Education and the Informed Consent Process Potential participants who
express interest in initiating treatment will be engaged in a structured approach to
education about the study and its procedures. The information delivered at this point
will be supportive and motivational and describe study participation as an opportunity
to consider options for treatment. It will also be explained that their participation
can contribute to a better understanding of the most effective ways to assist
individuals who want to begin treatment. Staff will make it clear that even if they do
not become engaged in treatment, their experiences are important and their contributions
to the research will be valuable. This discussion will offer potential participants a
chance to ask questions and receive prepared materials explaining the study and the
requirements for participation.
Those who appear to be eligible and express interest will begin the informed consent
process to allow for screening. The informed consent process will give the participant
an accurate understanding of the research procedures and make it clear that
participation is voluntary. The informed consent document will be read and reviewed with
the participant. The consent form includes clear language with special attention to the
provision of permissions to contact the participant and individuals they identify as
acceptable contacts if the research assistants are unable to make direct contact with
the participant for the 1- and 6-month assessments.
Screening assessments For those who remain interested following discussions and appear
to meet eligibility criteria, the consent form will be signed and the screening visit
will be conducted. This visit will include completion of assessments to confirm
inclusion and exclusion criteria. The Nurse Practitioner will complete a medical
history, a physical exam, a rapid blood test for HIV, a pregnancy test for women, and
collect 10ml of blood for liver function tests. Research staff will complete baseline
assessments. Those who are not eligible will receive a listing of treatment providers
and encouraged to make contact for help with their substance use problems. For those who
appear eligible following the screening visit, an appointment for initiating the
intervention will be scheduled within 1 or 2 days.
Study Measures All interviews will be administered by experienced research assistants
trained in the administration of the proposed assessments. Following confirmation of
eligibility, the mobile research assistants will complete the baseline assessment
(described below). The participant assessments in this research will be sharply focused
on the valid and reliable measurement of its primary endpoints i.e. ongoing treatment
engagement will be the primary endpoint on which the study is powered. The two groups
will be compared with respect to the rate of continued opioid use and subsequent
overdoses. All assessments will be completed by trained research staff (not clinicians)
at baseline, and again at 1- and 6-month post-enrollment. A follow-up rates of 95% and
90% at Month 1 and 6, respectively is anticipated. The assessments will take
approximately 45 minutes to complete.
- Physical history and examination including a blood test to evaluate the liver
function.
- Locator Data Collection: A detailed contact sheet (Locator Form) will be completed
for all subjects as part of the baseline assessment. The form will be updated at
each scheduled assessment visit.
- DSM-5 Substance Use Disorder Checklist: This form is a listing of the eleven DSM-5
criteria for substance use disorder. Opioids, cocaine, and alcohol use disorders
will be screened for confirmation of inclusion and exclusion criteria. A score of
4-6 is considered moderate severity and from 7-11 is considered severe substance
use disorder. An opioid use disorder score of 4 or greater will be required for
study eligibility. Alcohol use disorder and benzodiazepine scores of 4 or greater
will be exclusionary.
- A study specific questionnaire that gathers socio-demographic information (e.g.
age, gender, race and ethnic identity, marital status, sexual orientation,
educational level, employment status, income and income sources) and descriptive
information about the subject's living situation and housing stability, history of
involvement with the criminal justice system, drug use, and drug treatment history.
o Addiction Severity Index (ASI) sections for Drugs and Alcohol and Medical Status:
The ASI is a structured interview developed to assess the range of problems seen in
drug users. The ASI produces severity ratings and composite scores in each of seven
areas, and each type score has been assessed with regard to validity and
reliability. Severity ratings and composite scores have demonstrated high levels of
inter-rater, test-retest, and concurrent reliability (Cacciola et al., 2008;
McLellan, Cacciola, Alterman, Rikoon, & Carise, 2006; McLellan et al., 1992). The
Medical and the Drug and Alcohol sections will be administered at baseline, 1- and
6-month follow-ups.
- Patient Health Questionnaire (PHQ-9): Given the important role of depression in
accessing and adhering to treatments for substance use disorder and other chronic
medical problems (Mahajan, Avasthi, Grover, & Chawla, 2014; Tavakkoli, Ferrando,
Rabkin, Marks, & Talal, 2013), the severity of depression using the 9-item Patient
Health Questionnaire (PHQ-9) will be assessed. This brief assessment asks
participants to indicate the frequency of occurrence of each of the nine DSM-IV
diagnostic criteria for depression during the previous two weeks. This instrument
has been widely used in clinical research and has strong psychometric properties.
The PHQ-9 will be completed at baseline and month-1 and -6.
- Urine drug screen using the CLIA waived® ACON Dip-and-Read 8-panel test for THC,
cocaine, opiates, amphetamines, PCP, methamphetamine, benzodiazepines,
barbiturates, and buprenorphine. The urine sample will be provided using standard
procedures with temperature monitoring to preclude tampering and dilution.
- HIV testing: Chembio SURE CHECK HIV 1/2® rapid-HIV test kits will be used to detect
antibodies. These FDA approved and CLIA Waived kits produce results in 15 minutes
from a blood drop. For those who test antibody positive, additional blood will be
drawn for confirmatory testing via RNA viral load assay. Approximately 10% of
participants will test positive for HIV.
- Economic evaluation: The cost-effectiveness of the intervention will be performed
using data collected with questionnaires widely used for cost-effectiveness
analyses, the Drug Abuse Treatment Cost Analysis Program (DATCAP) and Non-Medical
and Other Services Form (NSMOS). The DATCAP is a reliable instrument widely used by
substance abuse treatment programs for the collection and organization of
programmatic costs (French et al. 1997). The NSMOS is a questionnaire adapted from
the Treatment Services Review (McLellan et al., 1992; Cacciola et al., 2008 ) for
individuals receiving substance abuse treatment.
Overview of Interventions Rapid Induction Intervention (RI) The rapid induction
intervention will be delivered by the project's mobile team led by a nurse practitioner
supported by a certified peer recovery specialist (CPRS), and a case manager (CM). Team
members will work closely with each other and coordinate screening and treatment
initiation, medication adherence monitoring, and assessment and linkage to ongoing MAT.
Two half-time research assistants (RA) will participate as team members but will have
intervention responsibilities. The RAs will assist with the community awareness campaign
and recruitment and will conduct all assessments for the project. The mobile team will
be based at Prevention Point Philadelphia and will receive clinical supervision from the
mobile team's buprenorphine physician.
Induction: Once eligibility has been determined, the NP will begin preparing the
participant for induction, following the buprenorphine/naloxone induction protocol used
by D'Onofrio et al., 2015.
Medication Assisted Treatment (MAT) engagement during the month of intervention will be
facilitated by the Peer Recovery Specialist (PRS). The purpose of a PRS is to support
the participant in their recovery process. In addition, the project will provide
intensive training and ongoing consultation on MAT. The PRS hired for this study will
also receive intensive training focused on addiction as a chronic medical condition,
motivational enhancement strategies and facilitating short-term behavioral contracts.
The PRS will meet with the participant a minimum of 3 times per week and be available
for telephone counseling and support throughout the one-month intervention period.
The mobile team's Case Management (CM) function will be performed by a master's level
social worker. The CM will have primary responsibility for identifying the treatment
program that best meets the needs of the participant. The CM effort will be sharply
focused on identifying and removing barriers to MAT treatment engagement. This will
include completing medication authorization forms and insurance enrollment if necessary,
and then making referrals to additional supports, including mental health treatment,
housing, medical, legal support, and peer-based recovery supports in the community. The
CM will work collaboratively with participants to remove barriers to care and to enhance
program outcomes and to provide psychosocial support.
The mobile team will insure that there is a clear plan for rapid engagement with ongoing
treatment as soon as possible. Buprenorphine/naloxone will be provided during the time
of transition to their long-term provider for up to 1 month. Telephone support will be
available should participants have questions or need assistance and the mobile team will
also have daily contact with participants until they complete contact with their ongoing
provider.
Comparison group - Treatment as usual During the same period of time, participants will
also be recruited at the City of Philadelphia Behavioral Health System Behavioral
Assessment Centers (BAC) and Crisis Response Centers (CRC) located at Episcopal Hospital
serving Kensington area and Hall Mercer BAC/CRC (a University of Pennsylvania program)
serving South Philadelphia area. Two research assistants from the TRI-PHMC will enroll
and follow-up 125 participants at BAC/ CRC. The participants will complete the same
assessments at baseline, 1- and 6-month follow-up. Authorization for the Philadelphia
Department of Public Health to look shared information about their subsequent use of
health department services (CARES database,
http://www.phila.gov/hhs/data/Pages/Cares.aspx) will also be requested in the consent
form. Research staff will only conduct assessments. Treatment engagement services will
be provided by the staff of the BAC/CRC as usual.
Subject Withdrawal Participants may choose to withdraw from the study at any time. They
do this by providing verbal or written communication to this effect. Withdrawal from the
study will not impact access to care. The Principal Investigator may withdraw subjects
for reasons related to safety or for administrative reasons. It will be documented
whether or not each subject completes the study. Subjects who do not complete the
intervention will continue to be contacted to complete follow-up visits (Month 1 and 6)
to collect final evaluations and to assess adverse events.
3. Statistical Plan 3.1. Data Quality Trained staff will review all forms prior to the
completion of the study visit in an effort to minimize problems associated with missing
values and incorrect skip patterns. All assessments will be recorded on final version of
the electronic Case Reporting Forms (eCRFs). eCRFs will also be developed to capture the
results of all biological assessments. All eCRFs will be completed using only
participant identifying numbers and will not include names, addresses, or other data
that could possibly be used to disclose the identity of the participant. Research staff
will be responsible for entering all data into the secure web-based developed on REDCap
(Research Electronic Data Capture). REDCap is designed to comply with HIPAA regulations.
Data will be input with secure web authentication, data logging, and Secure Sockets
Layer (SSL) encryption. REDCap allows multisite access. It allows real-time data entry
validation (e.g. for data types and range checks), audit trails, and the ability to set
up a calendar to schedule and track critical study events such as participant visits.
The data quality control process associated with data processing will consist of the
following stages: potential subject pre-screening for eligibility, registration, subject
eligibility confirmation, first data entry, second data entry in the form of 100%
interactive verification, data validation, and data auditing. A random 5% of the
questionnaires in each wave of data collection (i.e., baseline, 1- and 6-month) will be
subjected to database auditing throughout the trial. This data quality control process
ensures that all stages of the data handling process will be subjected to data quality
control.
3.2. Data analyses Propensity score model to account for non-randomized allocation: The
participants are not randomly assigned to the mobile rapid induction intervention and
BAC/CRC groups, so it is possible that there will be confounding of the group effect
with the effects of characteristics of the participants. Propensity score approach
(Rosenbaum 2002, Rothman, Greenland et al. 2008) will be used to account for this. A
broad range of baseline variables will be entered as covariates in a logistic regression
model predicting treatment group, including age, race/ethnicity, gender, number of
previous overdoses, number of previous treatments for opiate use disorder, type of
opioid used, and depression. The model will yield predicted probabilities of BAC/CRC
group for all participants (the propensity score), and a five-level ordinal variable
based on the quintiles of the propensity score will be created. This ordinal variable
will be included as a stratum variable in our models.
Analyses for the primary aim: i.e. to evaluate the impact of the mobile, transitional
MAT intervention on its ability to engage participants in targeted, existing MAT
treatment slots at 1- and 6-month post-enrollment. For each of the 1- and 6-month time
points, the participants will be classified as being engaged/not-engaged (where
non-engaged will include dropped out or missing). The groups will be compared on
engagement rates at the two time points using a repeated measures logistic regression
model, incorporating the propensity score as described above (Diggle, Heagerty et al.
2002). The fixed effects will be binary indicators of treatment group and time point;
test for a group by time interaction to assess whether the group effect differs at month
1 and month 6. As there are only two time points, the use an unstructured covariance
matrix to accommodate within-participant covariance.
Analyses for Aim 2: Repeated measures model will be run to compare the groups on the ASI
(addiction severity index) drug composite score at month-1 and 6. The model will be
similar to that described for the engagement analyses of Aim 1, but with a beta
distribution assumed for the response, to accommodate the bounded range (zero to one) of
the ASI composite scores. The groups will be compared on the number of overdoses per
participants using repeated measures Poisson regression models, if there is sufficient
variability in the number of overdoses reported. If a low rate of overdoses causes
convergence issues for the Poisson model, participants will be classified as having no
overdose versus at least one, and compare the groups using repeated measures logistic
regression models.
Missing data. For the longitudinal analyses described above, premature discontinuation
from treatment and occasional missing daily use indicators will lead to incomplete data.
The repeated measures models described above can make use of all available data provided
by subjects, but the inferences drawn from them will be unaffected by the missing data
only if the missing data can be regarded as ignorable, essentially meaning that
missingness can be predicted/explained from the baseline data and from responses
obtained prior to drop-out. The sensitivity of our main analyses to the presence of
missing data will be assessed by performing a sensitivity analysis, in which estimates
of the group effect will be obtained under various non-ignorability assumptions.
Selection models will be used to examine the effects of missing data (Robins, Rotnitzky
et al. 1995), in which the probability of premature discontinuation at a time point as a
function of baseline characteristics and responses at previous time points will be
modeled using logistic regression models, and incorporate the predicted probabilities
into a weighted analysis of the main hypotheses.
Analyses for Aim 3: The total costs and per-participant costs of rapid initiation of MAT
for opioid treatment engagement will be estimated using a cost-offsets approach to
determine the economic value of this novel strategy. A cost-offsets approach requires a
comparison of the total cost of the intervention (proposed enhanced procedure or
treatment as usual) to the future costs of healthcare utilization avoided (i.e.,
benefits) due to the intervention. Healthcare utilization and medical costs will be
estimated before and after participants receive either rapid initiation of MAT for
opioid treatment engagement or treatment as usual. Information on healthcare utilization
will be collected from participants at each assessment when study-staff administer the
Non-Medical and Other Services Form (NSMOS; detailed description in Instruments
section). Medical costs associated with these treatments/services will be estimated
using Medicaid data.
4. Safety and Adverse Events 4.1. Data Safety Monitoring Plan (DSMP) For this study, the
University of Pennsylvania established procedures and infrastructure for data and safety
monitoring will be used. During the course of the study, safety and data quality
monitoring will be performed on an ongoing basis by the Principal Investigators and the
study staff. Study staff members are responsible for collecting and recording all
clinical data using the established MOP. This includes ensuring that all source
documents exist for the data on the Case Report Forms, ensuring all fields are completed
appropriately, and ensuring that all corrections are done according to Good Clinical
Practice (GCP). Any inconsistencies/deviations will be documented. The study Key
Personnel will review data on an ongoing basis and will document reviews by initialing
and dating reports. Study staff members conduct 100% quality assurance on data.
Staff training will consist of an explanation of the protocol and review of the e-Case Report
Forms. In addition, the duties of each staff person will be outlined and all applicable
regulations will be reviewed. Senior personnel will supervise junior staff and provide
re-training in the study protocol as needed.
The Independent Monitor for this study is the University of Pennsylvania Center for Studies
on Addiction DSMB. The DSMB will review the study every 6 months for all the duration of the
study. The DSMB form could be find in Appendix at the end of this document. The PI will
provide a summary of the status of the project that occurs during the reporting period. These
data will also be reported to CDC on an annual basis as part of the progress report. The DSMB
report will include the participants' socio-demographic characteristics, expected versus
actual recruitment rates, treatment retention rates, any quality assurance or regulatory
issues that occurred during the past year, summary of SAEs, and any actions or changes with
respect to the protocol.
4.2. Adverse Events Adverse events that occur at any point in the trial will be identified,
managed, and documented in accordance with reporting requirements of the the City IRB (the
IRB of record) and the sponsor (the CDC). Adverse events are defined as negative biologic
events and/or social harms that occur during the course of the trial. When needed, referrals
to medical treatment or specialists will be made. All patients will have comprehensive
psychiatric and medical screening prior to randomization and at each counseling and
assessment where evaluations for AEs will be routine. A member of the research team will be
available at all times to answer questions and assess possible AEs. Participants will be
withdrawn from the study if they show severe deterioration or if determined clinically
necessary for other reasons.
4.3 Internal Monitoring and Auditing
Oversight and Monitoring: The City of Philadelphia IRB will monitor the protection of human
subjects and the safe and secure collection and storage of data. This committee assesses all
studies before study initiation and then reviews protocols annually. The committee ensures
the scientific, technical, and statistical soundness of the research and guarantees that
methods for the ethical and safe treatment of human subjects are in place. The committee
scrutinizes the scientific and ethical aspects of protocols and provides for an objective and
ongoing assessment of the study's scientific and ethical integrity.
Protocol monitoring will ensure that the research protocol specified is being followed
without unauthorized deviations. Weekly meetings will be held to monitor the progress of the
trial. These meetings will involve the Principal Investigators, Co-Investigators, Project
Director, Site coordinator and other study staff. This will help to ensure standardized
application of the protocol and will serve as an ongoing mechanism by which project staff and
investigators will communicate in order to maintain a consistently high quality of study
conduct. Concerns identified will be addressed through training and retraining of personnel.
Database Auditing: Project director and RAs will review data entered into the database versus
that recorded on the CRFs. All accrued cases will be subjected to database auditing
throughout the duration of the trial. Depending on the data management findings, re-training
will be provided, should problems such as increased errors be detected.
Data Auditing: Project director and staff RAs will review safety data recorded on the CRF
versus that contained on the actual source document (client chart, EHR). All accrued cases
will be subjected to auditing throughout the duration of the trial. A Regulatory Binder
Review by OHR will include the following essential documents: IRB Protocol, Consent Form and
Amendment Approvals, IRB Closure Letter, List of Authorized Signatures, Laboratory
Certifications, Protocol and Amendment Signature Pages, Financial Disclosure Questionnaires,
and Monitoring Log. Additional monitoring by OHR may include: source documentation
verification; adverse event documentation; and facility assessment.
Data Security: Using network firewall technologies, the database will prevent the three major
sources of data security problems: unauthorized internal access to data, external access to
data, and malicious intent to destroy data and systems. Controlled user access will ensure
that only appropriate and authorized personnel are able to view, access, and modify trial
data. All modifications to data will document user access and data associated with the
modification, as well as values prior to modification.
Evidence of Training in Human Subject Research: All personnel working on this project will be
required to review the protocol, complete training in the protection of human subjects and
undergo training.
Confidentiality Since self-report and medical data will be collected and stored as part of
this study, it is possible that subject privacy or confidentiality can be threatened. To
address this concern, the Data Management System has set up several safeguards to prevent
unauthorized access to study data. An automatically generated index number is assigned to a
subject's study identification number (unique for personnel and clients). A linked subject
identification table is created for the storing of subject name, address and telephone
contact information. This table uses the automatically generated index number rather than the
study identification number. The master subject map and subject identification information
tables are maintained in a separate database. Using this method, no identifying subject
information is directly linked to medical information or other study data. The present
research team has not experienced the unauthorized use of study data. A web-based data
collection procedure will minimize the possibility of loss of privacy or confidentiality. The
risk of a potential breach of confidentiality is addressed in the informed consent documents.
Computers and Databases Trained staff will review all forms prior to the completion of the
study visit in an effort to minimize problems associated with missing values and incorrect
skip patterns. All assessments will be recorded on final version of the electronic Case
Reporting Forms (eCRFs). eCRFs will also be developed to capture the results of all
biological assessments. All eCRFs will be completed using only participant identifying
numbers and will not include names, addresses, or other data that could possibly be used to
disclose the identity of the participant. Research staff will be responsible for entering all
data into the secure web-based developed on REDCap (Research Electronic Data Capture). REDCap
is designed to comply with HIPAA regulations. Data will be input with secure web
authentication, data logging, and Secure Sockets Layer (SSL) encryption. REDCap allows
multisite access. It allows real-time data entry validation (e.g. for data types and range
checks), audit trails, and the ability to set up a calendar to schedule and track critical
study events such as participant visits.
