Oral vs. Injectable Naltrexone for Hospitalized Veterans With Alcohol Dependence
Study Details
Study Description
Brief Summary
The over-arching goal of the proposed project is to understand the impact of medication adherence upon engagement in behavioral treatment for alcohol use disorders. The proposed project is a pilot feasibility study of inpatient veterans with problem alcohol use at the William S. Middleton VA Hospital (Madison, WI). Participants will be randomized to one of two parallel study conditions: (1) an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone, or (2) a single 380 mg intramuscular injection of naltrexone administered prior to discharge and a second injection one month later. The central hypothesis is that hospital-administered injectable naltrexone, when compared to daily oral naltrexone taken at home, will reduce alcohol use in the days immediately following hospitalization. Injectable naltrexone has been efficacious vs. placebo in addition to behavioral treatment in several studies. However, it has yet to be examined in head-to-head comparison with oral naltrexone, or in the hospital setting as an intervention that might facilitate behavioral treatment follow up after discharge.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
The proposed project is a pilot feasibility study of inpatient veterans with problem alcohol use at the William S. Middleton VA Hospital. The over-arching goal is to understand the impact of medication adherence upon engagement in behavioral treatment for alcohol use disorders. Participants will be randomized to one of two parallel study conditions: (1) an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone, or (2) a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days) administered prior to discharge followed by a second injection one month later. The central hypothesis is that hospital-administered, long-acting injectable naltrexone, when compared to daily oral naltrexone, will reduce alcohol use in the days immediately following hospitalization. This reduced consumption, we hypothesize, will be followed by improved engagement in substance abuse treatment.
Primary Aim: Demonstrate the feasibility of the proposed recruitment methods and study design. This aim comprises two measures with corresponding goals: (1) Recruitment/enrollment-with a recruitment goal of 50 eligible and consenting subjects in an 8 month time period, and (2) Follow-up data collection with a goal of post-hospitalization follow-up data on no less than 70% of enrolled subjects.
Secondary Aims: As a pilot feasibility study, we may not anticipate sufficient power to attain statistical significance on patient-oriented outcome measures. However, it will be important for us to consider and to evaluate pertinent outcomes and potential moderators in order to (1) develop and fine-tune study design, and (2) determine effect sizes for primary outcomes so that we may calculate appropriate sample sizes for future larger study. As such, the secondary aims for the current study are:
-
To compare injectable naltrexone study to oral naltrexone in terms of attendance to recommended outpatient substance abuse treatment. We hypothesize that injectable naltrexone will be associated with improved likelihood of attending initial visits for substance abuse treatment.
-
To compare study arms in terms of ongoing alcohol consumption. We hypothesize that (1) improved medication adherence in the oral naltrexone arm and (2) assignment to injectable naltrexone will be associated with reduced alcohol consumption (number of heavy drinking days in the past 14 days) following hospital discharge.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: oral naltrexone an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone |
Drug: Naltrexone
Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence.
Other Names:
|
| Experimental: injectable naltrexone a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. |
Drug: Naltrexone
Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Retention Rate: Percentage of Participants Attended an Initial Behavioral Treatment Visit Within 2 Weeks of Hospital Discharge. [12 months]
Retention rate was measured in terms of percentage of participants attended an initial behavioral treatment visit within 2 weeks of hospital discharge.
Secondary Outcome Measures
- Percentage of Patients Attended Recommended Outpatient Substance Abuse Treatment [12 months]
Attendance to recommended outpatient substance abuse treatment will be compared between injectable naltrexone group and oral naltrexone group. Keeping patients engaged in treatment is desirable and is known to improve addiction-related outcomes.
- Percentage of Participants Adhered to Medication [12 months]
Medication adherence was measured as percentage of participants who took ≥ 80% of daily naltrexone doses determined via pill counts. Adherence of daily medication will predict treatment engagement following hospital discharge.
- Ongoing Alcohol Consumption [12 months]
To compare study arms in terms of ongoing alcohol consumption. We hypothesize that (1) improved medication adherence in the oral naltrexone arm and (2) assignment to injectable naltrexone will be associated with reduced alcohol consumption (number of heavy drinking days in the past 14 days) following hospital discharge.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 years or older
-
diagnostic criteria for alcohol dependence or abuse
-
women of childbearing potential who have a negative screening urine pregnancy test and are willing to use reliable birth control methods throughout the duration of the study
Exclusion Criteria:
-
active or recently active (less than 1 year) opioid dependence or daily use of opioid analgesics
-
acute hepatitis or liver failure
-
pregnancy
-
women who are currently breastfeeding
-
active suicidality
-
inability to provide written informed consent as determined by study comprehension questions
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Wisconsin - Department of Family Medicine | Madison | Wisconsin | United States | 53715 |
Sponsors and Collaborators
- University of Wisconsin, Madison
Investigators
- Principal Investigator: Randall T Brown, MD PhD, University of Wisconsin, Madison
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2012-0702
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 9 participants who didn't receive medication were discharged from the hospital before they could get medication. Therefore, only 45 , out of 54 participants got the medication. |
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone |
|---|---|---|
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. |
| Period Title: Overall Study | ||
| STARTED | 23 | 22 |
| Lost to 14 Day Follow up | 6 | 2 |
| Lost to 45 Day Follow up | 1 | 1 |
| COMPLETED | 16 | 19 |
| NOT COMPLETED | 7 | 3 |
Baseline Characteristics
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone | Total |
|---|---|---|---|
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. | Total of all reporting groups |
| Overall Participants | 23 | 22 | 45 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
15
65.2%
|
16
72.7%
|
31
68.9%
|
| >=65 years |
8
34.8%
|
6
27.3%
|
14
31.1%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
50.9
(14.5)
|
48.3
(12.9)
|
49.5
(13.9)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
1
4.3%
|
21
95.5%
|
22
48.9%
|
| Male |
22
95.7%
|
1
4.5%
|
23
51.1%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
3
13%
|
2
9.1%
|
5
11.1%
|
| White |
20
87%
|
20
90.9%
|
40
88.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
23
100%
|
22
100%
|
45
100%
|
Outcome Measures
| Title | Retention Rate: Percentage of Participants Attended an Initial Behavioral Treatment Visit Within 2 Weeks of Hospital Discharge. |
|---|---|
| Description | Retention rate was measured in terms of percentage of participants attended an initial behavioral treatment visit within 2 weeks of hospital discharge. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone |
|---|---|---|
| Arm/Group Description | enrolled and received oral naltrexone | enrolled and received injectable naltrexone |
| Measure Participants | 23 | 22 |
| Count of Participants [Participants] |
23
100%
|
22
100%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Oral Naltrexone, Injectable Naltrexone |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.71 | |
| Confidence Interval |
(2-Sided) 95% 0.35 to 9.98 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Patients Attended Recommended Outpatient Substance Abuse Treatment |
|---|---|
| Description | Attendance to recommended outpatient substance abuse treatment will be compared between injectable naltrexone group and oral naltrexone group. Keeping patients engaged in treatment is desirable and is known to improve addiction-related outcomes. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone |
|---|---|---|
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. |
| Measure Participants | 23 | 22 |
| Count of Participants [Participants] |
19
82.6%
|
18
81.8%
|
| Title | Percentage of Participants Adhered to Medication |
|---|---|
| Description | Medication adherence was measured as percentage of participants who took ≥ 80% of daily naltrexone doses determined via pill counts. Adherence of daily medication will predict treatment engagement following hospital discharge. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone |
|---|---|---|
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. 62% of injection group and 61% of oral group met study definition of adherence | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. 62% of injection group and 61% of oral group met study definition of adherence |
| Measure Participants | 23 | 22 |
| Count of Participants [Participants] |
14
60.9%
|
14
63.6%
|
| Title | Ongoing Alcohol Consumption |
|---|---|
| Description | To compare study arms in terms of ongoing alcohol consumption. We hypothesize that (1) improved medication adherence in the oral naltrexone arm and (2) assignment to injectable naltrexone will be associated with reduced alcohol consumption (number of heavy drinking days in the past 14 days) following hospital discharge. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone |
|---|---|---|
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. 62% of injection group and 61% of oral group met study definition of adherence | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. Among those who were randomized (n=54), 64.8% (n=35) received a study medication and completed all follow-ups. Among those received a study medication and were proactively followed (n=45), 77% completed all follow-ups. 62% of injection group and 61% of oral group met study definition of adherence |
| Measure Participants | 23 | 22 |
| Mean (Inter-Quartile Range) [Total drinks] |
136.5
|
114.5
|
Adverse Events
| Time Frame | from September 5, 2013 to April 20, 2015, for a total accrual time of 19 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Oral Naltrexone | Injectable Naltrexone | ||
| Arm/Group Description | an initial 50 mg oral dose of naltrexone prior to hospital discharge plus a 30-day prescription for oral naltrexone Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. | a single 380 mg intramuscular injection of naltrexone (duration of action = 30 days)prior to hospital discharge followed by a second injection one month later. Naltrexone: Naltexone was chosen for this study because naltrexone is the only medication available in both oral daily and injectable monthly formulations, which will allow the study to examine issues around medication adherence. | ||
All Cause Mortality |
||||
| Oral Naltrexone | Injectable Naltrexone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Oral Naltrexone | Injectable Naltrexone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/22 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Oral Naltrexone | Injectable Naltrexone | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/23 (4.3%) | 0/22 (0%) | ||
| Psychiatric disorders | ||||
| depression | 1/23 (4.3%) | 1 | 0/22 (0%) | 0 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Randall Brown |
|---|---|
| Organization | University of Wisconsin |
| Phone | 6082636558 |
| rtbrown@wisc.edu |
- 2012-0702