ADOPT: Alcohol Disorder hOsPital Treatment Trial

• Sponsor: Boston University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02478489
• Collaborator: National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH)
• Enrollment: 248
• Location: 1
• Arms: 2
• Actual Duration (Months): 52
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

The specific aims of this pragmatic randomized controlled trial are to compare initiating injectable extended release naltrexone (XR-NTX) or oral naltrexone (PO-NTX) at the time of discharge from a medical hospitalization for patients with alcohol use disorder (AUD) on: 1) alcohol consumption and consequences, and 2) acute healthcare utilization (including hospital readmission and emergency visits) and cost-effectiveness. In exploratory analyses, the investigators will assess moderators of medication effects including demographic, behavioral, and genetic factors.

Condition or Disease	Intervention/Treatment	Phase
Heavy Drinking; Alcohol Dependence; Alcohol Use Disorder	Drug: Oral naltrexone (PO-NTX); Drug: Extended-release injectable naltrexone (XR-NTX)	Phase 4

Detailed Description

Hospitalization for medical illness is a unique and missed opportunity for intervention for alcohol use disorders (AUDs). Referrals can help link patients from hospitals to alcohol treatment. But most patients return to heavy drinking after hospital discharge and do not follow-up with alcohol treatment, risking hospital readmission. Pharmacotherapy has efficacy for AUD, but adherence to these medications is poor. Furthermore, these medications are rarely prescribed in general medical settings, during or after hospitalization. Beginning treatment for AUD during a hospitalization for medical illness could broaden the reach of effective treatment and is likely to be more effective than delaying treatment until a specialist visit or treatment program entry. Hospital discharge is a time of both risk (i.e., for drinking and non-adherence to medical care) and opportunity (i.e., to begin alcohol treatment and complete medical treatments). Interventions that work quickly and improve adherence could improve medical and alcohol-related outcomes.

Oral naltrexone (PO-NTX), and the more-costly-per-dose long-acting injectable extended release naltrexone (XR-NTX) are Food and Drug Administration (FDA)-approved efficacious treatments for AUD. The XR-NTX half-life is 5-10 days and is dosed monthly, whereas the PO-NTX half-life is 13 hours and is dosed daily. The longer half-life of XR-NTX translates into patients receiving effective pharmacotherapy for a longer time without having to adhere to a daily dose. Thus, although more costly per dose, greater effectiveness could mean overall reduced costs of care (including alcohol-related health consequences and healthcare utilization). Despite potential differences in costs and patient preferences, PO-NTX and XR-NTX have not been directly compared in a randomized controlled trial (RCT), they have not been studied as treatments at medical hospital discharge, and their effectiveness in real world practice settings compared with standard care is unknown.

This trial is significant because it will address the clinically relevant comparative effectiveness question and lead to greater adoption of the most effective and cost-effective approach for treating AUD with pharmacotherapy in general hospitals.

Study Design

• Study Type: Interventional
• Actual Enrollment: 248 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oral v. Injection Naltrexone in Hospital: Comparative Effectiveness for Alcoholism
• Actual Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: Jul 1, 2020
• Actual Study Completion Date: Oct 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Extended-release injectable naltrexone (XR-NTX) Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks.	Drug: Extended-release injectable naltrexone (XR-NTX); injectable naltrexone; Other Names: Vivitrol
Active Comparator: Oral naltrexone (PO-NTX) Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking.	Drug: Oral naltrexone (PO-NTX); oral naltrexone; Other Names: Revia

Outcome Measures

Primary Outcome Measures

1. Change in Percent Heavy Drinking Days (%HDDs) Over the Past 30 Days From Baseline to 3 Month Follow-up, Assessed Using the Timeline Follow-Back [Baseline, 3 months]

   The primary alcohol use outcome will be change in percent heavy drinking days (%HDDs) from baseline to 3 month follow-up. %HDDs out of the past 30 days is assessed using the Timeline Follow-Back. %HDDs is the most likely (and most sensitive) to be affected by NTX and is clinically important (any reduction means less risk of harm). We chose self-report because biological testing is not sufficiently valid for detecting drinking levels and changes of clinical importance. The self-report tool is valid, particularly so when staff are well trained, and when the context for the subject is: they are informed they are being tested for consumption (breath alcohol and carbohydrate deficient transferrin (CDT), there are no consequences related to consumption levels, and that results are being recorded confidentially.

Secondary Outcome Measures

1. Acute Care Hospital Utilization [3 months]

   Any acute hospital utilization (emergency department visit or inpatient stay) over the past 90 days assessed at 3-month follow-up by the Form 90. Self-report for short-term high impact, memorable health utilization such as emergency and hospital stays is valid and can measure utilization at any site. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.

Other Outcome Measures

1. Medication Adherence [1, 2 and 3 months]

   High adherence to XR-NTX will be defined as administration of XR-NTX by the study nurse 3 times. Medium adherence will be defined as 1 or 2 injections. For PO-NTX, high adherence will be defined as participant self-report of taking PO-NTX for 90 out of the past 90 days at the 3 month study visit, and medium adherence as participant self-report of taking PO-NTX for 30-89 out of the past 90 days at the 3 month study visit (Form 90). We will also assess the presence of detectable beta-naltrexol to confirm reports of recent pill taking.

2. Alcohol Consequences Via Questionnaire [3 months]

   Alcohol consequences over the past 3 months will be measured by collecting participant self-report data via the Short Inventory of Problems (SIP-2R) at 3-month follow-up. The SIP-2R is a validated 15-item measure for assessing recent adverse consequences associated with alcohol use.

3. Alcohol Use Disorder-related Treatment Utilization Via Questionnaire and Health Records [3 months]

   Alcohol use disorder-related treatment utilization over the past 90 days assessed at 3-month follow-up by the Form 90. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.

4. Cost Via Utilization Questionnaire, Health Records and Estimates From Local and National Sources [3 and 12 months]

   Healthcare utilization cost data will be collected via the Form 90 for self-reported outpatient and emergency visits, hospitalizations, and specialty addiction treatment. Utilization episodes will be converted to costs by use of Medicare relative value units (RVUs) for acute inpatient care, Resource Based Relative Value System (RBRVS) units for Medicare reimbursement of outpatient visits, and the average daily rate for long-term care.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders (DSM) 5 alcohol use disorder (AUD) (assessed using Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS))

• ≥1 heavy drinking episodes (≥5 standard drinks [4 for women] in a day) in 30 days prior to hospitalization*

• Inpatient on a hospital general medical service

• Adult (age 18 years or greater)

• Ability to speak English (fluency)

• ≥2 contact persons*

Exclusion Criteria:

• Pregnancy (urine testing if childbearing potential)

• Currently breast-feeding

• Urine expanded panel drug test (dipstick) positive for opiates, semi-synthetic or synthetic opioids

• Opioid use (self-report and verification in medical record) in past 7 days for long-acting opioids

• Opioid use in past 24 hours for short-acting opioids

• Discharge prescription for opioids

• Future need for opioids for an anticipated painful event or surgery

• Known hypersensitivity to NTX

• Acute severe psychiatric illness (currently suicidal or psychotic)

• Cognitive dysfunction that precludes informed consent or research assistant (RA) assessment that subject cannot understand interview questions

• Alanine aminotransferase or aspartate aminotransferase >5 times the upper limit of normal

• Acute hepatitis

• Liver failure

• Known severe thrombocytopenia (<50,000)

• Coagulopathy

• Coagulation disorder

• Body habitus that precludes intramuscular injection

• Plans to leave the Boston area in less than one year

• Enrollment in a research study which involves taking a pharmaceutical agent that is expected to interact with naltrexone

[*criteria not changed since study start; change reflects correction of typo]

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Boston Medical Center	Boston	Massachusetts	United States	02118

Sponsors and Collaborators

• Boston University
• National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

• Principal Investigator: Richard Saitz, MD, MPH, Boston University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 24, 2020

More Information

Publications

None provided.

• Responsible Party: Boston University
• ClinicalTrials.gov Identifier: NCT02478489
• Other Study ID Numbers: H-32911; R01AA021335
• First Posted: Jun 23, 2015
• Last Update Posted: Jun 29, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by Boston University: alcohol; heavy drinking; naltrexone; hospital; alcohol use disorder; alcohol dependence; comparative effectiveness
• Additional relevant MeSH terms: Alcoholism; Alcohol Drinking; Naltrexone

Study Results

Participant Flow

Arm/Group Title	Extended-release Injectable Naltrexone (XR-NTX)	Oral Naltrexone (PO-NTX)
Arm/Group Description	Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks. Extended-release injectable naltrexone (XR-NTX): injectable naltrexone	Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking. Oral naltrexone (PO-NTX): oral naltrexone
Period Title: Overall Study
STARTED	123	125
COMPLETED	108	109
NOT COMPLETED	15	16

Baseline Characteristics

Arm/Group Title	Extended-release Injectable Naltrexone (XR-NTX)	Oral Naltrexone (PO-NTX)	Total
Arm/Group Description	Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks. Extended-release injectable naltrexone (XR-NTX): injectable naltrexone	Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking. Oral naltrexone (PO-NTX): oral naltrexone	Total of all reporting groups
Overall Participants	123	125	248
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.4 (10.3)	49.4 (10.5)	49.4 (10.4)
Sex: Female, Male (Count of Participants)
Female	24 19.5%	25 20%	49 19.8%
Male	99 80.5%	100 80%	199 80.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 16.3%	19 15.2%	39 15.7%
Not Hispanic or Latino	103 83.7%	106 84.8%	209 84.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	10 8.1%	3 2.4%	13 5.2%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	3 2.4%	2 1.6%	5 2%
Black or African American	61 49.6%	64 51.2%	125 50.4%
White	47 38.2%	54 43.2%	101 40.7%
More than one race	2 1.6%	2 1.6%	4 1.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Percent heavy drinking days over the past 30 days assessed at baseline by Timeline Followback (Percent heavy drinking days of past 30) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percent heavy drinking days of past 30]	70.7 (31.5)	66.7 (31.5)	68.7 (31.5)

Outcome Measures

1. Primary Outcome

Title	Change in Percent Heavy Drinking Days (%HDDs) Over the Past 30 Days From Baseline to 3 Month Follow-up, Assessed Using the Timeline Follow-Back
Description	The primary alcohol use outcome will be change in percent heavy drinking days (%HDDs) from baseline to 3 month follow-up. %HDDs out of the past 30 days is assessed using the Timeline Follow-Back. %HDDs is the most likely (and most sensitive) to be affected by NTX and is clinically important (any reduction means less risk of harm). We chose self-report because biological testing is not sufficiently valid for detecting drinking levels and changes of clinical importance. The self-report tool is valid, particularly so when staff are well trained, and when the context for the subject is: they are informed they are being tested for consumption (breath alcohol and carbohydrate deficient transferrin (CDT), there are no consequences related to consumption levels, and that results are being recorded confidentially.
Time Frame	Baseline, 3 months

Outcome Measure Data

Analysis Population Description

Analysis population includes those who completed the 3 month follow-up assessment. Population does not match baseline sample due to attrition / loss to follow-up.

Arm/Group Title	Extended-release Injectable Naltrexone (XR-NTX)	Oral Naltrexone (PO-NTX)
Arm/Group Description	Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks. Extended-release injectable naltrexone (XR-NTX): injectable naltrexone	Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking. Oral naltrexone (PO-NTX): oral naltrexone
Measure Participants	108	109
Mean (Standard Deviation) [change in percent heavy drinking days]	-46.4 (38.5)	-38.4 (43.3)

2. Secondary Outcome

Title	Acute Care Hospital Utilization
Description	Any acute hospital utilization (emergency department visit or inpatient stay) over the past 90 days assessed at 3-month follow-up by the Form 90. Self-report for short-term high impact, memorable health utilization such as emergency and hospital stays is valid and can measure utilization at any site. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Analysis population includes those who completed the 3 month follow-up assessment. Population does not match baseline sample due to attrition / loss to follow-up.

Arm/Group Title	Extended-release Injectable Naltrexone (XR-NTX)	Oral Naltrexone (PO-NTX)
Arm/Group Description	Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks. Extended-release injectable naltrexone (XR-NTX): injectable naltrexone	Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking. Oral naltrexone (PO-NTX): oral naltrexone
Measure Participants	108	109
Any acute care hospital utilization (emergency department visit or inpatient stay)	66 53.7%	59 47.2%
No acute care hospital utilization (emergency department visit or inpatient stay)	42 34.1%	50 40%

3. Other Pre-specified Outcome

Title	Medication Adherence
Description	High adherence to XR-NTX will be defined as administration of XR-NTX by the study nurse 3 times. Medium adherence will be defined as 1 or 2 injections. For PO-NTX, high adherence will be defined as participant self-report of taking PO-NTX for 90 out of the past 90 days at the 3 month study visit, and medium adherence as participant self-report of taking PO-NTX for 30-89 out of the past 90 days at the 3 month study visit (Form 90). We will also assess the presence of detectable beta-naltrexol to confirm reports of recent pill taking.
Time Frame	1, 2 and 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Other Pre-specified Outcome

Title	Alcohol Consequences Via Questionnaire
Description	Alcohol consequences over the past 3 months will be measured by collecting participant self-report data via the Short Inventory of Problems (SIP-2R) at 3-month follow-up. The SIP-2R is a validated 15-item measure for assessing recent adverse consequences associated with alcohol use.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Alcohol Use Disorder-related Treatment Utilization Via Questionnaire and Health Records
Description	Alcohol use disorder-related treatment utilization over the past 90 days assessed at 3-month follow-up by the Form 90. Using the clinical data warehouse at one site (Boston Medical Center (BMC)) and statewide data, we will compare self-report to the utilization databases. But, self-report data will remain primary, with databases used to provide a descriptive frame of reference.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Cost Via Utilization Questionnaire, Health Records and Estimates From Local and National Sources
Description	Healthcare utilization cost data will be collected via the Form 90 for self-reported outpatient and emergency visits, hospitalizations, and specialty addiction treatment. Utilization episodes will be converted to costs by use of Medicare relative value units (RVUs) for acute inpatient care, Resource Based Relative Value System (RBRVS) units for Medicare reimbursement of outpatient visits, and the average daily rate for long-term care.
Time Frame	3 and 12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Events were collected until the participant's 3-month follow-up research assessment was completed or their follow-up window closed.
Arm/Group Title	Extended-release Injectable Naltrexone (XR-NTX)		Oral Naltrexone (PO-NTX)
Arm/Group Description	Monthly XR-NTX (380 mg) Subjects randomized to XR-NTX will receive one intramuscular gluteal injection (in accordance with the FDA approved label/package insert) of 380 mg of NTX for extended-release injectable suspension at study entry (in the hospital) and 1, and 2 months later (outpatient in the primary care clinic), alternating buttocks. Extended-release injectable naltrexone (XR-NTX): injectable naltrexone		Daily PO-NTX (50 mg, up to 100 mg if heavy drinking continues) Subjects randomized to PO-NTX will receive a study prescription (first one in the hospital)(fillable only at the medical center research pharmacy and prepared by the research pharmacist) for a 1-month supply of oral NTX to be taken once daily- 25 mg a day for 3 days, then 50 mg a day. If the subject has a prior history of taking PO-NTX and tolerating it well, the participant may be started at 50 mg. The dose may be increased to 100 mg daily for any participant who continues to have heavy drinking. Oral naltrexone (PO-NTX): oral naltrexone
All Cause Mortality
	Extended-release Injectable Naltrexone (XR-NTX)		Oral Naltrexone (PO-NTX)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/123 (1.6%)		3/125 (2.4%)
Serious Adverse Events
	Extended-release Injectable Naltrexone (XR-NTX)		Oral Naltrexone (PO-NTX)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/123 (35%)		43/125 (34.4%)
Cardiac disorders
Chest Pain	1/123 (0.8%)		4/125 (3.2%)
Congestive Heart Failure	2/123 (1.6%)		1/125 (0.8%)
Heart Failure	1/123 (0.8%)		0/125 (0%)
Hypertension	1/123 (0.8%)		0/125 (0%)
Hypotension	1/123 (0.8%)		0/125 (0%)
Palpitations	0/123 (0%)		1/125 (0.8%)
Syncope	3/123 (2.4%)		1/125 (0.8%)
Endocrine disorders
Diabetic Ketoacidosis	1/123 (0.8%)		2/125 (1.6%)
Hyperglycemia	0/123 (0%)		2/125 (1.6%)
Hypoglycemia	0/123 (0%)		1/125 (0.8%)
Gastrointestinal disorders
Abdominal Pain	1/123 (0.8%)		4/125 (3.2%)
Epigastric Pain	0/123 (0%)		2/125 (1.6%)
Pancreatitis	0/123 (0%)		2/125 (1.6%)
Rectal Bleeding	0/123 (0%)		1/125 (0.8%)
Vomiting	2/123 (1.6%)		3/125 (2.4%)
General disorders
Death	2/123 (1.6%)		3/125 (2.4%)
Fatigue	1/123 (0.8%)		0/125 (0%)
Weakness	1/123 (0.8%)		0/125 (0%)
Hepatobiliary disorders
Acute Cholecystitis	0/123 (0%)		1/125 (0.8%)
Infections and infestations
Coronavirus (COVID-19)	0/123 (0%)		1/125 (0.8%)
Osteomylelitis of Toe	0/123 (0%)		1/125 (0.8%)
Injury, poisoning and procedural complications
Fall	2/123 (1.6%)		1/125 (0.8%)
Intoxication	3/123 (2.4%)		0/125 (0%)
Traumatic Injury	1/123 (0.8%)		0/125 (0%)
Metabolism and nutrition disorders
Hypokalemia	0/123 (0%)		1/125 (0.8%)
Musculoskeletal and connective tissue disorders
Ankle Fracture	0/123 (0%)		2/125 (1.6%)
Ankle Pain	1/123 (0.8%)		0/125 (0%)
Back Pain	1/123 (0.8%)		0/125 (0%)
Foot Pain	0/123 (0%)		1/125 (0.8%)
Left Hand Tenosynovitis	1/123 (0.8%)		0/125 (0%)
Lower Extremity Pain	0/123 (0%)		1/125 (0.8%)
Nervous system disorders
Altered Mental Status	1/123 (0.8%)		0/125 (0%)
Basal Ganglia Hemorrage	1/123 (0.8%)		0/125 (0%)
Dizziness	1/123 (0.8%)		0/125 (0%)
Loss of consciousness	0/123 (0%)		1/125 (0.8%)
Seizure	5/123 (4.1%)		2/125 (1.6%)
Subdural Hematoma	0/123 (0%)		1/125 (0.8%)
Thoracic Osteomyelitis	0/123 (0%)		1/125 (0.8%)
Psychiatric disorders
Alcohol Withdrawal	6/123 (4.9%)		10/125 (8%)
Anxiety	0/123 (0%)		1/125 (0.8%)
Depression	0/123 (0%)		1/125 (0.8%)
Hallucinations	0/123 (0%)		1/125 (0.8%)
Psychiatric Hospitalization	1/123 (0.8%)		0/125 (0%)
Seeking Detox	1/123 (0.8%)		0/125 (0%)
Suicidal Ideation	1/123 (0.8%)		2/125 (1.6%)
Suicide Attempt	1/123 (0.8%)		1/125 (0.8%)
Renal and urinary disorders
Urinary Tract Infection	0/123 (0%)		1/125 (0.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/123 (0.8%)		1/125 (0.8%)
Bronchitis	0/123 (0%)		1/125 (0.8%)
Chronic Obstructive Pulmonary Disease	4/123 (3.3%)		1/125 (0.8%)
Interstitial Lung Disease	1/123 (0.8%)		0/125 (0%)
Pneumonia	4/123 (3.3%)		2/125 (1.6%)
Respiratory Failure	0/123 (0%)		1/125 (0.8%)
Shortness of Breath	3/123 (2.4%)		0/125 (0%)
Skin and subcutaneous tissue disorders
Cellulitis	0/123 (0%)		1/125 (0.8%)
Injection Site Abscess	1/123 (0.8%)		0/0 (NaN)
Surgical and medical procedures
Laparoscopic Cholecystectomy	0/123 (0%)		1/125 (0.8%)
Vascular disorders
Pulmonary embolism	1/123 (0.8%)		0/125 (0%)
Other (Not Including Serious) Adverse Events
	Extended-release Injectable Naltrexone (XR-NTX)		Oral Naltrexone (PO-NTX)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/123 (48%)		39/125 (31.2%)
Hepatobiliary disorders
Elevated Liver Function Tests	19/123 (15.4%)		32/125 (25.6%)
Injury, poisoning and procedural complications
Intoxication	16/123 (13%)		12/125 (9.6%)
Skin and subcutaneous tissue disorders
Injection Site Discomfort	36/123 (29.3%)		0/0 (NaN)

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.