Trial Outcomes & Findings for Surmounting Withdrawal to Initiate Fast Treatment With Naltrexone (NCT NCT04762537)
NCT ID: NCT04762537
Last Updated: 2023-09-18
Results Overview
The primary goal of the study is to show RP is non-inferior to SP XR-NTX induction method.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
415 participants
Primary outcome timeframe
Induction Phase: 1-30 days
Results posted on
2023-09-18
Participant Flow
451 participants were found eligible at pre-screening, 32 of which did not meet eligibility criteria at screening. Of the 419 participants determined eligible at screening, 4 withdrew interest in participation or left prior to completion of screening and initiation of enrollment. The total remaining 415 were enrolled in one of the study treatment arms.
Unit of analysis: Sites
Participant milestones
| Measure |
Site 1: Rapid Procedure for Duration of Study (70 Weeks)
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Site 2: 14 Weeks of Standard Procedure, Followed by 56 Weeks of Rapid Procedure
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
\--
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Site 3: 28 Weeks of Standard Procedure, Followed by 42 Weeks of Rapid Procedure
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Site 4: 42 Weeks of Standard Procedure, Followed by 28 Weeks of Rapid Procedure
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Site 5: "Standard Procedure for 56 Weeks, Followed by 14 Weeks of Rapid Procedure
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Site 6: Standard Procedure for Duration of the Study (70 Weeks)
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
|---|---|---|---|---|---|---|
|
Step 1 (Weeks 0-14)
STARTED
|
14 1
|
14 1
|
6 1
|
25 1
|
15 1
|
8 1
|
|
Step 1 (Weeks 0-14)
COMPLETED
|
7 1
|
6 1
|
1 1
|
6 1
|
12 1
|
1 1
|
|
Step 1 (Weeks 0-14)
NOT COMPLETED
|
7 0
|
8 0
|
5 0
|
19 0
|
3 0
|
7 0
|
|
Step 2 (Weeks 14-28)
STARTED
|
7 1
|
25 1
|
9 1
|
24 1
|
13 1
|
6 1
|
|
Step 2 (Weeks 14-28)
COMPLETED
|
4 1
|
19 1
|
5 1
|
7 1
|
7 1
|
3 1
|
|
Step 2 (Weeks 14-28)
NOT COMPLETED
|
3 0
|
6 0
|
4 0
|
17 0
|
6 0
|
3 0
|
|
Step 3 (Weeks 28-42)
STARTED
|
10 1
|
23 1
|
12 1
|
15 1
|
13 1
|
7 1
|
|
Step 3 (Weeks 28-42)
COMPLETED
|
2 1
|
14 1
|
9 1
|
5 1
|
4 1
|
3 1
|
|
Step 3 (Weeks 28-42)
NOT COMPLETED
|
8 0
|
9 0
|
3 0
|
10 0
|
9 0
|
4 0
|
|
Step 4 (Weeks 42-56)
STARTED
|
15 1
|
32 1
|
4 1
|
23 1
|
18 1
|
12 1
|
|
Step 4 (Weeks 42-56)
COMPLETED
|
11 1
|
19 1
|
2 1
|
14 1
|
8 1
|
1 1
|
|
Step 4 (Weeks 42-56)
NOT COMPLETED
|
4 0
|
13 0
|
2 0
|
9 0
|
10 0
|
11 0
|
|
Step 5 (Weeks 56-70)
STARTED
|
6 1
|
13 1
|
5 1
|
12 1
|
24 1
|
5 1
|
|
Step 5 (Weeks 56-70)
COMPLETED
|
4 1
|
10 1
|
3 1
|
11 1
|
12 1
|
1 1
|
|
Step 5 (Weeks 56-70)
NOT COMPLETED
|
2 0
|
3 0
|
2 0
|
1 0
|
12 0
|
4 0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Not all participants who enrolled and participated in baseline data collection had COWS collected on first day of admission (baseline assessments were conducted most frequently after the first day of admission)
Baseline characteristics by cohort
| Measure |
Standard Induction Method
n=190 Participants
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
Rapid Induction Method
n=225 Participants
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
Total
n=415 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=190 Participants
|
2 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=190 Participants
|
24 Participants
n=225 Participants
|
46 Participants
n=415 Participants
|
|
Age, Categorical
>=65 years
|
168 Participants
n=190 Participants
|
199 Participants
n=225 Participants
|
367 Participants
n=415 Participants
|
|
Sex: Female, Male
Female
|
77 Participants
n=190 Participants
|
133 Participants
n=225 Participants
|
210 Participants
n=415 Participants
|
|
Sex: Female, Male
Male
|
113 Participants
n=190 Participants
|
92 Participants
n=225 Participants
|
205 Participants
n=415 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
38 Participants
n=190 Participants
|
53 Participants
n=225 Participants
|
91 Participants
n=415 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
147 Participants
n=190 Participants
|
172 Participants
n=225 Participants
|
319 Participants
n=415 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
5 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
4 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
5 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Participants
n=190 Participants
|
2 Participants
n=225 Participants
|
6 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
28 Participants
n=190 Participants
|
26 Participants
n=225 Participants
|
54 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Pacific Islander
|
1 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
White
|
115 Participants
n=190 Participants
|
175 Participants
n=225 Participants
|
290 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Other
|
12 Participants
n=190 Participants
|
11 Participants
n=225 Participants
|
23 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Multiracial
|
16 Participants
n=190 Participants
|
6 Participants
n=225 Participants
|
22 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Don't Know
|
10 Participants
n=190 Participants
|
2 Participants
n=225 Participants
|
12 Participants
n=415 Participants
|
|
Race/Ethnicity, Customized
Refused to Answer
|
0 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
1 Participants
n=415 Participants
|
|
Region of Enrollment
United States
|
190 Participants
n=190 Participants
|
225 Participants
n=225 Participants
|
415 Participants
n=415 Participants
|
|
Education Completed
Less than high school diploma
|
39 Participants
n=190 Participants
|
49 Participants
n=225 Participants
|
88 Participants
n=415 Participants
|
|
Education Completed
High school graduate
|
58 Participants
n=190 Participants
|
69 Participants
n=225 Participants
|
127 Participants
n=415 Participants
|
|
Education Completed
GED or equivalent
|
24 Participants
n=190 Participants
|
34 Participants
n=225 Participants
|
58 Participants
n=415 Participants
|
|
Education Completed
Some college, no degree
|
38 Participants
n=190 Participants
|
40 Participants
n=225 Participants
|
78 Participants
n=415 Participants
|
|
Education Completed
Associate's degree: occupational, technical, or vocational program
|
11 Participants
n=190 Participants
|
9 Participants
n=225 Participants
|
20 Participants
n=415 Participants
|
|
Education Completed
Associate's degree: academic program
|
11 Participants
n=190 Participants
|
8 Participants
n=225 Participants
|
19 Participants
n=415 Participants
|
|
Education Completed
Bachelor's degree
|
4 Participants
n=190 Participants
|
7 Participants
n=225 Participants
|
11 Participants
n=415 Participants
|
|
Education Completed
Master's degree
|
3 Participants
n=190 Participants
|
3 Participants
n=225 Participants
|
6 Participants
n=415 Participants
|
|
Education Completed
Professional school degree
|
0 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
0 Participants
n=415 Participants
|
|
Education Completed
Doctoral degree
|
0 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
0 Participants
n=415 Participants
|
|
Education Completed
Don't know
|
2 Participants
n=190 Participants
|
6 Participants
n=225 Participants
|
8 Participants
n=415 Participants
|
|
Marital Status
Married
|
15 Participants
n=190 Participants
|
16 Participants
n=225 Participants
|
31 Participants
n=415 Participants
|
|
Marital Status
Widowed
|
4 Participants
n=190 Participants
|
7 Participants
n=225 Participants
|
11 Participants
n=415 Participants
|
|
Marital Status
Divorced
|
23 Participants
n=190 Participants
|
28 Participants
n=225 Participants
|
51 Participants
n=415 Participants
|
|
Marital Status
Separated
|
15 Participants
n=190 Participants
|
15 Participants
n=225 Participants
|
30 Participants
n=415 Participants
|
|
Marital Status
Never married
|
112 Participants
n=190 Participants
|
121 Participants
n=225 Participants
|
233 Participants
n=415 Participants
|
|
Marital Status
Living with partner
|
16 Participants
n=190 Participants
|
28 Participants
n=225 Participants
|
44 Participants
n=415 Participants
|
|
Marital Status
Don't know
|
4 Participants
n=190 Participants
|
10 Participants
n=225 Participants
|
14 Participants
n=415 Participants
|
|
Marital Status
Refused
|
1 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
1 Participants
n=415 Participants
|
|
Sexual-Orientation
Missing
|
23 Participants
n=190 Participants
|
21 Participants
n=225 Participants
|
44 Participants
n=415 Participants
|
|
Sexual-Orientation
Heterosexual or straight
|
146 Participants
n=190 Participants
|
173 Participants
n=225 Participants
|
319 Participants
n=415 Participants
|
|
Sexual-Orientation
Gay or lesbian
|
2 Participants
n=190 Participants
|
4 Participants
n=225 Participants
|
6 Participants
n=415 Participants
|
|
Sexual-Orientation
Bisexual
|
15 Participants
n=190 Participants
|
24 Participants
n=225 Participants
|
39 Participants
n=415 Participants
|
|
Sexual-Orientation
Queer
|
2 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Sexual-Orientation
Not sure
|
1 Participants
n=190 Participants
|
2 Participants
n=225 Participants
|
3 Participants
n=415 Participants
|
|
Sexual-Orientation
Something else
|
1 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Employment
Working now
|
50 Participants
n=190 Participants
|
52 Participants
n=225 Participants
|
102 Participants
n=415 Participants
|
|
Employment
Only temporarily laid off, sick leave, or maternity leave
|
5 Participants
n=190 Participants
|
15 Participants
n=225 Participants
|
20 Participants
n=415 Participants
|
|
Employment
Looking for work, unemployed
|
121 Participants
n=190 Participants
|
140 Participants
n=225 Participants
|
261 Participants
n=415 Participants
|
|
Employment
Retired
|
1 Participants
n=190 Participants
|
0 Participants
n=225 Participants
|
1 Participants
n=415 Participants
|
|
Employment
Disabled permanently or temporarily
|
6 Participants
n=190 Participants
|
4 Participants
n=225 Participants
|
10 Participants
n=415 Participants
|
|
Employment
Keeping house
|
3 Participants
n=190 Participants
|
12 Participants
n=225 Participants
|
15 Participants
n=415 Participants
|
|
Employment
Student
|
1 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Employment
Other
|
3 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
4 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Missing
|
22 Participants
n=190 Participants
|
32 Participants
n=225 Participants
|
54 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Own apartment, room or house - subsidized, for example Section 8 or living in public housing
|
9 Participants
n=190 Participants
|
3 Participants
n=225 Participants
|
12 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Own apartment, room or house - not subsidized
|
47 Participants
n=190 Participants
|
84 Participants
n=225 Participants
|
131 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Someone else's apartment, room or house
|
66 Participants
n=190 Participants
|
65 Participants
n=225 Participants
|
131 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Hotel, SRO, or boarding home
|
17 Participants
n=190 Participants
|
8 Participants
n=225 Participants
|
25 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Halfway house, residential treatment program (focus: establishing sobriety)
|
1 Participants
n=190 Participants
|
3 Participants
n=225 Participants
|
4 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Transitional housing (focus: movement into permanent housing)
|
1 Participants
n=190 Participants
|
2 Participants
n=225 Participants
|
3 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Institution (hospital, nursing home, etc.)
|
4 Participants
n=190 Participants
|
3 Participants
n=225 Participants
|
7 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Homeless shelter
|
4 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
5 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Outdoors/street, abandoned/public building, vehicle, or other place not meant for human habitation
|
11 Participants
n=190 Participants
|
11 Participants
n=225 Participants
|
22 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Detox
|
1 Participants
n=190 Participants
|
1 Participants
n=225 Participants
|
2 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Other - homeless
|
3 Participants
n=190 Participants
|
3 Participants
n=225 Participants
|
6 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Other - stable housing
|
1 Participants
n=190 Participants
|
4 Participants
n=225 Participants
|
5 Participants
n=415 Participants
|
|
Location participant spent the night before coming to the unit
Other
|
3 Participants
n=190 Participants
|
5 Participants
n=225 Participants
|
8 Participants
n=415 Participants
|
|
First COWS Score on Day 1 of admission
|
5.7 units on a scale
STANDARD_DEVIATION 4.50 • n=146 Participants • Not all participants who enrolled and participated in baseline data collection had COWS collected on first day of admission (baseline assessments were conducted most frequently after the first day of admission)
|
4.8 units on a scale
STANDARD_DEVIATION 3.53 • n=201 Participants • Not all participants who enrolled and participated in baseline data collection had COWS collected on first day of admission (baseline assessments were conducted most frequently after the first day of admission)
|
5.2 units on a scale
STANDARD_DEVIATION 3.99 • n=347 Participants • Not all participants who enrolled and participated in baseline data collection had COWS collected on first day of admission (baseline assessments were conducted most frequently after the first day of admission)
|
|
History of lifetime opioid overdose
|
89 Participants
n=190 Participants
|
111 Participants
n=225 Participants
|
200 Participants
n=415 Participants
|
|
Number of lifetime overdoses
|
4.5 overdoses
STANDARD_DEVIATION 6.92 • n=88 Participants • 89 participants in Standard Procedure indicated history of overdose in their lifetime, and 88 of them provided data on the total number of overdoses via self-report (1 missing). 111 participants in Rapid Procedure indicated history of overdose in their lifetime, and all of them provided data on the total number of overdoses via self-reporting (none missing).
|
4.1 overdoses
STANDARD_DEVIATION 4.59 • n=111 Participants • 89 participants in Standard Procedure indicated history of overdose in their lifetime, and 88 of them provided data on the total number of overdoses via self-report (1 missing). 111 participants in Rapid Procedure indicated history of overdose in their lifetime, and all of them provided data on the total number of overdoses via self-reporting (none missing).
|
4.3 overdoses
STANDARD_DEVIATION 5.73 • n=199 Participants • 89 participants in Standard Procedure indicated history of overdose in their lifetime, and 88 of them provided data on the total number of overdoses via self-report (1 missing). 111 participants in Rapid Procedure indicated history of overdose in their lifetime, and all of them provided data on the total number of overdoses via self-reporting (none missing).
|
|
Baseline substance use (Urine Drug Screen)
Opiates
|
38 Number of positive test results
n=190 Participants
|
64 Number of positive test results
n=225 Participants
|
102 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Oxycodone
|
11 Number of positive test results
n=190 Participants
|
7 Number of positive test results
n=225 Participants
|
18 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Methadone
|
7 Number of positive test results
n=190 Participants
|
4 Number of positive test results
n=225 Participants
|
11 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Buprenorphine
|
127 Number of positive test results
n=190 Participants
|
129 Number of positive test results
n=225 Participants
|
256 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Amphetamine
|
36 Number of positive test results
n=190 Participants
|
67 Number of positive test results
n=225 Participants
|
103 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Barbiturate
|
1 Number of positive test results
n=190 Participants
|
1 Number of positive test results
n=225 Participants
|
2 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Benzodiazepines
|
63 Number of positive test results
n=190 Participants
|
116 Number of positive test results
n=225 Participants
|
179 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Marijuana
|
83 Number of positive test results
n=190 Participants
|
78 Number of positive test results
n=225 Participants
|
161 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Cocaine
|
55 Number of positive test results
n=190 Participants
|
49 Number of positive test results
n=225 Participants
|
104 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Ecstasy (MDMA)
|
8 Number of positive test results
n=190 Participants
|
7 Number of positive test results
n=225 Participants
|
15 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Methamphetamine
|
38 Number of positive test results
n=190 Participants
|
61 Number of positive test results
n=225 Participants
|
99 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Phencyclidine
|
3 Number of positive test results
n=190 Participants
|
0 Number of positive test results
n=225 Participants
|
3 Number of positive test results
n=415 Participants
|
|
Baseline substance use (Urine Drug Screen)
Fentanyl
|
123 Number of positive test results
n=190 Participants
|
140 Number of positive test results
n=225 Participants
|
263 Number of positive test results
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Heavy alcohol use (Females: 3 or more; Males: 4 or more (drinks per day))
|
27 # participants with reported use
n=190 Participants
|
28 # participants with reported use
n=225 Participants
|
55 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Heroin/Fentanyl
|
132 # participants with reported use
n=190 Participants
|
151 # participants with reported use
n=225 Participants
|
283 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Opioid analgesics
|
35 # participants with reported use
n=190 Participants
|
37 # participants with reported use
n=225 Participants
|
72 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Buprenorphine
|
17 # participants with reported use
n=190 Participants
|
11 # participants with reported use
n=225 Participants
|
28 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Methadone
|
6 # participants with reported use
n=190 Participants
|
1 # participants with reported use
n=225 Participants
|
7 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
No opioids (heroin/fentanyl, opioid analgesics, buprenorphine, methadone)
|
7 # participants with reported use
n=190 Participants
|
12 # participants with reported use
n=225 Participants
|
19 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Other amphetamine
|
5 # participants with reported use
n=190 Participants
|
6 # participants with reported use
n=225 Participants
|
11 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Benzodiazepines
|
18 # participants with reported use
n=190 Participants
|
43 # participants with reported use
n=225 Participants
|
61 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Cannabis
|
80 # participants with reported use
n=190 Participants
|
87 # participants with reported use
n=225 Participants
|
167 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Cocaine
|
51 # participants with reported use
n=190 Participants
|
42 # participants with reported use
n=225 Participants
|
93 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Ecstasy (MDMA)
|
10 # participants with reported use
n=190 Participants
|
4 # participants with reported use
n=225 Participants
|
14 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Methamphetamine
|
50 # participants with reported use
n=190 Participants
|
56 # participants with reported use
n=225 Participants
|
106 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Inhalants
|
1 # participants with reported use
n=190 Participants
|
2 # participants with reported use
n=225 Participants
|
3 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Other drugs
|
1 # participants with reported use
n=190 Participants
|
5 # participants with reported use
n=225 Participants
|
6 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 7 days)
Missing
|
21 # participants with reported use
n=190 Participants
|
29 # participants with reported use
n=225 Participants
|
50 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Heavy alcohol use (Females: 3 or more; Males: 4 or more (drinks per day))
|
36 # participants with reported use
n=190 Participants
|
39 # participants with reported use
n=225 Participants
|
75 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Heroin/Fentanyl
|
141 # participants with reported use
n=190 Participants
|
155 # participants with reported use
n=225 Participants
|
296 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Opioid analgesics
|
45 # participants with reported use
n=190 Participants
|
47 # participants with reported use
n=225 Participants
|
92 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Buprenorphine
|
25 # participants with reported use
n=190 Participants
|
16 # participants with reported use
n=225 Participants
|
41 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Methadone
|
11 # participants with reported use
n=190 Participants
|
3 # participants with reported use
n=225 Participants
|
14 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
No opioids (heroine/fentanyl, opioid analgesics, buprenorphine, methadone)
|
2 # participants with reported use
n=190 Participants
|
8 # participants with reported use
n=225 Participants
|
10 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Other amphetamine
|
9 # participants with reported use
n=190 Participants
|
10 # participants with reported use
n=225 Participants
|
19 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Benzodiazepines
|
28 # participants with reported use
n=190 Participants
|
64 # participants with reported use
n=225 Participants
|
92 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Cannabis
|
95 # participants with reported use
n=190 Participants
|
114 # participants with reported use
n=225 Participants
|
209 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Cocaine
|
70 # participants with reported use
n=190 Participants
|
61 # participants with reported use
n=225 Participants
|
131 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Ecstasy (MDMA)
|
18 # participants with reported use
n=190 Participants
|
6 # participants with reported use
n=225 Participants
|
24 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Methamphetamine
|
60 # participants with reported use
n=190 Participants
|
73 # participants with reported use
n=225 Participants
|
133 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Inhalants
|
1 # participants with reported use
n=190 Participants
|
2 # participants with reported use
n=225 Participants
|
3 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Other drugs
|
1 # participants with reported use
n=190 Participants
|
6 # participants with reported use
n=225 Participants
|
7 # participants with reported use
n=415 Participants
|
|
TLFB substance use (at least once in the past 30 days)
Missing
|
21 # participants with reported use
n=190 Participants
|
29 # participants with reported use
n=225 Participants
|
50 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
No use
|
28 # participants with reported use
n=190 Participants
|
35 # participants with reported use
n=225 Participants
|
63 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
Oral
|
3 # participants with reported use
n=190 Participants
|
1 # participants with reported use
n=225 Participants
|
4 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
Nasal
|
54 # participants with reported use
n=190 Participants
|
66 # participants with reported use
n=225 Participants
|
120 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
Smoking
|
25 # participants with reported use
n=190 Participants
|
12 # participants with reported use
n=225 Participants
|
37 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
Injection
|
56 # participants with reported use
n=190 Participants
|
73 # participants with reported use
n=225 Participants
|
129 # participants with reported use
n=415 Participants
|
|
Type of baseline heroin/fentanyl last use from TLFB
Missing
|
21 # participants with reported use
n=190 Participants
|
29 # participants with reported use
n=225 Participants
|
50 # participants with reported use
n=415 Participants
|
|
Type of baseline prescription opioid last use
Nasal
|
18 # participants with reported use
n=190 Participants
|
11 # participants with reported use
n=225 Participants
|
29 # participants with reported use
n=415 Participants
|
|
Type of baseline prescription opioid last use
Smoking
|
1 # participants with reported use
n=190 Participants
|
1 # participants with reported use
n=225 Participants
|
2 # participants with reported use
n=415 Participants
|
|
Type of baseline prescription opioid last use
Injection
|
5 # participants with reported use
n=190 Participants
|
1 # participants with reported use
n=225 Participants
|
6 # participants with reported use
n=415 Participants
|
|
Type of baseline methadone last use
Nasal
|
1 # participants with reported use
n=190 Participants
|
0 # participants with reported use
n=225 Participants
|
1 # participants with reported use
n=415 Participants
|
|
Type of baseline methadone last use
Injection
|
1 # participants with reported use
n=190 Participants
|
0 # participants with reported use
n=225 Participants
|
1 # participants with reported use
n=415 Participants
|
|
Type of baseline buprenorphine last use
Nasal
|
0 # participants with reported use
n=190 Participants
|
0 # participants with reported use
n=225 Participants
|
0 # participants with reported use
n=415 Participants
|
|
Type of baseline buprenorphine last use
Injection
|
0 # participants with reported use
n=190 Participants
|
0 # participants with reported use
n=225 Participants
|
0 # participants with reported use
n=415 Participants
|
|
Substance use disorder
Opioid use disorder
|
189 participants
n=190 Participants
|
224 participants
n=225 Participants
|
413 participants
n=415 Participants
|
|
Substance use disorder
Alcohol use disorder
|
105 participants
n=190 Participants
|
111 participants
n=225 Participants
|
216 participants
n=415 Participants
|
|
Substance use disorder
Amphetamine use disorder
|
85 participants
n=190 Participants
|
119 participants
n=225 Participants
|
204 participants
n=415 Participants
|
|
Substance use disorder
Cannabis use disorder
|
129 participants
n=190 Participants
|
159 participants
n=225 Participants
|
288 participants
n=415 Participants
|
|
Substance use disorder
Cocaine use disorder
|
109 participants
n=190 Participants
|
104 participants
n=225 Participants
|
213 participants
n=415 Participants
|
|
Substance use disorder
Sedative use disorder
|
68 participants
n=190 Participants
|
95 participants
n=225 Participants
|
163 participants
n=415 Participants
|
PRIMARY outcome
Timeframe: Induction Phase: 1-30 daysThe primary goal of the study is to show RP is non-inferior to SP XR-NTX induction method.
Outcome measures
| Measure |
Standard Induction Method
n=190 Participants
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
Rapid Induction Method
n=225 Participants
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
|---|---|---|
|
The Percentage of Patients Who Receive the First XR-NTX Injection (Dichotomous: Did or Did Not Receive First Dose of XR-NTX)
|
68 Participants
|
141 Participants
|
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysPopulation: Only participants who received first injection of XR-NTX were analyzed for days to first injection.
Time to receipt of first injection of XR-NTX from day of admission for participants that receive first injection of XR-NTX.
Outcome measures
| Measure |
Standard Induction Method
n=68 Participants
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
Rapid Induction Method
n=141 Participants
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
|---|---|---|
|
Mean for Time From Admission to First XR-NTX Injection by Treatment Group.
|
14.5 Days
Standard Deviation 3.57
|
7.0 Days
Standard Deviation 1.42
|
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysCraving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1-8 weeksCraving for opioids measured by Visual Analog Scales (VAS). Scale 0-100, 0 no craving and 100 Most intense craving possible
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysOpioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 4 weeksOpioid withdrawal symptoms as measured by the Subjective Opioid Withdrawal Scale (SOWS). Scale 0-64, with the higher score representing greater withdrawal severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysOpioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 4 weeksOpioid withdrawal symptoms as measured by the Clinical Opiate Withdrawal Scale (COWS). Scale 0-59, with the higher score representing greater withdrawal severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysOther depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 8 weeksOther depressive, anxiety, and subacute withdrawal symptoms as measured by the Patient Health Questionnaire-9 (PHQ-9). Scale 0-27, with the higher score representing greater severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Induction Phase: 1-30 daysOther depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 8 weeksOther depressive, anxiety, and subacute withdrawal symptoms as measured by the General Anxiety Disorder-7 (GAD-7). Scale 0-21, with the higher score representing greater severity.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Induction Phase- 1 - 30 days, Post Induction Phase- 1-8 weeksSafety, as measured by targeted safety events and serious adverse events.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 8 weeksEngagement with medical visits and therapy (based on medical management log, XR- NTX dose log, Psychosocial log).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: Week 8Use of medication for opioid use disorder (MOUD) as measured by patient self-report on Timeline Followback (TLFB).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 8 weeksOpioid abstinence, as measured by the Timeline Followback (TLFB) (self-report days using opioids)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: Week 4 and Week 8Opioid abstinence, as measured by the proportion of opioid-positive urine tests.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: 1 - 8 weeksUse of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by self-report
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: Week 4 and Week 8Use of alcohol and other drugs of abuse (e.g., cocaine, other stimulants, cannabis, benzodiazepines), by urine drug screens.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Post Induction Phase: Week 4 and Week 8Retention in the trial to receive the second and the third XR-NTX injections.
Outcome measures
Outcome data not reported
Adverse Events
Standard Induction Method
Serious events: 7 serious events
Other events: 7 other events
Deaths: 1 deaths
Rapid Induction Method
Serious events: 12 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Standard Induction Method
n=190 participants at risk
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
Rapid Induction Method
n=225 participants at risk
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
|---|---|---|
|
Injury, poisoning and procedural complications
Overdose
|
0.53%
1/190 • 70 weeks
|
1.3%
3/225 • 70 weeks
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Psychiatric disorders
Suicidal Ideation
|
0.00%
0/190 • 70 weeks
|
0.89%
2/225 • 70 weeks
|
|
Psychiatric disorders
Suicide Attempt
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Psychiatric disorders
Alcohol Withdrawal Syndrome
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Infections and infestations
Sepsis
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Infections and infestations
Pneumonia
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Infections and infestations
COVID-19
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Infections and infestations
Abscess (neck)
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Nervous system disorders
Drug withdrawal convulsions
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Nervous system disorders
Depressed level of consciousness
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
General disorders
Death
|
0.53%
1/190 • 70 weeks
|
0.00%
0/225 • 70 weeks
|
|
Gastrointestinal disorders
Enteritis
|
0.00%
0/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
Other adverse events
| Measure |
Standard Induction Method
n=190 participants at risk
The Standard Method (13-day long) includes 5-days of buprenorphine taper followed by 7-day washout period
Standard Induction Procedure (SP): SP includes stabilization on buprenorphine (6-8 mg) on Day 1 followed by a taper over the subsequent 4 days. After the completion of buprenorphine taper, participants will enter a washout period of at least 8 days. On the last day of the washout period, participants will be evaluated for eligibility to receive XR-NTX injection. Once found eligible, an XR-NTX injection will be given.
|
Rapid Induction Method
n=225 participants at risk
The Rapid Method includes one day of buprenorphine followed by a day of washout and 3-4 days of oral naltrexone titration with adjunctive medications
Rapid Induction Procedure (RP): RP includes 1 day of buprenorphine 6-8 mg, followed by a day of washout and 4 days of oral naltrexone titration. If the participant is able to tolerate the last dose of the naltrexone titration, an XR-NTX injection will be given
|
|---|---|---|
|
Injury, poisoning and procedural complications
Fall Event
|
0.53%
1/190 • 70 weeks
|
3.6%
8/225 • 70 weeks
|
|
Psychiatric disorders
Acute change in mental status
|
0.53%
1/190 • 70 weeks
|
0.44%
1/225 • 70 weeks
|
|
Psychiatric disorders
Acute mental complication likely exacerbated by the stress of withdrawal
|
2.6%
5/190 • 70 weeks
|
5.8%
13/225 • 70 weeks
|
|
Psychiatric disorders
Acute psychiatric symptoms
|
0.00%
0/190 • 70 weeks
|
3.6%
8/225 • 70 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place