Trial Outcomes & Findings for Buprenorphine Maintenance vs. Detoxification in Prescription Opioid Dependence (NCT NCT00555425)

NCT ID: NCT00555425

Last Updated: 2019-01-14

Results Overview

Urinalysis based on scheduled weekly urine screenings during treatment period

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 113 participants
• Primary outcome timeframe: 18 weeks
• Results posted on: 2019-01-14

Participant Flow

289 Patients underwent assessment for eligibility, 29 did not meet inclusion criteria, 132 lost contact or chose other treatment, and 15 did not complete induction

Participant milestones

Measure	Taper Condition Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Overall Study STARTED	57	56
Overall Study COMPLETED	6	37
Overall Study NOT COMPLETED	51	19

Reasons for withdrawal

Measure	Taper Condition Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Overall Study Missed Medication > 1 wk	34	15
Overall Study Missed 3 physician management visits	1	0
Overall Study Met criteria for protective transfer	16	3
Overall Study Became pregnant and transferred care	0	1

Baseline Characteristics

Buprenorphine Maintenance vs. Detoxification in Prescription Opioid Dependence

Baseline characteristics by cohort

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.	Total n=113 Participants Total of all reporting groups
Age, Continuous	30.3 years STANDARD_DEVIATION 8.8 • n=5 Participants	30.5 years STANDARD_DEVIATION 9.8 • n=7 Participants	30.4 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	25 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	31 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	53 Participants n=5 Participants	52 Participants n=7 Participants	105 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	56 Participants n=5 Participants	52 Participants n=7 Participants	108 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 18 weeks

Urinalysis based on scheduled weekly urine screenings during treatment period

Outcome measures

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Illicit Opioid Use	35.2 percent of opioid negative urine samples Interval 26.2 to 44.2	53.2 percent of opioid negative urine samples Interval 44.3 to 62.0

SECONDARY outcome

Timeframe: 18 weeks

>= 2 consecutive weeks of daily illicit opioid use and opioid positive urine samples after completion of the first 6 weeks of the study

Outcome measures

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Proportion of Patients Protectively Transferred	16 participants	3 participants

SECONDARY outcome

Timeframe: 18 weeks

Mean number of days from randomization to last clinical contact

Outcome measures

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Retention in Treatment	57.5 number of days Interval 47.0 to 59.9	98.7 number of days Interval 88.0 to 109.4

SECONDARY outcome

Timeframe: 18 weeks

As measured by the percent of provided urines positive for cocaine

Outcome measures

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Reduction in Cocaine Use	11.5 percent of cocaine positive urines Standard Deviation 25.9	11.1 percent of cocaine positive urines Standard Deviation 23.5

SECONDARY outcome

Timeframe: Baseline and 18 weeks

As measured by the AIDS Risk Inventory. The AIDS Risk Inventory (ARI) is a 166 item structured interview that assesses the number and frequency of drug-related and sexual risk behaviors in the preceding 3 months. Calculation of the ARI total score is based on the frequency of occurrence of a given behavior and on the recency of this behavior, with recency being weighted more than a life-time occurrence of the same behavior. Higher values are associated with greater risk of HIV transmission (worse).

There are 10 subscales comprised of between 8 and 24 items. Subscales scores are based on the sum of the individual items and the overall ARI total score is the sum of the subscales.

Scores can range from 0 to 350, although among opioid dependent patients most values are below 100 with means between 50 and 60 depending on characteristics of the patients and treatment status.

Outcome measures

Measure	Taper Condition n=57 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=56 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Changes in HIV Risk Baseline	66.7 units on a scale Standard Deviation 25.6	67.6 units on a scale Standard Deviation 25.7
Changes in HIV Risk 18 weeks	74.5 units on a scale Standard Deviation 19.4	74.4 units on a scale Standard Deviation 18

SECONDARY outcome

Timeframe: 18 weeks

Population: Results are provided on those individuals who completed this assessment

Patient satisfaction as measured by survey. Primary Care Buprenorphine Satisfaction Scale (PCBSS). Comprises of 19 items evaluating satisfaction with staff expertise, concern, and responsiveness. Range of scores from 15-95. I higher score indicates greater satisfaction.

Outcome measures

Measure	Taper Condition n=37 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=45 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Patient Satisfaction	78.7 units on a scale Interval 73.9 to 83.4	79.9 units on a scale Interval 75.2 to 84.7

SECONDARY outcome

Timeframe: 18 weeks

Population: Results are provided on those individuals who completed this assessment

Measured by the SF-36 overall transformed measure. In the SF-36 all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively.

Outcome measures

Measure	Taper Condition n=47 Participants Buprenorphine/naloxone detoxification (Dtx) is identical to Mtn for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Buprenorphine/naloxone. Behavioral: Buprenorphine/naloxone detoxification (Dtx): Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Dtx, the dosage of Bup will be tapered to zero over the next 3 weeks, and patients will not receive additional Bup for the remainder of the study. Dtx patients will be offered thrice-weekly DC beginning during the taper and naltrexone will be offered 7 days following the last dose of Bup.	Maintenance Condition n=54 Participants Buprenorphine/naloxone maintenance (Mtn) is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Behavioral: Buprenorphine/naloxone maintenance (Mtn): Mtn is designed to reflect usual care by primary care physicians and includes weekly drug counseling (DC) and referral to ancillary services. Dtx and Mtn will be identical for the first 4 weeks (stabilization) following randomization. In Mtn, Bup will continue unchanged for the remainder of the study.
Health Status Baseline	67.2 units on a scale Standard Deviation 20.4	67.6 units on a scale Standard Deviation 18.6
Health Status In-Treatment	68.7 units on a scale Standard Deviation 30.5	66.6 units on a scale Standard Deviation 21.9

Adverse Events

Taper Condition

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Maintenance Condition

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. David Fiellin

Yale University

Phone: 203-688-2471

Email: david.fiellin@yale.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place