Trial Outcomes & Findings for Prescription Opioid Addiction Treatment Study (POATS) (NCT NCT00316277)

NCT ID: NCT00316277

Last Updated: 2013-02-06

Results Overview

In Phase 1, successful outcome was defined as completing week 12 with self-reported opioid use on no more than 4 days in a month, absence of 2 consecutive opioid-positive urine test results, no additional substance use disorder treatment (other than self-help), and no more than 1 missing urine sample during the 12 weeks.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 653 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2013-02-06

Participant Flow

653 treatment-seeking outpatients dependent on prescription opioids across 10 U.S. sites.

Participant milestones

Measure	Buprenorphine/Nx With EMM All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
Phase 1 (12 Weeks) STARTED	329	324
Phase 1 (12 Weeks) COMPLETED	19	24
Phase 1 (12 Weeks) NOT COMPLETED	310	300
Phase 2 (24 Weeks) STARTED	180	180
Phase 2 (24 Weeks) COMPLETED	161	161
Phase 2 (24 Weeks) NOT COMPLETED	19	19

Reasons for withdrawal

Measure	Buprenorphine/Nx With EMM All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
Phase 1 (12 Weeks) Lost to Follow-up	88	75
Phase 1 (12 Weeks) Investigator-initiated termination	2	0
Phase 1 (12 Weeks) Eligible for Phase 2	220	225
Phase 2 (24 Weeks) Lost to Follow-up prior to wk 13	19	18
Phase 2 (24 Weeks) Discontinued intervention (jailed)	0	1

Baseline Characteristics

Prescription Opioid Addiction Treatment Study (POATS)

Baseline characteristics by cohort

Measure	Buprenorphine/Nx With EMM n=329 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=324 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.	Total n=653 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	329 Participants n=5 Participants	324 Participants n=7 Participants	653 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	32.9 years STANDARD_DEVIATION 10.1 • n=5 Participants	33.5 years STANDARD_DEVIATION 10.3 • n=7 Participants	33.2 years STANDARD_DEVIATION 10.2 • n=5 Participants
Sex: Female, Male Female	125 Participants n=5 Participants	136 Participants n=7 Participants	261 Participants n=5 Participants
Sex: Female, Male Male	204 Participants n=5 Participants	188 Participants n=7 Participants	392 Participants n=5 Participants
Region of Enrollment United States	329 participants n=5 Participants	324 participants n=7 Participants	653 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: 653 study participants randomized to Phase 1 were included in analysis.

In Phase 1, successful outcome was defined as completing week 12 with self-reported opioid use on no more than 4 days in a month, absence of 2 consecutive opioid-positive urine test results, no additional substance use disorder treatment (other than self-help), and no more than 1 missing urine sample during the 12 weeks.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=329 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=324 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition at End of Phase 1	19 participants Interval 3.5 to 8.9	24 participants Interval 4.8 to 10.8

PRIMARY outcome

Timeframe: 12 weeks in Phase 2 period (i.e., 24 weeks into the study)

Population: 360 participants randomized to Phase 2 were included in the analysis.

In phase 2, successful outcome was defined as abstaining from opioids during week 12 (the final week of buprenorphine-naloxone stabilization) and during at least 2 of the previous 3 weeks (weeks 9-11). This outcome measure required substantial improvement but not complete abstinence.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=180 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=180 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition, Phase 2 End of Treatment	93 participants	84 participants

SECONDARY outcome

Timeframe: 24 weeks in Phase 2 period (i.e., 36 weeks into the study)

Population: 360 participants randomized to Phase 2 were included in the analysis.

A planned secondary outcome, successful outcome at week 24, that is, 8 weeks after completion of buprenorphine-naloxone taper, was defined the same as at week 12 of Phase 2, that is abstinent from opioids during week 24 and at least 2 of the previous 3 weeks.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=180 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=180 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants Attaining Successful Opioid Use Outcome by Counseling Condition Phase 2, 8-week Posttreatment Follow-up	18 participants	13 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: 379 identified as having chronic pain at baseline in Phase 1.

As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain "other than everyday kinds of pain" excluding withdrawal-related pain, for at least 3 months.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=379 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=274 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 1 by Chronic Pain Condition	30 participants	13 participants

SECONDARY outcome

Timeframe: 12 weeks

As a planned secondary analysis, we examined the impact of the two Phase 1 stratification variables on the primary end points. Patients were designated at baseline as having current chronic pain if they reported pain "other than everyday kinds of pain" excluding withdrawal-related pain, for at least 3 months.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=149 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=211 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants Attaining Successful Opioid Use Outcomes in Phase 2 by Chronic Pain Condition	79 participants	98 participants

SECONDARY outcome

Timeframe: 12 weeks

Population: Participants randomized to Phase 1 were stratified by two variables: current chronic pain and lifetime heroin use.

As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=150 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=503 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 1	9 participants	34 participants

SECONDARY outcome

Timeframe: 12 weeks

As a planned secondary analysis, we examined the impact of the two phase 1 stratification variables on the primary outcome.

Outcome measures

Measure	Buprenorphine/Nx With EMM n=100 Participants All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=260 Participants All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
The Number of Participants With and Without Any Lifetime Use of Heroin Attaining Successful Opioid Use Outcomes in Phase 2	37 participants	140 participants

Adverse Events

Buprenorphine/Nx With EMM

Serious events: 6 serious events

Other events: 277 other events

Deaths: 0 deaths

Buprenorphine/Nx With SMM

Serious events: 5 serious events

Other events: 265 other events

Deaths: 0 deaths

Serious adverse events

Measure	Buprenorphine/Nx With EMM n=329 participants at risk All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=324 participants at risk All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
Psychiatric disorders Suicidal Ideation	0.00% 0/329 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.62% 2/324 • Number of events 2 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Psychiatric disorders Anxiety	0.00% 0/329 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.31% 1/324 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Gastric Ulcer	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Pancreatitis	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Infections and infestations Pneumonia	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Injury, poisoning and procedural complications Accidental Overdose	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Nervous system disorders Grand Mal Convulsion	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Renal and urinary disorders Urinary Retention	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/329 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.31% 1/324 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Reproductive system and breast disorders Ovarian Torsion	0.00% 0/329 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.31% 1/324 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Metabolism and nutrition disorders Dehydration	0.00% 0/329 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.31% 1/324 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Metabolism and nutrition disorders Hyperglycaemia	0.30% 1/329 • Number of events 1 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	0.00% 0/324 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.

Other adverse events

Measure	Buprenorphine/Nx With EMM n=329 participants at risk All study participants received buprenorphine-naloxone. This treatment group (Buprenorphine/Naloxone with Enhanced Medical Management) consisted of Standard Medical Management office visits with study physicians certified to prescribe buprenorphine and opioid drug counseling from a trained substance abuse or mental health professional.	Buprenorphine/Nx With SMM n=324 participants at risk All study participants received buprenorphine-naloxone medication. This treatment group (buprenorphine-naloxone with Standard Medical Management) consisted of office visits with study physicians certified to prescribe buprenorphine.
Nervous system disorders Headache	32.8% 108/329 • Number of events 130 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	25.6% 83/324 • Number of events 98 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Constipation	12.8% 42/329 • Number of events 42 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	19.1% 62/324 • Number of events 64 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Nausea	14.0% 46/329 • Number of events 48 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	11.7% 38/324 • Number of events 42 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Psychiatric disorders Insomnia	11.9% 39/329 • Number of events 40 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	14.5% 47/324 • Number of events 48 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Vomiting	8.2% 27/329 • Number of events 32 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	9.3% 30/324 • Number of events 32 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Psychiatric disorders Anxiety	9.1% 30/329 • Number of events 30 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	7.4% 24/324 • Number of events 25 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Gastrointestinal disorders Toothache	5.8% 19/329 • Number of events 19 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	6.8% 22/324 • Number of events 25 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Infections and infestations Nasopharyngitis	6.4% 21/329 • Number of events 21 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	4.6% 15/324 • Number of events 17 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
Musculoskeletal and connective tissue disorders Back Pain	4.9% 16/329 • Number of events 16 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	7.4% 24/324 • Number of events 26 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.
General disorders Fatigue	5.5% 18/329 • Number of events 18 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.	5.2% 17/324 • Number of events 18 • Adverse Events were captured beginning at the time of randomization and every subsequent research visit.

Additional Information

Roger D. Weiss, M.D.

McLean Hospital/Harvard Medical School

Phone: 617-855-2242

Email: rweiss@mclean.harvard.edu

Results disclosure agreements

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