Starting Treatment With Agonist Replacement Therapies (START)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00315341 |
Recruitment Status :
Completed
First Posted : April 18, 2006
Results First Posted : January 6, 2017
Last Update Posted : January 6, 2017
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Condition or disease | Intervention/treatment | Phase |
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Opiate-related Disorders | Drug: Buprenorphine/naloxone Drug: Methadone | Phase 4 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 1269 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Starting Treatment With Agonist Replacement Therapies (START) |
Study Start Date : | April 2006 |
Actual Primary Completion Date : | August 2010 |
Actual Study Completion Date : | August 2010 |

Arm | Intervention/treatment |
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Experimental: Buprenorphine/Nx
For the BUP/NX group, all participants will receive up to 16 mg BUP/4 mg NX on day 1 and up to 32 mg BUP/8 mg NX on day 2. It is recommended that dose changes be made in 2 to 8 mg buprenorphine increments, with the range of allowable daily doses between 2 mg and 32 mg starting on day 3 and thereafter according to clinical impression and depending upon the participant's clinical need. Investigators are encouraged to dose adequately to decrease craving and to obtain negative urine toxicology specimens.
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Drug: Buprenorphine/naloxone
Participants receive up to 16 mg BUP/4 mg NX on day 1 and up to 32 mg BUP/8 mg NX on day 2. It is recommended that dose changes be made in 2 to 8 mg increments, with the range of allowable daily doses between 2 mg and 32 mg starting on day 3 and thereafter according to clinical impression and depending upon the participant's clinical need. |
Active Comparator: Methadone
For the MET group, all participants will receive a maximum of 30 mg for the first dose and a maximum of 40 mg on Day 1. It is recommended that participants receive a dose on day 2 that is 10 mg higher than their total day 1 dose, and a dose on day 3 that is 10 mg higher than their total day 2 dose, unless, in the clinical judgment of the physician, a slower induction is needed. Doses will be adjusted on Day 4 and thereafter according to clinical impression and depending upon the participant's clinical need with no specific upper limit. Investigators are encouraged to dose adequately to decrease craving and to obtain negative urine toxicology specimens.
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Drug: Methadone
Participants will receive a maximum of 30 mg for the first dose and a maximum of 40 mg on Day 1. It is recommended that participants receive a dose on day 2 that is 10 mg higher than their total day 1 dose, and a dose on day 3 that is 10 mg higher than their total day 2 dose, unless, in the clinical judgment of the physician, a slower induction is needed. Doses will be adjusted on Day 4 and thereafter according to clinical impression and depending upon the participant's clinical need with no specific upper limit. |
- Hepatic Safety [ Time Frame: 24 Weeks ]
Participants were categorized according liver transaminase (ALT, AST) levels in blood comparing the baseline sample to any and all subsequent samples in the following manner:
A: both ALT and AST started at less than or equal to two times the ULN and remained at two times or less ULN throughout the study
B: either ALT or AST started at less than or equal to 2 x ULN and at any point in study exceeded 2 x ULN
C: Either ALT or AST started > 2 x ULN, decreased (both ALT and AST) to < 2 x ULN, and remained < 2 x ULN
D: Either ALT or AST started > 2 x ULN and remained above 2 x ULN throughout the study

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Were age 18 years or older,
- Met DSM-IV-TR criteria for opioid dependence,
- Were in good general health, or, in case of a medical/psychiatric condition requiring ongoing treatment, were under the care of a physician willing to continue participant's medical management and cooperate with study physicians,
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For female participants, use of one of the following acceptable methods of birth control:
- oral contraceptives
- barrier (diaphragm or condom) with spermicide
- IUD
- intrauterine progesterone contraceptive system
- levonorgestrel implant
- medroxyprogesterone acetate contraceptive injection
- contraceptive transdermal patch
- hormonal vaginal contraceptive ring
- surgical sterilization
- complete abstinence from sexual intercourse
- Able to read and verbalize understanding of the study and voluntarily sign study informed consent form.
Exclusion Criteria:
- ALT or AST values > 5 times the upper limit of normal as per testing laboratory range criteria,
- ALP values >3 times the upper limit of normal per testing laboratory criteria,
- Any documented past or present history of ascites, presence of esophageal or gastric varices, hepatic encephalopathy or other signs of significant liver disease as indicated by a Model for Endstage Liver Disease score (Kamath et al., 2001) of ≥11,
- Total bilirubin > 2.0 mg/dl (participants with documented Gilbert's syndrome were not excluded based on this criterion),
- Prothrombin time more than 3 seconds prolonged,
- Albumin level less than 2.5 g/dl,
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Any cardiopathy or risk factor listed below without evidence of a normal ECG* with report performed within 6 months prior to first study medication dose,
- Congestive heart failure
- Left ventricular hypertrophy
- Bradycardia
- Hereditary QT prolongation
- Uncorrected electrolyte imbalance
- Concomitant medications that are known to have a risk of QT interval prolongation; refer to Appendix D for a list of medications.
Note: The list was not all-inclusive.
*An ECG was abnormal if one or more of the following occurred:
Significant ST segment abnormalities:
- ST segment elevations in two or more continuous leads of > 0.1 mV
- ST segment depression of greater than 1 mm that are flat or down-sloping at 80 msec after the J point ST segment abnormalities identified as "non-specific" are acceptable. If a potential participant's ECG indicated ST segment elevations or depression consistent with ischemia, the physician obtained a medical history of cardiac symptoms and referred the participant for evaluation.
Conduction abnormalities:
- Mobitz II 2nd degree or 3rd degree heart block
- Atrial fibrillation, atrial flutter, or any non-sinus tachyarrhythmia
- Three or more consecutive ectopic ventricular complexes at a rate of > 100 per minute.
- QTc greater than 450 msec in men and 480 msec in women
Repolarization abnormalities:
• Acute medical condition that would make participation, in the opinion of the study physician, medically hazardous (e.g., unstable pancreatic, cardiovascular or renal disease, significant anemia)
- Known allergy or sensitivity to BUP, naloxone or MET or to any of the inactive ingredients in the study medications (including lactose, mannitol, cornstarch, povidone K30, citric acid, sodium citrate, FD&C Yellow No.6 color, magnesium stearate, Acesulfame K sweetener)
- Known diagnosis of acute psychosis, severe depression or imminent suicide risk as determined via clinical interview by study physician or surrogates
- DSM-IV diagnosis of dependence on alcohol requiring immediate medical attention.
- DSM-IV diagnosis of dependence on benzodiazepines requiring immediate medical attention
- DSM-IV diagnosis of dependence on other depressants, or stimulants requiring immediate medical attention
- Participation in an investigational drug study within the past 30 days
- Treatment with MET, BUP/NX, or BUP for more than 15 of the past 30 days (illicit use of these medications is allowed)
- Pending legal action that could prohibit study participation
- Unable or unwilling to comply with study requirements
- Unable or unwilling to remain in the local area for duration of treatment
- Poor venous access such that venipuncture could not be accomplished from a vein in an extremity during eligibility
- Pregnant or lactating (females only)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00315341
United States, California | |
Matrix Institute | |
Los Angeles, California, United States, 90016 | |
Bi-Valley Medical Clinic INC. | |
Sacramento, California, United States, 95816 | |
BAART; Turk Street Clinic | |
San Francisco, California, United States, 94102 | |
United States, Connecticut | |
Hartford Dispensary | |
Hartford, Connecticut, United States, 06120 | |
CT Counseling Centers | |
Waterbury, Connecticut, United States, 06705 | |
United States, New York | |
Addiction Research & Treatment Corp | |
Brooklyn, New York, United States, 11201 | |
United States, Oregon | |
CODA-Research | |
Portland, Oregon, United States, 97214 | |
United States, Pennsylvania | |
NET Steps | |
Philadelphia, Pennsylvania, United States, 19137 | |
United States, Washington | |
Evergreen Treatment Services | |
Seattle, Washington, United States, 98134 |
Principal Investigator: | Walter Ling, M.D. | University of California, Los Angeles | |
Principal Investigator: | Andrew Saxon, M.D. | University of Washington |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Walter Ling, Principal Investigator, University of California, Los Angeles |
ClinicalTrials.gov Identifier: | NCT00315341 |
Other Study ID Numbers: |
NIDA-CTN-0027 U10DA013045 ( U.S. NIH Grant/Contract ) |
First Posted: | April 18, 2006 Key Record Dates |
Results First Posted: | January 6, 2017 |
Last Update Posted: | January 6, 2017 |
Last Verified: | November 2016 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Buprenorphine Methadone Buprenorphine, Naloxone Drug Combination Naloxone Analgesics, Opioid Narcotics Central Nervous System Depressants |
Physiological Effects of Drugs Analgesics Sensory System Agents Peripheral Nervous System Agents Narcotic Antagonists Antitussive Agents Respiratory System Agents |