Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in SingaporePhase 4NCT01675648
Lofexidine for Inpatient Opiate Detox in Singapore
A Phase 4 study testing Lofexidine and Diazepam in people with Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in Singapore, run by Institute of Mental Health, Singapore at 1 site in Singapore.
Trial summary
In Singapore, opiate substitution medication e.g. methadone is only licensed for use with specific population. The standard treatment is one week of detoxification assisted with diazepam and symptomatic treatment followed by one week of rehabilitation. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in Singapore
- What is being tested?
- Lofexidine and Diazepam
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 112 participants
- Where
- 1 siteSingapore
- Study dates
- Aug 2012to Jul 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients who meet the DSM-IV criteria for a diagnosis of opiate dependence (as diagnosed by a NAMS psychiatrist).
- Individuals are voluntarily undergoing inpatient opiate withdrawal treatment at the National Addictions Management Service (NAMS).
- Agreeable to participating in the clinical trial and will provide written consent.
- Males or females who are between the ages of 21-55 years. The lower limit of 21 years is in place because of lack of data on younger populations. The upper limit is set at 55 years as the likelihood of having co-morbid physical health problems is greater.
- Individuals who have a positive urine screen for the presence of opiates (routinely given on first visit to outpatient clinic).
Who cannot join
- Are investigator site personnel directly affiliated with this study and their immediate families, immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
- Are currently enrolled in, or discontinued within the last 30 days from another clinical trial or medical research judged not to be scientifically or medically compatible with this study.
- A history of allergy/sensitivity to clonidine, lofexidine, imidazole derivatives (e.g. clotrimazole, antifungal) or alpha-2-adrenergic medications.
- Co-dependency on alcohol, benzodiazepines or any other drug that would require detoxification.
- A history of major physical illness (cardiovascular disease, cerebrovascular disease, renal impairment, liver disease, epilepsy, symptomatic HIV, Hepatitis B and/or C).
- Patients with major psychiatric illness (e.g. psychotic disorders, major depression).
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- Patients prescribed analgesic*(*: Opioid analgesic and similar narcotic analgesics), antihypertensive, antiarrhythmic, or antiretroviral medication.
- Baseline BP > 140/90 mmHg or < 85/55mmHg, and/or baseline PR <55beats/min.
- Significant abnormal finding from blood tests (FBC, LFT, Renal function) and ECG during screening.
- Pregnant or breast feeding.
- Patients are receiving and not willing to stop the drugs which may cause prolong QT interval and hypotension while using concomitant with Lofexidine, e.g. thioridazine, chlorpromazine, tricyclic antidepressants.
Trial locations and contacts
1 site in 1 country.
Singapore1 site
National Addictions Management Service, Institute of Mental Health, Singapore
Singapore, Singapore, 539747
About this study
Official title: A Double-blind Randomised Controlled Clinical Trial of Lofexidine Versus Diazepam in the Management of the Opioid Withdrawal Syndrome During Inpatient Detoxification in Singapore
In Singapore, opiate substitution medication e.g. methadone is only licensed for use with specific population. The standard treatment is one week of detoxification assisted with diazepam and symptomatic treatment followed by one week of rehabilitation. However, diazepam is highly addictive and widely abused among heroin users and pharmacologically, does not reduce the physical and psychological craving for opioids which can trigger relapse. Many opiate patients undergoing inpatient detoxification leave prematurely (i.e. PID: patient initiated discharge) because of the severity of unpleasant withdrawal symptoms. The purpose of the study is to establish an alternative medication to reduce opiate withdrawal symptoms for use in Singapore by evaluating the clinical efficacy of Lofexidine versus Diazepam in the management of the opiate withdrawal syndrome during inpatient detoxification.
Read the detailed description
Study Design: This is a randomized, double-blind (double-dummy design) phase IV clinical trial. Patients will be receiving 10 days of Lofexidine plus Diazepam placebo or Diazepam plus Lofexidine placebo. All the patients are expected to complete the 2-weeks inpatient detoxification programme at the NAMS ward. Up to 122 patients (61 in each randomized arm) will be enrolled into the study to ensure that at least 43 patients in each arm complete Day 4 of study treatment programme.
Efficacy Assessments: The primary efficacy outcome measure will be the Objective Opiate Withdrawal Scale (OOWS) scores (range = 0-13) on Day 3 and Day 4 of the treatment phase. The second efficacy outcome measure will be the Short Opiate Withdrawal Scale (SOWS), Opiate Craving visual analogue scale and Pupil size on Day 3 and Day 4, time to dropout (length of stay on the ward) and emotional/psychological symptoms measured every 3 days. Our expected study outcomes are as following:
- Significantly lower mean scores on the Objective Opiate Withdrawal Scale (OOWS) on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower mean scores on the Subjective experience of opiate withdrawal scale (SOWS)on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly larger pupil size on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower mean craving score on the Visual Analogue Scale on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly longer stay (days) on the ward among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower anxiety and depression score on the MAP among patients in the lofexidine arm relative to those in the benzodiazepine arm
Safety Assessment and Monitoring: After signing the informed consent, the subject will undergo screening assessments to determine eligibility for study enrollment; the screen tests include FBC, LFT, Renal function and 12-lead ECG, and urine pregnancy test if female. A complete physical examination will be performed on the first day of screening. From Day 1 till discharge, Vital Signs (e.g. pulse rate, body temperature, blood pressure and respiratory rate) will be closely monitored by the study nurses at the ward, i.e. immediately prior to each lofexidine dose and in addition, 2 hours after the first dose of each dosing day. Should patients show signs of hypotension, the nurse will inform the investigators and they will determine whether or not it is necessary to terminate the patients' participation in the trial. Patients will be required to repeat a 12-lead ECG test when they complete the study or if they drop out of the study. If there is any significant finding from the repeat ECG, it will be followed through by the investigators until resolved. All the adverse events will be documented and followed through until resolved during the study period. The Regular Study Safety Reports inclusive of patients' recruitment, AE/SAE will be generated periodically and sent to an Independent Date \& Safety Monitoring Committee (DSMC) for review, the DSMC comprise addiction medicine experts from outside of IMH. Individual patients or the entire study will be discontinued if there is any major safety finding.
Sample Size and Statistical methods: The estimate of 122 subjects (61 per group) for the sample size is based on the following assumptions - mean (SE) OOWS scores on day 4 of 2.4 (0.4000) and 3.9 (2.7713) for the lofexidine and diazepam groups respectively (which implies an expected absolute treatment effect of 1.5), a power of 80%, and allowing for 30% of the patients dropping out before their evaluation on day 4. Thirty percent dropout implies that 86 subjects (43 per group) are required to evaluate the benefit of lofexidine over diazepam. The primary efficacy analysis will be done using the ITT dataset and the safety profile will be described using the safety dataset. All analysis will be conducted by independent statisticians (SCRI).
- Being tested
- Lofexidine, Diazepam, Placebo for Lofexidine, Placebo for Diazepam
- Keywords
- Opiate dependent, inpatient detoxification
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LofexidineDrug
Also called BritLofex 0.2mg
DiazepamDrug
Also called Apo-Diazepam 5mg and 2mg
Placebo for LofexidineDrug
Placebo for DiazepamDrug
| Study group | Role | What they receive |
|---|---|---|
| Lofexidine & Diazepam Placebo | Experimental | Initial Lofexidine dosage starts from 0.8mg per day, it will be gradually increased by increments of 0.4 to 0.8mg per day up to a maximum of 2.2mg daily. After 3 peak dose days, the dosage will be gradually decreased by 0.2 to 0.6mg per day till to 0.2mg of the last lofexidine dosage in Day 10.
The Diazepam placebo will be administrated to the patients with the same frequency, time and number tablets of diazepam in the active comparator arm. Receives: Drug: Lofexidine; Drug: Placebo for Diazepam |
| Diazepam & Lofexidine Placebo | Active comparator | The initial dosage of Diazepam is 10 mg per day on Day 1\&2, the dosage will be increased to 15 mg per day on Day 3\&4, subsequently decreased to 10mg per day on Day 5, 5mg per day on Day 6\&7, 2mg per day on Day 8\&9\&10.
The Lofexidine placebo will be administrated to the patients with the same frequency, time and number tablets of lofexidine in the experimental arm. Receives: Drug: Diazepam; Drug: Placebo for Lofexidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate differences in OOWS (Objective Opiate Withdrawal Scale)
Measured: on day 3 and day 4 during inpatient dotex
Secondary outcomes (5)
To evaluate differences in SOWS (Short Opiate Withdrawal Scale)
Measured: on day 3 and day 4 during inpatient detox
To evaluate differences in pupil sizes
Measured: on days 3 and 4 of inpatient detox
To evaluate differences in craving on the Visual Analogue Scale
Measured: on days 3 and 4 of inpatient detox
To evaluate differences in time to drop-out (length of stay on the ward)
Measured: time to drop-out
To evaluate differences in emotional/psychological symptoms
Measured: every 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2012 (estimated)
- Study startAug 2012
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in SingaporeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 112 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institute of Mental Health, Singapore
- Sponsor type
- University, hospital or other
- Collaborators
- Singapore Clinical Research Institute
- Responsible party
- Principal investigator, Dr. Guo Song, Institute of Mental Health, Singapore
- Investigators
- Song Guo, Ph.D, Principal investigator, NAMS IMH Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01675648
- Sponsor's protocol ID
- Lofex00428
- Status last verified
- Aug 2015
- First submitted
- 16 Aug 2012
- Last updated
- 28 Aug 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Guo S, Manning V, Yang Y, Koh PK, Chan E, de Souza NN, Assam PN, Sultana R, Wijesinghe R, Pangjaya J, Kandasami G, Cheok C, Lee KM, Wong KE. Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore. J Subst Abuse Treat. 2018 Aug;91:1-11. doi: 10.1016/j.jsat.2018.04.012. Epub 2018 Apr 25.
PubMed 29910009
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind Randomised Controlled Clinical Trial of Lofexidine Versus Diazepam in the Management of the Opioid Withdrawal Syndrome During Inpatient Detoxification in Singapore
- ClinicalTrials.gov ID
- NCT01675648
- Acronym / sponsor ID
- Lofex00428
- Keywords
- Opiate dependent, inpatient detoxification
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Institute of Mental Health, SingaporeUniversity, hospital or other
- Collaborators
- Singapore Clinical Research Institute
- Study start
- Aug 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 30 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In Singapore, opiate substitution medication e.g. methadone is only licensed for use with specific population. The standard treatment is one week of detoxification assisted with diazepam and symptomatic treatment followed by one week of rehabilitation. However, diazepam is highly addictive and widely abused among heroin users and pharmacologically, does not reduce the physical and psychological craving for opioids which can trigger relapse. Many opiate patients undergoing inpatient detoxification leave prematurely (i.e. PID: patient initiated discharge) because of the severity of unpleasant withdrawal symptoms. The purpose of the study is to establish an alternative medication to reduce opiate withdrawal symptoms for use in Singapore by evaluating the clinical efficacy of Lofexidine versus Diazepam in the management of the opiate withdrawal syndrome during inpatient detoxification.
Detailed description
Study Design: This is a randomized, double-blind (double-dummy design) phase IV clinical trial. Patients will be receiving 10 days of Lofexidine plus Diazepam placebo or Diazepam plus Lofexidine placebo. All the patients are expected to complete the 2-weeks inpatient detoxification programme at the NAMS ward. Up to 122 patients (61 in each randomized arm) will be enrolled into the study to ensure that at least 43 patients in each arm complete Day 4 of study treatment programme.
Efficacy Assessments: The primary efficacy outcome measure will be the Objective Opiate Withdrawal Scale (OOWS) scores (range = 0-13) on Day 3 and Day 4 of the treatment phase. The second efficacy outcome measure will be the Short Opiate Withdrawal Scale (SOWS), Opiate Craving visual analogue scale and Pupil size on Day 3 and Day 4, time to dropout (length of stay on the ward) and emotional/psychological symptoms measured every 3 days. Our expected study outcomes are as following:
- Significantly lower mean scores on the Objective Opiate Withdrawal Scale (OOWS) on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower mean scores on the Subjective experience of opiate withdrawal scale (SOWS)on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly larger pupil size on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower mean craving score on the Visual Analogue Scale on day 3 and 4 of detox among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly longer stay (days) on the ward among patients in the lofexidine arm relative to those in the benzodiazepine arm
- Significantly lower anxiety and depression score on the MAP among patients in the lofexidine arm relative to those in the benzodiazepine arm
Safety Assessment and Monitoring: After signing the informed consent, the subject will undergo screening assessments to determine eligibility for study enrollment; the screen tests include FBC, LFT, Renal function and 12-lead ECG, and urine pregnancy test if female. A complete physical examination will be performed on the first day of screening. From Day 1 till discharge, Vital Signs (e.g. pulse rate, body temperature, blood pressure and respiratory rate) will be closely monitored by the study nurses at the ward, i.e. immediately prior to each lofexidine dose and in addition, 2 hours after the first dose of each dosing day. Should patients show signs of hypotension, the nurse will inform the investigators and they will determine whether or not it is necessary to terminate the patients' participation in the trial. Patients will be required to repeat a 12-lead ECG test when they complete the study or if they drop out of the study. If there is any significant finding from the repeat ECG, it will be followed through by the investigators until resolved. All the adverse events will be documented and followed through until resolved during the study period. The Regular Study Safety Reports inclusive of patients' recruitment, AE/SAE will be generated periodically and sent to an Independent Date \& Safety Monitoring Committee (DSMC) for review, the DSMC comprise addiction medicine experts from outside of IMH. Individual patients or the entire study will be discontinued if there is any major safety finding.
Sample Size and Statistical methods: The estimate of 122 subjects (61 per group) for the sample size is based on the following assumptions - mean (SE) OOWS scores on day 4 of 2.4 (0.4000) and 3.9 (2.7713) for the lofexidine and diazepam groups respectively (which implies an expected absolute treatment effect of 1.5), a power of 80%, and allowing for 30% of the patients dropping out before their evaluation on day 4. Thirty percent dropout implies that 86 subjects (43 per group) are required to evaluate the benefit of lofexidine over diazepam. The primary efficacy analysis will be done using the ITT dataset and the safety profile will be described using the safety dataset. All analysis will be conducted by independent statisticians (SCRI).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lofexidine & Diazepam Placebo | Experimental | Drug: Lofexidine, Drug: Placebo for DiazepamInitial Lofexidine dosage starts from 0.8mg per day, it will be gradually increased by increments of 0.4 to 0.8mg per day up to a maximum of 2.2mg daily. After 3 peak dose days, the dosage will be gradually decreased by 0.2 to 0.6mg per day till to 0.2mg of the last lofexidine dosage in Day 10. The Diazepam placebo will be administrated to the patients with the same frequency, time and number tablets of diazepam in the active comparator arm. |
| Diazepam & Lofexidine Placebo | Active comparator | Drug: Diazepam, Drug: Placebo for LofexidineThe initial dosage of Diazepam is 10 mg per day on Day 1\&2, the dosage will be increased to 15 mg per day on Day 3\&4, subsequently decreased to 10mg per day on Day 5, 5mg per day on Day 6\&7, 2mg per day on Day 8\&9\&10. The Lofexidine placebo will be administrated to the patients with the same frequency, time and number tablets of lofexidine in the experimental arm. |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Patients who meet the DSM-IV criteria for a diagnosis of opiate dependence (as diagnosed by a NAMS psychiatrist).
- Individuals are voluntarily undergoing inpatient opiate withdrawal treatment at the National Addictions Management Service (NAMS).
- Agreeable to participating in the clinical trial and will provide written consent.
- Males or females who are between the ages of 21-55 years. The lower limit of 21 years is in place because of lack of data on younger populations. The upper limit is set at 55 years as the likelihood of having co-morbid physical health problems is greater.
- Individuals who have a positive urine screen for the presence of opiates (routinely given on first visit to outpatient clinic).
Key exclusion criteria (11 listed)
- Are investigator site personnel directly affiliated with this study and their immediate families, immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
- Are currently enrolled in, or discontinued within the last 30 days from another clinical trial or medical research judged not to be scientifically or medically compatible with this study.
- A history of allergy/sensitivity to clonidine, lofexidine, imidazole derivatives (e.g. clotrimazole, antifungal) or alpha-2-adrenergic medications.
- Co-dependency on alcohol, benzodiazepines or any other drug that would require detoxification.
- A history of major physical illness (cardiovascular disease, cerebrovascular disease, renal impairment, liver disease, epilepsy, symptomatic HIV, Hepatitis B and/or C).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LofexidineAlso: BritLofex 0.2mg | Drug | Lofexidine & Diazepam Placebo |
| DiazepamAlso: Apo-Diazepam 5mg and 2mg | Drug | Diazepam & Lofexidine Placebo |
| Placebo for Lofexidine | Drug | Diazepam & Lofexidine Placebo |
| Placebo for Diazepam | Drug | Lofexidine & Diazepam Placebo |
Primary outcome
To evaluate differences in OOWS (Objective Opiate Withdrawal Scale)
Time frame: on day 3 and day 4 during inpatient dotex
5 secondary outcomes
To evaluate differences in SOWS (Short Opiate Withdrawal Scale)
Time frame: on day 3 and day 4 during inpatient detox
To evaluate differences in pupil sizes
Time frame: on days 3 and 4 of inpatient detox
To evaluate differences in craving on the Visual Analogue Scale
Time frame: on days 3 and 4 of inpatient detox
To evaluate differences in time to drop-out (length of stay on the ward)
Time frame: time to drop-out
To evaluate differences in emotional/psychological symptoms
Time frame: every 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2015.
- Derived from this study: PubMed 29910009Guo S, Manning V, Yang Y, Koh PK, Chan E, de Souza NN, Assam PN, Sultana R, Wijesinghe R, Pangjaya J, Kandasami G, Cheok C, Lee KM, Wong KE. Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore. J Subst Abuse Treat. 2018 Aug;91:1-11. doi: 10.1016/j.jsat.2018.04.012. Epub 2018 Apr 25.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Song Guo, Ph.D principal investigator
NAMS IMH Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lofexidine and Diazepam in people with Opiate Dependent Patients Who Are Undergoing Inpatient Detoxification in Singapore, run by Institute of Mental Health, Singapore at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate differences in OOWS (Objective Opiate Withdrawal Scale) (time frame: on day 3 and day 4 during inpatient dotex). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01675648, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2015.