TNT-1:OPTIMA (Tri-National Trial 1: Options in Management with Anti-retrovirals) - A tri-national (Canada, UK, USA) randomised controlled trial to determine the optimal management of patients with Human Immunodeficiency Virus (HIV) infection for whom first and second-line Highly Active Anti-Retroviral Therapy (HAART) has failed
| ISRCTN | ISRCTN19619965 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN19619965 |
| ClinicalTrials.gov (NCT) | NCT00050089 |
| Protocol serial number | JTN-43304; G9901441 |
| Sponsors | University of British Columbia (Canada), Medical Research Council (MRC) Clinical Trials Unit (UK) , University of British Columbia |
| Funders | Canadian Institutes of Health Research (ref: JTN-43304), Medical Research Council (UK) (ref: G9901441) |
- Submission date
- 19/01/2001
- Registration date
- 19/01/2001
- Last edited
- 21/03/2016
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr D. William Cameron
Scientific
Scientific
The Ottawa Hospital - General Campus
501 Smyth Road
Clinical Epidemiology Program, Rm. 1818
Box 228
Ottawa
Ontario
K1H 8L6
Canada
| Phone | +1 (0)613 737 8880 |
|---|---|
| bcameron@ohri.ca |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | TNT-1:OPTIMA (Tri-National Trial 1: Options in Management with Anti-retrovirals) - A tri-national (Canada, UK, USA) randomised controlled trial to determine the optimal management of patients with Human Immunodeficiency Virus (HIV) infection for whom first and second-line Highly Active Anti-Retroviral Therapy (HAART) has failed |
| Study acronym | OPTIMA |
| Study objectives | The OPTIMA trial is a large-scale, multicentre, randomised controlled trial to compare the relative efficacy of two different therapeutic strategies: 1. A drug free period 2. Increasing the number of HIV drugs in treating HIV infection after the most effective drug combinations have failed. |
| Ethics approval(s) | Ottawa Hospital Research Ethics Board, 20/11/2001 |
| Health condition(s) or problem(s) studied | HIV, Acquired Immune Deficiency Syndrome (AIDS) |
| Intervention | 1. Start a standard-ART regimen (up to four HIV drugs) 2. Start a mega-ART regimen (five or more HIV drugs) 3. Interrupt ART for 12 weeks then start a standard-ART regimen (up to four HIV drugs) 4. Interrupt ART for 12 weeks then start a mega-ART regimen (five or more HIV drugs) Added as of 07/02/2007 for UK part of trial: You can now join this study in the UK in one of three ways: Option 1: As in the main OPTIMA study, you will be randomised (similar to tossing a coin or rolling a dice) to both parts of the study. You will have a drug-free period of three months, or no drug-free period and then receive either 'standard ART' or 'mega-ART treatment. Option 2: You can choose whether or not to have a drug free period, and then be randomised for how many drugs you will take. Option 3: You can choose how many drugs you will take, and then be randomised to whether you will have a drug free period or not. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Anti-retroviral therapy |
| Primary outcome measure(s) |
The time to new or recurrent AIDS-defining event or death and time to a new non-HIV related serious adverse event are main clinical outcomes. |
| Key secondary outcome measure(s) |
1. Time to development of a new non-HIV related serious adverse event |
| Completion date | 01/12/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 504 |
| Key inclusion criteria | 1. Signed informed consent 2. Age 18 years or more, either sex 3. HIV-1 infection confirmed by Enzyme-Linked Immuno-Sorbent Assay (ELISA) or Western Blot or detectable HIV viral load at any time 4. Failure of at least two different multi-drug regimens, which included drugs of all classes that the patient can tolerate 5. At least 3 months continuous HAART and still on treatment 6. Two most recent results (can include screening) on current Anti-Retroviral Therapy (ART) of either: 6.1. CD4 less than 100 plus plasma Viral Load (pVL) greater than 5000 copies, or 6.2. CD4 100 - 199 plus pVL greater than 10,000 copies *If VL testing available defined as either: failure to suppress pVL after 24 weeks of therapy, or rebound of at least 0.5 log10 in pVL from the nadir. In the era before pVL available defined as: a decline in the CD4 count over 50% from the peak, or progression of HIV disease. |
| Key exclusion criteria | 1. Pregnancy, breast-feeding or planned pregnancy 2. Likelihood of poor protocol follow-up or if Mega-ART is not feasible (due to significant intolerance of many ART drugs) 3. Serious, uncontrolled major opportunistic infection (OI) within 14 days of screening 4. Likelihood of early death due to non HIV-disease 5. Any medical condition or current medication, in the opinion of the treating physician, which would contraindicate anti-HIV treatment as allocated in the trial Exclusion criteria for UK arm of trial added as of 07/02/2007: 1. Pregnancy, breast-feeding or planned pregnancy 2. Likelihood of poor protocol follow-up or if Mega-ART is not feasible* (due to significant intolerance of many ARV rugs) 3. Serious, uncontrolled major opportunistic infection (OI) within 14 days of screening 4. Likelihood of early death due to non-HIV disease *Patients exempt from second part of this question if entering option 3 |
| Date of first enrolment | 01/01/2002 |
| Date of final enrolment | 01/12/2007 |
Locations
Countries of recruitment
- United Kingdom
- Canada
- United States of America
Study participating centre
The Ottawa Hospital - General Campus
Ontario
K1H 8L6
Canada
K1H 8L6
Canada
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | quality of life results | 15/08/2009 | Yes | No | |
| Results article | mutation frequency results | 01/06/2010 | Yes | No | |
| Results article | results | 31/03/2011 | Yes | No | |
| Protocol article | protocol | 01/08/2003 | Yes | No | |
| Basic results | No | No | |||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
21/03/2016: added link to results - basic reporting.
Please note that the overall trial end date provided at time of registration was 31/01/2007.
