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 number	NCT00050089
Secondary identifying numbers	JTN-43304; 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

Study website

Contact information

Dr D. William Cameron
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
Email	bcameron@ohri.ca

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Participant information sheet	Patient information can be found at: http://www.optimatrial.org/ca/pdfs/brochure.pdf
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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Anti-retroviral therapy
Primary outcome measure	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.
Secondary outcome measures	1. Time to development of a new non-HIV related serious adverse event 2. Quality of life 3. Incidence of grade 3 or 4 clinical or laboratory adverse events 4. Changes in CD4 counts, viral load and resistance 5. Process measures including hematologic profiles, electrolytes, renal function, liver function and pancreatic function
Overall study start date	01/01/2002
Completion date	01/12/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	504 (as of 07/02/2007: 390)
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

Canada
United Kingdom
United States of America

Study participating centre

The Ottawa Hospital - General Campus

Ontario
K1H 8L6
Canada

Sponsor information

University of British Columbia (Canada)
University/education

2075 Wesbrook Mall
Vancouver
V6T 1Z1
Canada

Website	http://www.ubc.ca/

Medical Research Council (MRC) Clinical Trials Unit (UK)
Research council

222 Euston Road
London
NW1 2DA
United Kingdom

Website	www.ctu.mrc.ac.uk

University of British Columbia
Not defined

Website	https://www.ubc.ca/
"ROR"	https://ror.org/03rmrcq20

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (ref: JTN-43304)
Government organisation / National government

Alternative name(s): Instituts de Recherche en Santé du Canada, Canadian Institutes of Health Research (CIHR), CIHR_IRSC, Canadian Institutes of Health Research | Ottawa ON, CIHR, IRSC
Location: Canada

Medical Research Council (UK) (ref: G9901441)
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Peer reviewed?	Patient-facing?
Basic results			No	No
Protocol article	protocol	01/08/2003	Yes	No
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

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.