Condition category
Infections and Infestations
Date applied
19/01/2001
Date assigned
19/01/2001
Last edited
21/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.optimatrial.org/ca/

Contact information

Type

Scientific

Primary contact

Dr D. William Cameron

ORCID ID

Contact details

The Ottawa Hospital - General Campus
501 Smyth Road
Clinical Epidemiology Program
Rm. 1818
Box 228
Ottawa
Ontario
K1H 8L6
Canada
+1 (0)613 737 8880
bcameron@ohri.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT00050089

Protocol/serial number

JTN-43304; G9901441

Study information

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

Acronym

OPTIMA

Study hypothesis

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

Ottawa Hospital Research Ethics Board, 20/11/2001

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Treatment

Patient information sheet

Patient information can be found at: http://www.optimatrial.org/ca/pdfs/brochure.pdf

Condition

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 names

Anti-retroviral therapy

Primary outcome measures

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 trial start date

01/01/2002

Overall trial end date

01/12/2007

Reason abandoned

Eligibility

Participant 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.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

504 (as of 07/02/2007: 390)

Participant 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

Recruitment start date

01/01/2002

Recruitment end date

01/12/2007

Locations

Countries of recruitment

Canada, United Kingdom, United States of America

Trial participating centre

The Ottawa Hospital - General Campus
Ontario
K1H 8L6
Canada

Sponsor information

Organisation

University of British Columbia (Canada)

Sponsor details

2075 Wesbrook Mall
Vancouver
V6T 1Z1
Canada

Sponsor type

University/education

Website

http://www.ubc.ca/

Organisation

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

Sponsor details

222 Euston Road
London
NW1 2DA
United Kingdom

Sponsor type

Research council

Website

www.ctu.mrc.ac.uk

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (ref: JTN-43304)

Alternative name(s)

Instituts de Recherche en Santé du Canada, CIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

Canada

Funder name

Medical Research Council (UK) (ref: G9901441)

Alternative name(s)

MRC

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

See https://clinicaltrials.gov/ct2/show/results/NCT00050089

Publication summary

2003 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/12865041
2007 quality of life results in: http://www.ncbi.nlm.nih.gov/pubmed/19430303
2010 mutation frequency results in: http://www.ncbi.nlm.nih.gov/pubmed/20130473
2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21483491

Publication citations

  1. Protocol

    Kyriakides TC, Babiker A, Singer J, Cameron W, Schechter MT, Holodniy M, Brown ST, Youle M, Gazzard B, , An open-label randomized clinical trial of novel therapeutic strategies for HIV-infected patients in whom antiretroviral therapy has failed: rationale and design of the OPTIMA Trial., Control Clin Trials, 2003, 24, 4, 481-500.

  2. Quality of life results

    Anis AH, Nosyk B, Sun H, Guh DP, Bansback N, Li X, Barnett PG, Joyce V, Swanson KM, Kyriakides TC, Holodniy M, Cameron DW, Brown ST, , Quality of life of patients with advanced HIV/AIDS: measuring the impact of both AIDS-defining events and non-AIDS serious adverse events., J. Acquir. Immune Defic. Syndr., 2009, 51, 5, 631-639, doi: 10.1097/QAI.0b013e3181a4f00d.

  3. Mutation frequency results

    Dau B, Ayers D, Singer J, Harrigan PR, Brown S, Kyriakides T, Cameron DW, Angus B, Holodniy M, Connection domain mutations in treatment-experienced patients in the OPTIMA trial., J. Acquir. Immune Defic. Syndr., 2010, 54, 2, 160-166, doi: 10.1097/QAI.0b013e3181cbd235.

  4. Results

    Holodniy M, Brown ST, Cameron DW, Kyriakides TC, Angus B, Babiker A, Singer J, Owens DK, Anis A, Goodall R, Hudson F, Piaseczny M, Russo J, Schechter M, Deyton L, Darbyshire J, , Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial., PLoS ONE, 2011, 6, 3, e14764, doi: 10.1371/journal.pone.0014764.

Additional files

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.