Study Results
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View full resultsBasic Information
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COMPLETED
NA
368 participants
INTERVENTIONAL
2001-01-31
2007-12-31
Brief Summary
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Detailed Description
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Compared to patients in Standard Antiretroviral Therapy (ART), patients in Mega-ART assuming full compliance, will experience a 30% reduction in the hazard of reaching a clinical endpoint (AIDS event or death).
Secondary Hypotheses:
Time to development of a new, non-HIV related serious adverse event, health related quality of life, the incidence of grade 3 or 4 clinical or laboratory adverse events and changes in virological and immunological markers (CD4 cell count, viral load, resistance profiles) will vary between the different treatment strategies.
Interventions:
Eligible patients will be randomized to one of four treatment strategy arms:
1. No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART
2. No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART
3. Antiretroviral Drug-Free Period (ARDFP) and Standard-ART
4. Antiretroviral Drug-Free Period (ARDFP) and Mega-ART
Note: The 'first' randomization will be ARDFP vs No ARDFP. Patients randomized to No ARDFP will receive their 'second' randomization at the same time. However, patients randomized to an Antiretroviral Drug Free Period (ARDFP) will receive their 'second' randomized assignment (Standard or Mega-ART) at the end of the ARDFP.
Note: All Serious Adverse Events were coded using the MedDRA coding dictionary; other (not serious) Adverse Events were collected as part of the study but were not coded using MedDRA or any other standardized coding dictionary.
This is the first trial of a Tri-National collaboration effort between the UK MRC, the Canadian CIHR and the VA CSP. The OPTIMA Trial was reviewed and approved by CSEC on October 12, 2000. The pre-kickoff meeting was held on March 21, 2001 in Washington, DC. The VA study kickoff meeting was held in Dallas, TX on May 16-18, 2001 and the Canadian kickoff was held in Toronto on May 29, 2001. The UK will have individual site initiation. As of October 17, 2005 there have been 357 patients enrolled in OPTIMA, at 64 sites in the three countries (279 in the VA, 41 in Canada and 37 in the UK). To date there are 64 sites actively participating in the study (24 in the VA, 19 in UK and 21 in Canada). Last date of patient follow-up was December 31, 2007.
Conditions
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Study Design
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RANDOMIZED
FACTORIAL
TREATMENT
NONE
Study Groups
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No ARDFP+Standard-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
No ARDFP+Mega-ART
No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
ARDFP+Standard-ART
Antiretroviral Drug-Free Period (ARDFP) and Standard-ART
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
ARDFP+Mega-ART
Antiretroviral Drug-Free Period (ARDFP) and Mega-ART
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
Interventions
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No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Standard ART vs Mega ART
Standard therapy vs Intensified therapy
Eligibility Criteria
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Inclusion Criteria
* Age of 18 years or more
* Serologic or virologic diagnosis of HIV infection
* Failure of at least two different multi-drug regimens that include drugs of all 3 classes that the patient can tolerate or laboratory evidence of resistance to drugs in each of the 3 classes
* Had at least 3 months of current ART and are still on treatment
* Two most recent results (which can include screening) on current ART of CD4 count less than or equal to 300 cells/mm3 or less than or equal to 15%, and a plasma viral load greater than or equal to 5,000 copies/ml (Roche Amplicor, v1.0), or greater than or equal to 2,500 copies/ml (by bDNA: Bayer v3.0/Chiron v3.0 or PCR:Roche Amplicor Monitor/COBAS v1.5)
Exclusion Criteria
* Likelihood of poor protocol follow-up or if Mega-Art is not feasible (due to significant intolerance of many ARV drugs)
* Serious, uncontrolled major opportunistic infection (OI) within 14 days of screening
* Likelihood of early death due to non-HIV disease
18 Years
ALL
No
Sponsors
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Medical Research Council
OTHER_GOV
Canadian Institutes of Health Research (CIHR)
OTHER_GOV
US Department of Veterans Affairs
FED
Responsible Party
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Principal Investigators
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Sheldon Brown
Role: STUDY_CHAIR
VA Medical Center, Bronx
Locations
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Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States
VA Medical Center, Long Beach
Long Beach, California, United States
VA Palo Alto Health Care System
Palo Alto, California, United States
VA San Diego Healthcare System, San Diego
San Diego, California, United States
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, United States
VA Medical Center, DC
Washington D.C., District of Columbia, United States
North Florida/South Georgia Veterans Health System
Gainesville, Florida, United States
VA Medical Center, Miami
Miami, Florida, United States
Bay Pines VAMC (111J)
St. Petersburg, Florida, United States
West Palm Beach VA Medical Center
West Palm Beach, Florida, United States
Atlanta VA Medical and Rehab Center, Decatur
Decatur, Georgia, United States
Jesse Brown VAMC (WestSide Division)
Chicago, Illinois, United States
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States
VA Maryland Health Care System, Baltimore
Baltimore, Maryland, United States
VA Medical Center, Jamaica Plain Campus
Boston, Massachusetts, United States
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States
VA New Jersey Health Care System, East Orange
East Orange, New Jersey, United States
New York Harbor HCS
New York, New York, United States
VA Medical Center, Bronx
The Bronx, New York, United States
VA Medical Center, Durham
Durham, North Carolina, United States
VA Medical Center, Cincinnati
Cincinnati, Ohio, United States
VA Medical Center, Cleveland
Cleveland, Ohio, United States
VA Medical Center, Portland
Portland, Oregon, United States
VA Medical Center, Philadelphia
Philadelphia, Pennsylvania, United States
WJB Dorn Veterans Hospital, Columbia
Columbia, South Carolina, United States
VA North Texas Health Care System, Dallas
Dallas, Texas, United States
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, United States
VA South Texas Health Care System, San Antonio
San Antonio, Texas, United States
VA Medical Center, San Juan
San Juan, , Puerto Rico
Countries
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References
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Kyriakides TC, Babiker A, Singer J, Cameron W, Schechter MT, Holodniy M, Brown ST, Youle M, Gazzard B; OPTIMA Study Team. 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 Aug;24(4):481-500. doi: 10.1016/s0197-2456(03)00029-1.
Bedimo R, Kyriakides T, Brown S, Weidler J, Lie Y, Coakley E, Holodniy M. Predictive value of HIV-1 replication capacity and phenotypic susceptibility scores in antiretroviral treatment-experienced patients. HIV Med. 2012 Jul;13(6):345-51. doi: 10.1111/j.1468-1293.2011.00981.x. Epub 2012 Jan 26.
Kyriakides TC, Babiker A, Singer J, Piaseczny M, Russo J. Study conduct, monitoring and data management in a trinational trial: the OPTIMA model. Clin Trials. 2004;1(3):277-81. doi: 10.1191/1740774504cn022oa.
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 Jun;54(2):160-6. doi: 10.1097/QAI.0b013e3181cbd235.
Bansback N, Sun H, Guh DP, Li X, Nosyk B, Griffin S, Barnett PG, Anis AH; OPTIMA TEAM. Impact of the recall period on measuring health utilities for acute events. Health Econ. 2008 Dec;17(12):1413-9. doi: 10.1002/hec.1351.
Desai S, Kyriakides T, Holodniy M, Al-Salman J, Griffith B, Kozal M. Evolution of genotypic resistance algorithms and their impact on the interpretation of clinical trials: an OPTIMA trial substudy. HIV Clin Trials. 2007 Sep-Oct;8(5):293-302. doi: 10.1310/hct0805-293.
Barnett PG, Chow A, Joyce VR, Bayoumi AM, Griffin SC, Nosyk B, Holodniy M, Brown ST, Sculpher M, Anis AH, Owens DK. Determinants of the cost of health services used by veterans with HIV. Med Care. 2011 Sep;49(9):848-56. doi: 10.1097/MLR.0b013e31821b34c0.
Nosyk B, Sun H, Bansback N, Guh DP, Li X, Barnett P, Bayoumi A, Griffin S, Joyce V, Holodniy M, Owens DK, Anis AH. The concurrent validity and responsiveness of the health utilities index (HUI 3) among patients with advanced HIV/AIDS. Qual Life Res. 2009 Sep;18(7):815-24. doi: 10.1007/s11136-009-9504-0. Epub 2009 Jun 27.
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; OPTIMA Team1. 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 Aug 15;51(5):631-9. doi: 10.1097/QAI.0b013e3181a4f00d.
Joyce VR, Barnett PG, Bayoumi AM, Griffin SC, Kyriakides TC, Yu W, Sundaram V, Holodniy M, Brown ST, Cameron W, Youle M, Sculpher M, Anis AH, Owens DK. Health-related quality of life in a randomized trial of antiretroviral therapy for advanced HIV disease. J Acquir Immune Defic Syndr. 2009 Jan 1;50(1):27-36. doi: 10.1097/QAI.0b013e31818ce6f3.
Joyce VR, Barnett PG, Chow A, Bayoumi AM, Griffin SC, Sun H, Holodniy M, Brown ST, Kyriakides TC, Cameron DW, Youle M, Sculpher M, Anis AH, Owens DK. Effect of treatment interruption and intensification of antiretroviral therapy on health-related quality of life in patients with advanced HIV: a randomized, controlled trial. Med Decis Making. 2012 Jan-Feb;32(1):70-82. doi: 10.1177/0272989X10397615. Epub 2011 Mar 7.
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; OPTIMA Team. Results of antiretroviral treatment interruption and intensification in advanced multi-drug resistant HIV infection from the OPTIMA trial. PLoS One. 2011 Mar 31;6(3):e14764. doi: 10.1371/journal.pone.0014764.
Other Identifiers
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512
Identifier Type: -
Identifier Source: org_study_id
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