CSP #512 - Options in Management With Anti-Retrovirals

NCT00050089 | Completed Results

• 1 other identifier: 512
• Study Type: interventional
• Target: 368
• Locations: 2 countries
• Sites: 30

Brief Summary

This 'pragmatic' trial is a 2X2 open randomized study of patients in advanced HIV disease who have failed on conventional Highly Active Antiretroviral Therapy (HAART) regimens including all three classes of anti-HIV drugs. The first randomization will allocate patients to an intended 3-month antiretroviral drug-free period (ARDFP) or No ARDFP. The second randomization will allocate patients to Mega-ART (5+ drugs) or to Standard-ART (up to 4 drugs). The total study duration is 6.5 years with 5 years of intake and 1.5 year (minimum) of follow-up; median duration of patient follow-up is about 4 years. The target sample size is 390 patients and will provide 75% power to detect a 30% reduction in the hazard rate for the primary endpoint with mega-ART. Sixty-four sites will be participating in the trial--24 VA, 19 UK and 21 Canada.

Conditions

AIDS; HIV Infections

Keywords

AIDS; antiretrovirals; ART; drug-free period; HAART; HIV; human immunodeficiency virus; randomized; structured treatment interruptions

Outcome Measures

Primary Outcomes (3)

• Number of Participants With New or Recurrent AIDS Event, or Death

  New or recurrent AIDS event or Death were compared between Standard-ART (standard) and Mega-ART (intensification)

  From date of randomization until onset of primary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years

• Number of Participants With New or Recurrent AIDS Event, or Death

  New or recurrent AIDS event or Death were compared between No ARDFP (continuation) and ARDFP (interruption)

  From date of randomization until onset of primary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years

• Number of Participants With New or Recurrent AIDS Event, or Death

  New or recurrent AIDS event or Death were compared between No ARDFP (continuation)+Standard-ART (standard), No ARDFP (continuation)+Mega-ART (intensification), ARDFP (interruption)+Standard-ART (standard) and ARDFP (interruption)+Mega-ART (intensification)

  From date of randomization until onset of primary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years

Secondary Outcomes (2)

• Number of Participants With a New, Non-HIV Related Serious Adverse Event

  From date of randomization until onset of secondary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years

• Number of Participants With New, Non-HIV Related Serious Adverse Event

  From date of randomization until onset of secondary outcome or end of study follow-up (12/31/2007) whichever occured first, up to 6.5 years

Study Arms (4)

No ARDFP+Standard-ART

ACTIVE COMPARATOR

No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART

Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP; Drug: Standard ART vs Mega ART

No ARDFP+Mega-ART

ACTIVE COMPARATOR

No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART

Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP; Drug: Standard ART vs Mega ART

ARDFP+Standard-ART

ACTIVE COMPARATOR

Antiretroviral Drug-Free Period (ARDFP) and Standard-ART

Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP; Drug: Standard ART vs Mega ART

ARDFP+Mega-ART

ACTIVE COMPARATOR

Antiretroviral Drug-Free Period (ARDFP) and Mega-ART

Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP; Drug: Standard ART vs Mega ART

Interventions

No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP OTHER

Continuation or interruption of ART treatment

No ARDFP+Standard-ART

Standard ART vs Mega ART DRUG

Standard therapy vs Intensified therapy

No ARDFP+Standard-ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• 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)

You may not qualify if:

• Pregnancy, breast-feeding or planned pregnancy
• 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

Sponsors & Collaborators

• US Department of Veterans Affairs: lead
• Medical Research Council: collaborator
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (30)

Carl T. Hayden VA Medical Center

Phoenix, Arizona, 85012, United States

Location

VA Medical Center, Long Beach

Long Beach, California, 90822, United States

Location

VA Palo Alto Health Care System

Palo Alto, California, 94304-1290, United States

Location

VA San Diego Healthcare System, San Diego

San Diego, California, 92161, United States

Location

VA Greater Los Angeles Healthcare System, West LA

West Los Angeles, California, 90073, United States

Location

VA Connecticut Health Care System (West Haven)

West Haven, Connecticut, 06516, United States

Location

VA Medical Center, DC

Washington D.C., District of Columbia, 20422, United States

Location

North Florida/South Georgia Veterans Health System

Gainesville, Florida, 32608, United States

Location

VA Medical Center, Miami

Miami, Florida, 33125, United States

Location

Bay Pines VAMC (111J)

St. Petersburg, Florida, 33708, United States

Location

West Palm Beach VA Medical Center

West Palm Beach, Florida, 33410, United States

Location

Atlanta VA Medical and Rehab Center, Decatur

Decatur, Georgia, 30033, United States

Location

Jesse Brown VAMC (WestSide Division)

Chicago, Illinois, 60612, United States

Location

Edward Hines, Jr. VA Hospital

Hines, Illinois, 60141-5000, United States

Location

VA Maryland Health Care System, Baltimore

Baltimore, Maryland, 21201, United States

Location

VA Medical Center, Jamaica Plain Campus

Boston, Massachusetts, 02130, United States

Location

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48113, United States

Location

VA New Jersey Health Care System, East Orange

East Orange, New Jersey, 07018, United States

Location

New York Harbor HCS

New York, New York, 10010, United States

Location

VA Medical Center, Bronx

The Bronx, New York, 10468, United States

Location

VA Medical Center, Durham

Durham, North Carolina, 27705, United States

Location

VA Medical Center, Cincinnati

Cincinnati, Ohio, 45220, United States

Location

VA Medical Center, Cleveland

Cleveland, Ohio, 44106, United States

Location

VA Medical Center, Portland

Portland, Oregon, 97201, United States

Location

VA Medical Center, Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

WJB Dorn Veterans Hospital, Columbia

Columbia, South Carolina, 29209, United States

Location

VA North Texas Health Care System, Dallas

Dallas, Texas, 75216, United States

Location

Michael E. DeBakey VA Medical Center (152)

Houston, Texas, 77030, United States

Location

VA South Texas Health Care System, San Antonio

San Antonio, Texas, 78229, United States

Location

VA Medical Center, San Juan

San Juan, 00921, Puerto Rico

Location

Related Publications (12)

• 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.

  PMID: 12865041 BACKGROUND

• 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.

  PMID: 22276745 BACKGROUND

• 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.

  PMID: 16279253 BACKGROUND

• 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.

  PMID: 20130473 BACKGROUND

• 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.

  PMID: 18404664 BACKGROUND

• 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.

  PMID: 17956830 BACKGROUND

• 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.

  PMID: 21610542 RESULT

• 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.

  PMID: 19562514 RESULT

• 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.

  PMID: 19430303 RESULT

• 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.

  PMID: 19295332 RESULT

• 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.

  PMID: 21383086 RESULT

• 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.

  PMID: 21483491 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Dr. Sheldon Brown
• Organization: VAMC Bronx

sheldon.brown@va.gov

(718) 584-9000

Study Officials

• Sheldon Brown

  VA Medical Center, Bronx

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2002
• First Posted: November 22, 2002
• Study Start: January 1, 2001
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: April 23, 2015
• Results First Posted: February 13, 2014

Record last verified: 2015-04

Locations

US (29); PR (1)