CSP #512 - Options in Management With Anti-Retrovirals (OPTIMA)

This study has been completed.
Sponsor:
Collaborators:
Medical Research Council
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00050089
First received: November 20, 2002
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

This 'pragmatic' trial is a 2X2 open randomized study of patients in advanced HIV disease who have failed on conventional HAART (Highly Active Antiretroviral Therapy) 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.


Condition Intervention
AIDS
HIV Infections
Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Drug: Standard ART vs Mega ART

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: CSP #512 - Options in Management With Anti-Retrovirals (OPTIMA), Management of Patients With HIV Infection for Whom First and Second-line Highly Active Anti-Retroviral Therapy Has Failed

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Participants Who Developed a New or Recurrent AIDS Event or Death [ Time Frame: 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 ] [ Designated as safety issue: No ]

Enrollment: 368
Study Start Date: January 2001
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1
No Antiretroviral Drug-Free Period (No ARDFP) and Standard-ART
Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Drug: Standard ART vs Mega ART
Standard therapy vs Intensified therapy
Active Comparator: Arm 2
No Antiretroviral Drug-Free Period (No ARDFP) and Mega-ART
Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Drug: Standard ART vs Mega ART
Standard therapy vs Intensified therapy
Active Comparator: Arm 3
Antiretroviral Drug-Free Period (ARDFP) and Standard-ART
Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Drug: Standard ART vs Mega ART
Standard therapy vs Intensified therapy
Active Comparator: Arm 4
Antiretroviral Drug-Free Period (ARDFP) and Mega-ART
Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Continuation or interruption of ART treatment
Drug: Standard ART vs Mega ART
Standard therapy vs Intensified therapy

Detailed Description:

Primary Hypothesis:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00050089

  Hide Study Locations
Locations
United States, Arizona
Carl T. Hayden VA Medical Center
Phoenix, Arizona, United States, 85012
United States, California
VA Medical Center, Long Beach
Long Beach, California, United States, 90822
VA Palo Alto Health Care System
Palo Alto, California, United States, 94304-1290
VA San Diego Healthcare System, San Diego
San Diego, California, United States, 92161
VA Greater Los Angeles Healthcare System, West LA
West Los Angeles, California, United States, 90073
United States, Connecticut
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, United States, 06516
United States, District of Columbia
VA Medical Center, DC
Washington, District of Columbia, United States, 20422
United States, Florida
North Florida/South Georgia Veterans Health System
Gainesville, Florida, United States, 32608
VA Medical Center, Miami
Miami, Florida, United States, 33125
Bay Pines VAMC (111J)
St. Petersburg, Florida, United States, 33708
West Palm Beach VA Medical Center
West Palm Beach, Florida, United States, 33410
United States, Georgia
Atlanta VA Medical and Rehab Center, Decatur
Decatur, Georgia, United States, 30033
United States, Illinois
Jesse Brown VAMC (WestSide Division)
Chicago, Illinois, United States, 60612
Edward Hines, Jr. VA Hospital
Hines, Illinois, United States, 60141-5000
United States, Maryland
VA Maryland Health Care System, Baltimore
Baltimore, Maryland, United States, 21201
United States, Massachusetts
VA Medical Center, Jamaica Plain Campus
Boston, Massachusetts, United States, 02130
United States, Michigan
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, United States, 48113
United States, New Jersey
VA New Jersey Health Care System, East Orange
East Orange, New Jersey, United States, 07018
United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468
New York Harbor HCS
New York, New York, United States, 10010
United States, North Carolina
VA Medical Center, Durham
Durham, North Carolina, United States, 27705
United States, Ohio
VA Medical Center, Cincinnati
Cincinnati, Ohio, United States, 45220
VA Medical Center, Cleveland
Cleveland, Ohio, United States, 44106
United States, Oregon
VA Medical Center, Portland
Portland, Oregon, United States, 97201
United States, Pennsylvania
VA Medical Center, Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, South Carolina
WJB Dorn Veterans Hospital, Columbia
Columbia, South Carolina, United States, 29209
United States, Texas
VA North Texas Health Care System, Dallas
Dallas, Texas, United States, 75216
Michael E. DeBakey VA Medical Center (152)
Houston, Texas, United States, 77030
VA South Texas Health Care System, San Antonio
San Antonio, Texas, United States, 78229
Puerto Rico
VA Medical Center, San Juan
San Juan, Puerto Rico, 00921
Sponsors and Collaborators
Medical Research Council
Canadian Institutes of Health Research (CIHR)
Investigators
Study Chair: Sheldon Brown VA Medical Center, Bronx
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00050089     History of Changes
Other Study ID Numbers: 512
Study First Received: November 20, 2002
Results First Received: September 11, 2013
Last Updated: January 17, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
AIDS
antiretrovirals
ART
drug-free period
HAART
HIV
human immunodeficiency virus
randomized
structured treatment interruptions

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014