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

April 3, 2015 updated by: US Department of Veterans Affairs

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

368

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: No ARDFP+Standard-ART
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: No ARDFP+Mega-ART
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: ARDFP+Standard-ART
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: ARDFP+Mega-ART
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With 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
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
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
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
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
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With a New, Non-HIV Related Serious Adverse Event
Time Frame: 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
New, on-study non-HIV related Serious Adverse events were compared between Standard-ART (standard) and Mega-ART (intensification)
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
Time Frame: 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
New, on-study non-HIV related Serious Adverse events were compared between ARDFP (interruption) and No ARDFP (continuation)
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Department of Veterans Affairs

Collaborators

Canadian Institutes of Health Research (CIHR)
Medical Research Council

Investigators

  • Study Chair: Sheldon Brown, VA Medical Center, Bronx

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

December 1, 2007

Study Registration Dates

First Submitted

November 20, 2002

First Submitted That Met QC Criteria

November 21, 2002

First Posted (Estimate)

November 22, 2002

Study Record Updates

Last Update Posted (Estimate)

April 23, 2015

Last Update Submitted That Met QC Criteria

April 3, 2015

Last Verified

April 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 512

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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