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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

  Show 30 Study Locations
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
Communicable Diseases
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014