Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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):
VA Office of Research and Development
ClinicalTrials.gov Identifier:
NCT00050089
First received: November 20, 2002
Last updated: April 3, 2015
Last verified: April 2015
Results First Received: September 11, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: AIDS
HIV Infections
Interventions: Other: No Antiretroviral Drug-Free Period (No ARDFP) vs ARDFP
Drug: Standard ART vs Mega ART

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 368 participants were enrolled in the trial: 41 in Canada, 39 in the UK and 288 in the US-VA.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
339 participants were randomized to factorial design(Canada=41;UK=10;US-VA=288). 29 participants in the UK were enrolled in a protocol-approved option, where they were allowed to select one of the factors and be randomized to the other. All 29 selected the ARDFP vs No ARDFP factor and were randomized to the Standard-ART vs Mega-ART factor.

Reporting Groups
  Description
No ARDFP+Standard-ART

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

Standard-ART: up to 4 anti-HIV drugs

No ARDFP+Mega-ART

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

Mega-ART: 5 or more anti-HIV drugs

ARDFP+Standard-ART

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

Intended duration of ARDFP: 12 week2 Standard-ART: up to 4 anti-HIV drugs

ARDFP+Mega-ART

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

Intended duration of ARDFP: 12 weeks Mega-ART: 5 or more anti-HIV drugs


Participant Flow:   Overall Study
    No ARDFP+Standard-ART   No ARDFP+Mega-ART   ARDFP+Standard-ART   ARDFP+Mega-ART
STARTED   106   98   86   78 
Baseline   91 [1]   84 [2]   86   78 
COMPLETED   106 [3]   98 [3]   86 [3]   78 [3] 
NOT COMPLETED   0   0   0   0 
[1] 15 participants randomized in the UK Option scheme (not displayed in the 2X2 baseline data)
[2] 14 participants randomized in the UK Option scheme (not shown in 2X2 baseline data)
[3] For primary outcome assessment



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
HIV-positive patients with a CD4 count <=300 cells/ul who had prior anti-retroviral treatment failure requiring retreatment

Reporting Groups
  Description
No ARDFP + Standard ART Standard Antiretroviral Treatment regimen
No ARDFP + Mega ART Intensive Antiretroviral Treatment regimen
ARDFP + Standard ART Antiretroviral Treatment Interruption and Standard ART
ARDFP + Mega ART Antiretroviral Treatment Interruption and Intensive ART
Total Total of all reporting groups

Baseline Measures
   No ARDFP + Standard ART   No ARDFP + Mega ART   ARDFP + Standard ART   ARDFP + Mega ART   Total 
Overall Participants Analyzed 
[Units: Participants]
 91   84   86   78   339 
Age 
[Units: Years]
Mean (Standard Deviation)
 48.7  (8.99)   48.3  (7.92)   49.2  (8.1)   48.2  (8.58)   48.6  (8.39) 
Age, Customized 
[Units: Participants]
         
31-40 years   16   11   12   15   54 
41-50 years   35   41   36   30   142 
51-60 years   33   28   31   28   120 
>60 years   7   4   7   5   23 
Gender 
[Units: Participants]
         
Female   1   2   2   2   7 
Male   90   82   84   76   332 
Race/Ethnicity, Customized 
[Units: Participants]
         
White   42   45   38   35   160 
Black   41   30   36   31   138 
Asian   1   0   0   0   1 
Hispanic   6   9   9   12   36 
Aboriginal   1   0   1   0   2 
Other   0   0   2   0   2 
Region of Enrollment 
[Units: Participants]
         
United States   77   71   73   67   288 
United Kingdom   2   2   3   3   10 
Canada   12   11   10   8   41 
log10 Viral Load 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.76  (0.55)   4.75  (0.76)   4.64  (0.67)   4.7  (0.75)   4.71  (0.68) 
CD4 cells/mm3 
[Units: Cells/mm^3]
Mean (Standard Deviation)
 136  (112)   127  (107)   130  (106)   127  (106)   130  (108) 
CD4 level 
[Units: Participants]
         
CD4 <=100 cells/mm^3   38   38   36   33   145 
CD4 >100 cells/mm^3   53   46   50   45   194 
Mode of HIV Infection 
[Units: Participants]
         
Blood   12   7   8   7   34 
Heterosexual   20   19   22   19   80 
Intravenous Drug Use (IVDU)   11   16   15   9   51 
Men who have Sex with Men (MSM)   42   37   37   39   155 
Other   6   5   2   4   17 
Unknown   0   0   2   0   2 
AIDS at entry [1] 
[Units: Participants]
         
Yes   59   46   44   51   200 
No   32   38   42   27   139 
[1] History of AIDS event at study entry
Hepatitis B (HBsAg) 
[Units: Participants]
         
Yes   10   4   15   8   37 
No   81   80   71   70   302 
Hepatitis C (Hep C anti-HCV) 
[Units: Participants]
         
Yes   17   21   27   12   77 
No   74   63   59   66   262 
OI medications for prophylaxis [1] 
[Units: Participants]
         
Anti-PCP   75   67   71   62   275 
Anti-CMV   2   0   2   0   4 
Antibacterial   43   39   33   37   152 
Antifungal   22   23   22   19   86 
[1] Opportunistic Infections medications for prophylaxis at study entry
Concomitant Medications [1] 
[Units: Participants]
         
Lipid Lowering   24   20   33   21   98 
Other antiviral   43   30   30   33   136 
[1] Not all study participants were on other Concomitant Medications. Numbers provided represent participants on those medications at baseline.


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   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 ]

Measure Type Primary
Measure Title Number of Participants With New or Recurrent AIDS Event, or Death
Measure Description New or recurrent AIDS event or Death were compared between Standard-ART (standard) and Mega-ART (intensification)
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This includes participants randomized to Standard-ART or Mega-ART (339 via the 2X2 factorial design and 29 via the UK Option Scheme)

Reporting Groups
  Description
Standard-ART This includes participants randomized to Standard-ART (No ARDFP+Standard-ART or ARDFP+Standard-ART)
Mega-ART This includes participants randomized to Mega-ART (No ARDFP+Mega-ART or ARDFP+Mega-ART)

Measured Values
   Standard-ART   Mega-ART 
Participants Analyzed 
[Units: Participants]
 192   176 
Number of Participants With New or Recurrent AIDS Event, or Death 
[Units: Participants]
 83   82 


Statistical Analysis 1 for Number of Participants With New or Recurrent AIDS Event, or Death
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.69
Hazard Ratio (HR) [4] 1.165
95% Confidence Interval 0.856 to 1.585
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Time-to-event (Kaplan-Meier) and stratified log-rank test was used for the comparison.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  The comparison was Mega-ART (intensification) vs Standard-ART (standard).



2.  Primary:   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 ]

Measure Type Primary
Measure Title Number of Participants With New or Recurrent AIDS Event, or Death
Measure Description New or recurrent AIDS event or Death were compared between No ARDFP (continuation) and ARDFP (interruption)
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This includes participants randomized to No ARDFP or ARDFP (339 via the 2X2 factorial design and 0 via the UK Option Scheme)

Reporting Groups
  Description
ARDFP This includes participants randomized to ARDFP (ARDFP+Standard-ART or ARDFP+Mega-ART)
No ARDFP This includes participants randomized to No ARDFP (No ARDFP+Standard-ART or No ARDFP+Mega-ART)

Measured Values
   ARDFP   No ARDFP 
Participants Analyzed 
[Units: Participants]
 164   175 
Number of Participants With New or Recurrent AIDS Event, or Death 
[Units: Participants]
 70   87 


Statistical Analysis 1 for Number of Participants With New or Recurrent AIDS Event, or Death
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.49
Hazard Ratio (HR) [4] 0.927
95% Confidence Interval 0.674 to 1.275
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Time-to-event (Kaplan-Meier) and stratified log-rank analysis was performed.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  The comparison was ARDFP (interruption) vs No ARDFP (continuation)



3.  Primary:   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 ]

Measure Type Primary
Measure Title Number of Participants With New or Recurrent AIDS Event, or Death
Measure Description 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)
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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
This includes participants randomized to one of the four interventions (339 via the 2X2 factorial design)

Reporting Groups
  Description
No ARDFP + Standard ART Standard ART regimen, with no prior ART interruption
No ARDFP + Mega ART Intensive ART regimen, with no prior ART interruption
ARDFP + Standard ART Standard ART regimen following ART interruption
ARDFP + Mega ART Intensive ART following ART interruption

Measured Values
   No ARDFP + Standard ART   No ARDFP + Mega ART   ARDFP + Standard ART   ARDFP + Mega ART 
Participants Analyzed 
[Units: Participants]
 91   84   86   78 
Number of Participants With New or Recurrent AIDS Event, or Death 
[Units: Participants]
 46   41   35   35 


Statistical Analysis 1 for Number of Participants With New or Recurrent AIDS Event, or Death
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.87
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Stratified Log-rank test was used to compare the four treatment
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



4.  Secondary:   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 ]

Measure Type Secondary
Measure Title Number of Participants With a New, Non-HIV Related Serious Adverse Event
Measure Description New, on-study non-HIV related Serious Adverse events were compared between Standard-ART (standard) and Mega-ART (intensification)
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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Standard-ART This includes participants randomized to Standard-ART (No ARDFP+Standard-ART or ARDFP+Standard-ART)
Mega-ART This includes participants randomized to Mega-ART (No ARDFP+Mega-ART or ARDFP+Mega-ART)

Measured Values
   Standard-ART   Mega-ART 
Participants Analyzed 
[Units: Participants]
 192   176 
Number of Participants With a New, Non-HIV Related Serious Adverse Event 
[Units: Participants]
 97   88 


Statistical Analysis 1 for Number of Participants With a New, Non-HIV Related Serious Adverse Event
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.92
Hazard Ratio (HR) [4] 1.008
95% Confidence Interval 0.75 to 1.35
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Time-to-event (Kaplan-Meier) and stratified log-rank test was used for the comparison
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  The comparison was Standard-ART (standard) vs Mega-ART (intensification)



5.  Secondary:   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 ]

Measure Type Secondary
Measure Title Number of Participants With New, Non-HIV Related Serious Adverse Event
Measure Description New, on-study non-HIV related Serious Adverse events were compared between ARDFP (interruption) and No ARDFP (continuation)
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  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
ARDFP This includes participants randomized to ARDFP (ARDFP+Standard-ART or ARDFP+Mega-ART)
No ARDFP This includes participants randomized to No ARDFP (No ARDFP+Standard-ART or No ARDFP+Mega-ART)

Measured Values
   ARDFP   No ARDFP 
Participants Analyzed 
[Units: Participants]
 164   175 
Number of Participants With New, Non-HIV Related Serious Adverse Event 
[Units: Participants]
 84   92 


Statistical Analysis 1 for Number of Participants With New, Non-HIV Related Serious Adverse Event
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.68
Hazard Ratio (HR) [4] 1.08
95% Confidence Interval 0.8 to 1.46
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Time-to-event (Kaplan-Meier) and stratified log-rank test was used for the comparison.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  The comparison was ARDFP (interruption) vs No ARDFP (continuation) of ART




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information