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Evaluation of Kaletra Therapy Over the Long-term

This study has been completed.
Sponsor:
Information provided by:
Abbott
ClinicalTrials.gov Identifier:
NCT01083810
First received: February 26, 2010
Last updated: August 9, 2011
Last verified: August 2011
Results First Received: June 30, 2011  
Study Type: Observational
Study Design: Observational Model: Case-Only;   Time Perspective: Prospective
Condition: Human Immunodeficiency Virus
Intervention: Drug: Lopinavir/Ritonavir (Kaletra)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
These three groups of participants with HIV-1 infection were at first registered as three different studies: KAL1RO (this study, NCT01083810, n=137), KAL2RO /KAL5RO (NCT01083836, n=92), and KAL6RO (NCT01081470, n=55) but were now reconciled under KAL1RO (NCT01083810) as a single study with three reporting groups.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Participant Flow:   Overall Study
    Therapy-naive   Pre-treated   Non-B
STARTED   137   92   55 
COMPLETED   72   47   35 
NOT COMPLETED   65   45   20 
Lost to Follow-up                23                11                4 
Adverse Event                15                11                4 
Withdrawal by Subject                7                2                4 
Reason not reported                6                1                1 
Non-compliance                4                7                2 
Simplification                4                1                0 
Death                2                2                3 
Co-morbidities                1                0                0 
Participation in study                1                0                0 
Therapy break                1                2                2 
Virologic failure                1                8                0 



  Baseline Characteristics
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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
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.
Total Total of all reporting groups

Baseline Measures
   Therapy-naive   Pre-treated   Non-B   Total 
Overall Participants Analyzed 
[Units: Participants]
 137   92   55   284 
Age, Customized 
[Units: Participants]
       
>= 18 years of age (exact age not reported)   137   92   55   284 
Gender, Customized 
[Units: Participants]
       
Female   17   11   20   48 
Male   119   81   35   235 
Gender not reported   1   0   0   1 
Region of Enrollment 
[Units: Participants]
       
Germany   137   92   55   284 


  Outcome Measures
  Hide All Outcome Measures

1.  Primary:   Number of Patients With Virus That Develop Mutations Conferring Resistance to Lopinavir/Ritonavir, NRTIs or NNRTIs   [ Time Frame: Baseline and at any timepoint where testing is possible ]

Measure Type Primary
Measure Title Number of Patients With Virus That Develop Mutations Conferring Resistance to Lopinavir/Ritonavir, NRTIs or NNRTIs
Measure Description Standard genotypic resistance assays were developed for HIV-1 viral load levels greater than 500 to 1000 copies per milliliter (mL). All 3 protocols recommended this testing be done at Baseline prior to lopinavir/ritonavir therapy and (if possible) in cases of virologic failure. The exact timing varied and depended on whether there was an adequate viral load and physician clinical judgment. Participants with resistance to lopinavir/ritonavir, nucleoside reverse transcriptase inhibitors (NRTI) or non-nucleoside reverse transcriptase inhibitors (NNRTI) at Baseline and follow-up are reported.
Time Frame Baseline and at any timepoint where testing is possible  
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.
All participants with resistance testing at baseline and follow-up are presented.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Number of Patients With Virus That Develop Mutations Conferring Resistance to Lopinavir/Ritonavir, NRTIs or NNRTIs 
[Units: Participants]
     
Genotypic resistance testing performed at Baseline   137   68   55 
Complete resistance testing results at Baseline   122   68   55 
>Resistance to lopinavir/ritonavir at Baseline   0   2   0 
>Partial resistance to NRTI at Baseline   5   0   0 
>Partial resistance to NNRTI at Baseline   0   0   0 
Underwent resistance testing at follow-up   2   2   2 
>Resistance to lopinavir/ritonavir*   0   1   0 
>>Resistance to NRTIs   0   1   0 
>>Resistance to NNRTIs   0   0   0 
*No baseline results avail for this participant   NA [1]   1   NA [1] 
[1] NA=not applicable to this subgroup.

No statistical analysis provided for Number of Patients With Virus That Develop Mutations Conferring Resistance to Lopinavir/Ritonavir, NRTIs or NNRTIs



2.  Secondary:   Percentage of Patients With HIV-1 RNA <50 Copies/ml   [ Time Frame: Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks ]

Measure Type Secondary
Measure Title Percentage of Patients With HIV-1 RNA <50 Copies/ml
Measure Description All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 ribonucleic acid (RNA) less than 50 copies/mL at each time point is presented by subgroup.
Time Frame Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks  
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.
All participants with HIV-1 RNA measurements at Baseline and any subsequent time point are presented, including those who discontinued due to virologic failure.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Percentage of Patients With HIV-1 RNA <50 Copies/ml 
[Units: Percentage of participants]
     
Baseline   0   3   0 
Week 4   7   26   5 
Week 12   44   38   42 
Week 24   69   58   74 
Week 36   75   60   76 
Week 48   83   67   80 
Week 60   78   65   79 
Week 72   89   62   83 
Week 84   87   66   88 
Week 96   90   58   77 
Week 108   81   66   87 
Week 120   85   63   88 
Week 132   87   52   95 
Week 144   88   65   100 
Week 156   NA [1]   48   100 
Week 168   NA [1]   52   91 
Week 180   NA [1]   53   83 
Week 192   NA [1]   45   100 
Week 204   NA [1]   41   100 
Week 216   NA [1]   50   100 
Week 228   NA [1]   44   75 
Week 240   NA [1]   38   100 
[1] Values not available (NA) as data were collected out to Week 144 in the subgroup of therapy-naive participants.

No statistical analysis provided for Percentage of Patients With HIV-1 RNA <50 Copies/ml



3.  Secondary:   Percentage of Patients With HIV-1 RNA 50 to <200 Copies/ml   [ Time Frame: Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks ]

Measure Type Secondary
Measure Title Percentage of Patients With HIV-1 RNA 50 to <200 Copies/ml
Measure Description All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 RNA levels of 50 to less than 200 copies/mL at each time point is presented by subgroup.
Time Frame Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks  
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.
All participants with HIV-1 RNA measurements at Baseline and any subsequent time point are presented, including those who discontinued due to virologic failure.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Percentage of Patients With HIV-1 RNA 50 to <200 Copies/ml 
[Units: Percentage of participants]
     
Baseline   1   5   0 
Week 4   17   15   14 
Week 12   32   15   25 
Week 24   22   20   18 
Week 36   18   9   10 
Week 48   10   12   5 
Week 60   13   10   6 
Week 72   5   17   3 
Week 84   9   13   6 
Week 96   6   9   10 
Week 108   14   8   4 
Week 120   5   3   4 
Week 132   3   13   0 
Week 144   0   0   0 
Week 156   NA [1]   0   0 
Week 168   NA [1]   0   0 
Week 180   NA [1]   5   8 
Week 192   NA [1]   5   0 
Week 204   NA [1]   6   0 
Week 216   NA [1]   10   0 
Week 228   NA [1]   0   25 
Week 240   NA [1]   0   0 
[1] Values not available (NA) as data were collected out to Week 144 in the subgroup of therapy-naive participants.

No statistical analysis provided for Percentage of Patients With HIV-1 RNA 50 to <200 Copies/ml



4.  Secondary:   Percentage of Patients With HIV-1 RNA 200 to <500 Copies/ml   [ Time Frame: Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks ]

Measure Type Secondary
Measure Title Percentage of Patients With HIV-1 RNA 200 to <500 Copies/ml
Measure Description All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with HIV-1 RNA levels of 200 to less than 500 copies/mL at each time point is presented by subgroup.
Time Frame Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks  
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.
All participants with HIV-1 RNA measurements at Baseline and any subsequent time point are presented, including those who discontinued due to virologic failure.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Percentage of Patients With HIV-1 RNA 200 to <500 Copies/ml 
[Units: Percentage of participants]
     
Baseline   0   3   0 
Week 4   18   12   19 
Week 12   12   15   17 
Week 24   3   6   4 
Week 36   1   9   6 
Week 48   1   0   13 
Week 60   2   6   9 
Week 72   0   6   8 
Week 84   2   5   3 
Week 96   0   7   7 
Week 108   0   0   0 
Week 120   2   9   0 
Week 132   3   0   0 
Week 144   0   10   0 
Week 156   NA [1]   10   0 
Week 168   NA [1]   10   0 
Week 180   NA [1]   0   8 
Week 192   NA [1]   10   0 
Week 204   NA [1]   0   0 
Week 216   NA [1]   0   0 
Week 228   NA [1]   6   0 
Week 240   NA [1]   6   0 
[1] Values not available (NA) as data were collected out to Week 144 in the subgroup of therapy-naive participants.

No statistical analysis provided for Percentage of Patients With HIV-1 RNA 200 to <500 Copies/ml



5.  Secondary:   Percentage of Patients With HIV-1 RNA >500 Copies/ml   [ Time Frame: Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks ]

Measure Type Secondary
Measure Title Percentage of Patients With HIV-1 RNA >500 Copies/ml
Measure Description All 3 protocols recommended that HIV viral load tests be performed at Baseline and each study visit. Study visits were to occur at approximately Weeks 4, 12, and 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. The percentage of participants with more than 500 HIV-1 RNA copies/mL at each time point is presented by subgroup.
Time Frame Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks  
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.
All participants with HIV-1 RNA measurements at Baseline and any subsequent time point are presented, including those who discontinued due to virologic failure.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Percentage of Patients With HIV-1 RNA >500 Copies/ml 
[Units: Percentage of participants]
     
Baseline   99   89   100 
Week 4   59   46   63 
Week 12   13   32   15 
Week 24   6   17   4 
Week 36   6   23   8 
Week 48   6   21   3 
Week 60   7   18   6 
Week 72   5   15   6 
Week 84   2   16   3 
Week 96   4   26   7 
Week 108   5   26   9 
Week 120   7   26   8 
Week 132   8   36   5 
Week 144   13   26   0 
Week 156   NA [1]   43   0 
Week 168   NA [1]   38   9 
Week 180   NA [1]   42   0 
Week 192   NA [1]   40   0 
Week 204   NA [1]   53   0 
Week 216   NA [1]   40   0 
Week 228   NA [1]   50   0 
Week 240   NA [1]   56   0 
[1] Values not available (NA) as data were collected out to Week 144 in the subgroup of therapy-naive participants.

No statistical analysis provided for Percentage of Patients With HIV-1 RNA >500 Copies/ml



6.  Secondary:   Change in Absolute CD4 Cell Count [CD4+ Cells/µL]   [ Time Frame: Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks ]

Measure Type Secondary
Measure Title Change in Absolute CD4 Cell Count [CD4+ Cells/µL]
Measure Description The evolution of participants' CD4-positive (CD4+) T-lymphocyte counts after starting the lopinavir/ritonavir-containing regimen was to be assessed by measuring the number of CD4+ cells at baseline and each subsequent study visit. Study visits were to occur at approximately Weeks 4, 12, 24, followed by 12-week intervals up to Week 144 in therapy-naive participants and up to Week 240 in the pre-treated and non-B subtype groups. CD4+ cell count results are reported as the change from Baseline in the absolute number of CD4+ cells per microliter.
Time Frame Baseline, Week 4, 12, 24, followed by 12-week intervals up to 144/240 weeks  
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.
All participants with CD4+ measurements at Baseline and any subsequent time point are included.

Reporting Groups
  Description
Therapy-naive Participants who had not received prior antiretroviral drug therapy.
Pre-treated Participants that had previously received antiretroviral therapy, but were protease inhibitor naive.
Non-B Participants infected with non-B subtypes of HIV-1.

Measured Values
   Therapy-naive   Pre-treated   Non-B 
Participants Analyzed 
[Units: Participants]
 137   92   55 
Change in Absolute CD4 Cell Count [CD4+ Cells/µL] 
[Units: CD4+ cells/µL]
Mean (Standard Deviation)
     
Baseline   0  (0)   0  (0)   0  (0) 
Week 4   140  (145)   68  (122)   131  (203) 
Week 12   146  (130)   98  (204)   92  (117) 
Week 24   193  (170)   106  (209)   128  (139) 
Week 36   211  (203)   144  (203)   148  (134) 
Week 48   240  (162)   114  (200)   204  (173) 
Week 60   266  (185)   144  (196)   222  (206) 
Week 72   248  (201)   179  (193)   259  (204) 
Week 84   295  (248)   181  (176)   226  (161) 
Week 96   296  (190)   192  (223)   239  (205) 
Week 108   329  (204)   223  (227)   255  (195) 
Week 120   316  (177)   217  (206)   275  (199) 
Week 132   313  (237)   213  (167)   325  (218) 
Week 144   292  (163)   251  (244)   320  (131) 
Week 156   NA [1]   220  (183)   404  (162) 
Week 168   NA [1]   190  (156)   426  (189) 
Week 180   NA [1]   174  (225)   422  (135) 
Week 192   NA [1]   192  (186)   474  (162) 
Week 204   NA [1]   131  (244)   420  (172) 
Week 216   NA [1]   210  (243)   395  (230) 
Week 228   NA [1]   208  (345)   399  (93) 
Week 240   NA [1]   179  (185)   542  (188) 
[1] Values not available (NA) as data were collected out to Week 144 in the subgroup of therapy-naive participants.

No statistical analysis provided for Change in Absolute CD4 Cell Count [CD4+ Cells/µL]




  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
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Global Medical Services
Organization: Abbott
phone: 1-800-633-9110



Responsible Party: Dr. Stefan Simianer, Medical Director, Medical Department, Abbott Germany (Wiesbaden)
ClinicalTrials.gov Identifier: NCT01083810     History of Changes
Obsolete Identifiers: NCT01081470, NCT01083836
Other Study ID Numbers: KAL 1 RO
Study First Received: February 26, 2010
Results First Received: June 30, 2011
Last Updated: August 9, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices