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Rifampin-Based Tuberculosis Treatment Versus Rifabutin-Based Tuberculosis Treatment in Persons With HIV

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ClinicalTrials.gov Identifier: NCT01601626
Recruitment Status : Terminated (The study was stopped early due to feasibility concerns.)
First Posted : May 18, 2012
Results First Posted : February 13, 2018
Last Update Posted : February 13, 2018
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
AIDS Clinical Trials Group

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: HIV Infection
Tuberculosis
Interventions: Drug: Standard-dose Lopinavir/Ritonavir
Drug: Double-dose Lopinavir/Ritonavir
Drug: Raltegravir
Drug: Isoniazid
Drug: Pyridoxine
Drug: Pyrazinamide
Drug: Ethambutol
Drug: Rifabutin
Drug: Rifampin

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study participants were recruited at 9 sites from 5 countries (2 each from Brazil, Haiti, Peru, and South Africa and 1 from Kenya) between July 2013 and February 2016.

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
A: Standard-dose LPV/r w/RBT

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

B: Double-dose LPV/r w/RIF

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

C: Standard-Dose LPV/r + RAL w/RBT

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.


Participant Flow:   Overall Study
    A: Standard-dose LPV/r w/RBT   B: Double-dose LPV/r w/RIF   C: Standard-Dose LPV/r + RAL w/RBT
STARTED   24   24   23 
COMPLETED   21   19   21 
NOT COMPLETED   3   5   2 
Death                1                1                1 
Lost to Follow-up                1                2                0 
Unable to Get to Clinic                0                1                0 
Withdrawal by Subject                0                1                1 
Not Willing to Adhere to Requirements                1                0                0 



  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.
All randomized participants were included.

Reporting Groups
  Description
A: Standard-dose LPV/r w/RBT

ART: standard-dose LPV/r twice daily + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + two NRTIs.

B: Double-dose LPV/r w/RIF

ART: double-dose LPV/r twice daily + 2 NRTIs. Anti-TB therapy: isoniazid, rifampin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + 2 NRTIs.

C: Standard-Dose LPV/r + RAL w/RBT

ART: standard-dose LPV/r twice daily + RAL + two NRTIs. Anti-TB therapy: isoniazid, rifabutin, ethambutol, pyrazinamide, and pyridoxine daily.

After completion of TB treatment through week 72: standard-dose LPV/r twice daily + RAL + two NRTIs.

Total Total of all reporting groups

Baseline Measures
   A: Standard-dose LPV/r w/RBT   B: Double-dose LPV/r w/RIF   C: Standard-Dose LPV/r + RAL w/RBT   Total 
Overall Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Age 
[Units: Years]
Median (Inter-Quartile Range)
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
   42 
 (33 to 49) 
 35 
 (29 to 41) 
 38 
 (32 to 47) 
 37 
 (32 to 46) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Female      13  54.2%      9  37.5%      15  65.2%      37  52.1% 
Male      11  45.8%      15  62.5%      8  34.8%      34  47.9% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Black of African Origin      7  29.2%      8  33.3%      6  26.1%      21  29.6% 
Black African      8  33.3%      6  25.0%      4  17.4%      18  25.4% 
White      4  16.7%      2   8.3%      6  26.1%      12  16.9% 
Mixed Black      3  12.5%      5  20.8%      3  13.0%      11  15.5% 
Mestizo      2   8.3%      2   8.3%      2   8.7%      6   8.5% 
Mixed, of Predominantly African Ancestry      0   0.0%      0   0.0%      1   4.3%      1   1.4% 
Other      0   0.0%      1   4.2%      1   4.3%      2   2.8% 
Region of Enrollment 
[Units: Participants]
       
Haiti         
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Haiti   6   6   6   18 
Brazil         
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Brazil   8   10   10   28 
South Africa         
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
South Africa   4   3   3   10 
Kenya         
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Kenya   4   3   2   9 
Peru         
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Peru   2   2   2   6 
Qualitative HIV RNA [1] 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Less than 40 copies/mL      4  16.7%      2   8.3%      3  13.0%      9  12.7% 
Greater than or equal to 40 copies/mL      20  83.3%      22  91.7%      20  87.0%      62  87.3% 
[1] The lower limit of quantification of the HIV RNA assay used in the protocol was 40 copies/mL.
Quantitative HIV RNA [1] [2] 
[Units: Log10 copies/mL]
Median (Inter-Quartile Range)
       
Participants Analyzed 
[Units: Participants]
 20   22   20   62 
   4.7 
 (3.4 to 5.6) 
 4.8 
 (4.2 to 5.3) 
 4.2 
 (3.2 to 5.0) 
 4.6 
 (3.5 to 5.3) 
[1] The lower limit of quantification of the HIV RNA assay used in the protocol was 40 copies/mL.
[2] Quantitative HIV RNA was summarized in the participants whose HIV RNA was above the assay's lower limit of quantification.
CD4 Cell Count 
[Units: Cells/mm^3]
Median (Inter-Quartile Range)
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
   128 
 (60 to 234) 
 117 
 (51 to 246) 
 158 
 (73 to 202) 
 130 
 (55 to 231) 
Tuberculosis (TB) Diagnosis Certainty [1] 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Confirmed Pulmonary TB      13  54.2%      8  33.3%      6  26.1%      27  38.0% 
Confirmed Extrapulmonary TB      1   4.2%      1   4.2%      3  13.0%      5   7.0% 
Confirmed Pulmonary and Extrapulmonary TB      1   4.2%      0   0.0%      0   0.0%      1   1.4% 
Probable Pulmonary TB      9  37.5%      15  62.5%      13  56.5%      37  52.1% 
Probable Extrapulmonary TB      0   0.0%      0   0.0%      1   4.3%      1   1.4% 
[1] The protocol document contains the definitions of confirmed and probable for pulmonary and extrapulmonary TB in section 4.1.3.
Acid Fast Bacilli (AFB) Smear 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
Positive      11  45.8%      8  33.3%      6  26.1%      25  35.2% 
Negative      10  41.7%      14  58.3%      16  69.6%      40  56.3% 
No Results Available      3  12.5%      2   8.3%      1   4.3%      6   8.5% 
Mycobacteria Tuberculosis (MTB) Culture 
[Units: Participants]
Count of Participants
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
MTB-Positive      13  54.2%      8  33.3%      9  39.1%      30  42.3% 
MTB-Negative      6  25.0%      13  54.2%      13  56.5%      32  45.1% 
No Results Available      5  20.8%      3  12.5%      1   4.3%      9  12.7% 
Body Mass Index (BMI) 
[Units: Kg/m^2]
Median (Inter-Quartile Range)
       
Participants Analyzed 
[Units: Participants]
 24   24   23   71 
   19.9 
 (18.3 to 22.1) 
 20.4 
 (17.9 to 21.5) 
 18.9 
 (17.9 to 21.5) 
 19.6 
 (17.9 to 21.5) 


  Outcome Measures

1.  Primary:   Percent of Participants Whose HIV Viral Load Was Less Than 400 Copies/mL at Week 48.   [ Time Frame: 48 weeks ]

2.  Secondary:   Percent of Participants Who Experienced Sputum Conversion at Week 8.   [ Time Frame: 8 weeks ]

3.  Secondary:   Percent of Participants Who Experienced TB Treatment Failure   [ Time Frame: After 16 weeks and through week 72 ]

4.  Secondary:   Percent of Participants Who Experienced TB Relapse/Recurrence   [ Time Frame: At or after 24 weeks and through week 72 ]

5.  Secondary:   Percent of Participants Who Experienced TB Relapse/Recurrence and Who Had TB Drug Resistance   [ Time Frame: At or after 24 weeks and through week 72 ]

6.  Secondary:   Percent of Participants Whose HIV Viral Load Was Less Than 50 Copies/mL at Week 48   [ Time Frame: 48 weeks ]

7.  Secondary:   Number of Participants Reporting a Grade 3 or 4 Sign or Symptom   [ Time Frame: After randomization and through week 72 ]

8.  Secondary:   Number of Participants Reporting a Grade 3 or 4 Laboratory Abnormality   [ Time Frame: After randomization and through week 72 ]

9.  Secondary:   Percent of Participants Who Interrupted or Discontinued at Least One HIV Drug Due to Toxicity   [ Time Frame: After randomization and through week 72 ]

10.  Secondary:   Percent of Participants Who Interrupted or Discontinued at Least One TB Drug Due to Toxicity   [ Time Frame: After randomization and through to the discontinuation of the last TB drug ]

11.  Secondary:   Percent of Participants Who Experienced HIV Virologic Failure   [ Time Frame: At weeks 16, 24, 48, and 72 ]

12.  Secondary:   Cumulative Probability of HIV Virologic Failure at Week 72   [ Time Frame: At weeks 16, 24, 48, and 72 ]

13.  Secondary:   Number of Participants Who Experienced MTB IRIS   [ Time Frame: After randomization and through week 72 ]

14.  Secondary:   CD4 Count Change From Baseline to Week 8   [ Time Frame: Baseline and 8 weeks ]

15.  Secondary:   CD4 Count Change From Baseline to Week 24   [ Time Frame: Baseline and 24 weeks ]

16.  Secondary:   CD4 Count Change From Baseline to Week 48   [ Time Frame: Baseline and 48 weeks ]

17.  Secondary:   CD4 Count Change From Baseline to Week 72   [ Time Frame: Baseline and 72 weeks ]

18.  Secondary:   Percent of Participants Who Experienced a New AIDS-defining Illness   [ Time Frame: After randomization and through week 72 ]

19.  Secondary:   Percent of Participants Who Died   [ Time Frame: After randomization and through week 72 ]

20.  Secondary:   Percent of Participants Who Experienced a New AIDS-defining Illness or Died   [ Time Frame: After randomization and through week 72 ]

21.  Other Pre-specified:   LPV Cmax and Cmin in Participants Enrolled in Arms A, B, and C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose ]

22.  Other Pre-specified:   LPV AUC in Participants Enrolled in Arms A, B, and C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, and 6 hours post-dose ]

23.  Other Pre-specified:   RBT Cmax and Cmin in Participants Enrolled in Arms A and C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose ]

24.  Other Pre-specified:   RBT AUC in Participants Enrolled in Arms A and C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose ]

25.  Other Pre-specified:   RAL Cmax and Cmin in Participants Enrolled in Arm C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose ]

26.  Other Pre-specified:   RAL AUC in Participants Enrolled in Arm C   [ Time Frame: At 2 weeks: pre-dose and at 2, 4, 5, 6, and 24 hours post-dose ]


  Serious Adverse Events


  Other Adverse Events


  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
The study was terminated after 71 of 471 participants enrolled. Therefore, the study was under-powered and formal statistical comparisons between study arms were not undertaken as originally planned. Instead, summaries within study arm were provided.


  More Information

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: ACTG Clinicaltrials.gov Coordinator
Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
phone: (301) 628-3313
e-mail: ACTGCT.Gov@s-3.com



Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT01601626     History of Changes
Other Study ID Numbers: ACTG A5290
1U01AI068636 ( U.S. NIH Grant/Contract )
First Submitted: May 16, 2012
First Posted: May 18, 2012
Results First Submitted: January 10, 2018
Results First Posted: February 13, 2018
Last Update Posted: February 13, 2018