Study Comparing Lopinavir/Ritonavir (LPV/r) + Emtricitabine/Tenofovir Disoproxil Fumarate (FTC/TDF) With a Nucleoside Sparing Regimen Consisting of Lopinavir/Ritonavir + Raltegravir (RAL) (PROGRESS)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Abbott
ClinicalTrials.gov Identifier:
NCT00711009
First received: July 3, 2008
Last updated: February 13, 2012
Last verified: February 2012
Results First Received: November 16, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus Infection
Interventions: Drug: lopinavir/ritonavir (LPV/r)
Drug: emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)
Drug: raltegravir (RAL)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
3 additional participants were randomized but did not receive study drug and therefore were not included in the analyses.

Reporting Groups
  Description
LPV/r + FTC/TDF lopinavir/ritonavir 400/100 mg tablet twice-daily + co-formulated emtricitabine/tenofovir disoproxil fumarate 200/300 mg once-daily
LPV/r + RAL lopinavir/ritonavir 400/100 mg tablet twice-daily + raltegravir 400 mg twice-daily

Participant Flow:   Overall Study
    LPV/r + FTC/TDF     LPV/r + RAL  
STARTED     105     101  
COMPLETED     90     82  
NOT COMPLETED     15     19  
Adverse Event/HIV-Related Event                 4                 5  
Withdrawal by Subject                 4                 2  
Lost to Follow-up                 3                 9  
Participant Noncompliant                 0                 1  
Virologic Failure                 2                 1  
Pregnancy                 1                 0  
Site closing                 0                 1  
Dose adjustment                 1                 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
LPV/r + FTC/TDF lopinavir/ritonavir 400/100 mg tablet twice-daily + co-formulated emtricitabine/tenofovir disoproxil fumarate 200/300 mg once-daily
LPV/r + RAL lopinavir/ritonavir 400/100 mg tablet twice-daily + raltegravir 400 mg twice-daily
Total Total of all reporting groups

Baseline Measures
    LPV/r + FTC/TDF     LPV/r + RAL     Total  
Number of Participants  
[units: participants]
  105     101     206  
Age  
[units: years]
Mean ± Standard Deviation
  39.4  ± 11.24     39.8  ± 9.94     39.6  ± 10.60  
Gender  
[units: participants]
     
Female     19     13     32  
Male     86     88     174  
Race/Ethnicity, Customized  
[units: participants]
     
American Indian or Alaska Native     0     0     0  
Asian     1     3     4  
Native Hawaiian or Other Pacific Islander     0     0     0  
Black or African American     22     22     44  
White     81     74     155  
More than one race     0     1     1  
Unknown or Not Reported     0     0     0  
Other     1     1     2  
Region of Enrollment  
[units: participants]
     
North America     61     59     120  
Europe     44     42     86  
Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Level  
[units: log10┬ácopies/milliliter]
Mean ± Standard Deviation
  4.3  ± 0.76     4.2  ± 0.83     4.2  ± 0.79  
CD4+ T-Cell Counts  
[units: cells/microliter]
Mean ± Standard Deviation
  297.6  ± 166.66     289.3  ± 149.03     293.5  ± 157.93  



  Outcome Measures
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1.  Primary:   Percentage of Participants Responding (Plasma HIV-1 Ribonucleic Acid [RNA] Levels Less Than 40 Copies/Milliliter [mL]) at Week 48 Based on the Food and Drug Administration (FDA) Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Baseline to Week 48 ]

2.  Primary:   Percentage of Participants With Moderate or Severe Treatment-emergent, Drug-related Adverse Events   [ Time Frame: Week 96 ]

3.  Primary:   Primary Outcome: Percentage of Participants With Potentially Clinically Significant Laboratory Values   [ Time Frame: Baseline to Week 96 ]

4.  Secondary:   Percentage of Participants Responding (Plasma HIV-1 RNA Levels Below 40 Copies/Milliliter [mL]) at Each Visit Based on the FDA Time to Loss of Virologic Response (TLOVR) Algorithm   [ Time Frame: Baseline to Week 96 ]

5.  Secondary:   Mean Change in CD4+ T-Cell Counts From Baseline to Each Visit   [ Time Frame: Baseline to Week 96 ]

6.  Secondary:   Time to Loss of Virologic Response - Percentage of Participants Still Categorized as Responders at Day 672   [ Time Frame: Baseline to Week 96 ]

7.  Secondary:   Number of Participants Who Developed Resistance to Each Drug in the Study Regimen, as Defined by the International AIDS Society-USA (IAS-USA) Panel.   [ Time Frame: Baseline to Week 96 ]

8.  Secondary:   Number of Participants Who Developed Resistance, Defined Conservatively, to Lopinavir   [ Time Frame: Baseline to Week 96 ]

9.  Secondary:   Change From Baseline on Physical Component Score of the Medical Outcomes Study HIV Health Survey   [ Time Frame: Baseline to Week 96 ]

10.  Secondary:   Change From Baseline on Mental Component of Medical Outcomes Study HIV Health Survey   [ Time Frame: Baseline to Week 96 ]

11.  Secondary:   Score on Effectiveness Scale of Treatment Satisfaction Questionnaire for Medication (TSQM)   [ Time Frame: Week 96 ]

12.  Secondary:   Score on Side Effects Scale of Treatment Satisfaction Questionnaire for Medication   [ Time Frame: Week 96 ]

13.  Secondary:   Score on Global Satisfaction Scale of Treatment Satisfaction Questionnaire for Medication   [ Time Frame: Week 96 ]

14.  Secondary:   Mean Change From Baseline in Hemoglobin (Grams/Liter)   [ Time Frame: Baseline to Week 96 ]

15.  Secondary:   Mean Change From Baseline in Hematocrit (Fraction)   [ Time Frame: Baseline to Week 96 ]

16.  Secondary:   Mean Change From Baseline in Red Blood Cell Count (x 10^12/Liter)   [ Time Frame: Baseline to Week 96 ]

17.  Secondary:   Mean Change From Baseline in Platelet Count (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

18.  Secondary:   Mean Change From Baseline in White Blood Cell Count (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

19.  Secondary:   Mean Change From Baseline in Neutrophils (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

20.  Secondary:   Mean Change From Baseline in Lymphocytes (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

21.  Secondary:   Mean Change From Baseline in Monocytes (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

22.  Secondary:   Mean Change From Baseline in Eosinophils (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

23.  Secondary:   Mean Change From Baseline in Basophils (x 10^9/Liter)   [ Time Frame: Baseline to Week 96 ]

24.  Secondary:   Mean Change From Baseline in Alanine Aminotransferase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]

25.  Secondary:   Mean Change From Baseline in Aspartate Aminotransferase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]

26.  Secondary:   Mean Change From Baseline in Alkaline Phosphatase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]

27.  Secondary:   Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]
  Hide Outcome Measure 27

Measure Type Secondary
Measure Title Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)
Measure Description No text entered.
Time Frame Baseline to Week 96  
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.
Participants who had values at Baseline and Week 96 were included in the analysis.

Reporting Groups
  Description
LPV/r + FTC/TDF lopinavir/ritonavir 400/100 mg tablet twice-daily + co-formulated emtricitabine/tenofovir disoproxil fumarate 200/300 mg once-daily
LPV/r + RAL lopinavir/ritonavir 400/100 mg tablet twice-daily + raltegravir 400 mg twice-daily

Measured Values
    LPV/r + FTC/TDF     LPV/r + RAL  
Number of Participants Analyzed  
[units: participants]
  90     82  
Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)  
[units: units/liter]
Mean ± Standard Deviation
  398.9  ± 3381.10     157.2  ± 1081.24  

No statistical analysis provided for Mean Change From Baseline in Creatine Phosphokinase (Units/Liter)



28.  Secondary:   Mean Change From Baseline in Total Bilirubin (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

29.  Secondary:   Mean Change From Baseline in Creatinine (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

30.  Secondary:   Mean Change From Baseline in Blood Urea Nitrogen (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

31.  Secondary:   Mean Change From Baseline in Uric Acid (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

32.  Secondary:   Mean Change From Baseline in Inorganic Phosphate (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

33.  Secondary:   Mean Change From Baseline in Calcium (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

34.  Secondary:   Mean Change From Baseline in Sodium (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

35.  Secondary:   Mean Change From Baseline in Potassium (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

36.  Secondary:   Mean Change From Baseline in Chloride (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

37.  Secondary:   Mean Change From Baseline in Bicarbonate (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

38.  Secondary:   Mean Change From Baseline in Albumin (Grams/Liter)   [ Time Frame: Baseline to Week 96 ]

39.  Secondary:   Mean Change From Baseline in Total Protein (Grams/Liter)   [ Time Frame: Baseline to Week 96 ]

40.  Secondary:   Mean Change From Baseline in Cholesterol (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

41.  Secondary:   Mean Change From Baseline in High Density Lipoprotein Cholesterol (HDL) (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

42.  Secondary:   Mean Change From Baseline in Low Density Lipoprotein (LDL) (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

43.  Secondary:   Mean Change From Baseline in Low Density Lipoprotein (LDL): High Density Lipoprotein (HDL) Ratio (Ratio)   [ Time Frame: Baseline to Week 96 ]

44.  Secondary:   Mean Change From Baseline in Triglycerides (Micromoles/Liter)   [ Time Frame: Baseline to Week 96 ]

45.  Secondary:   Mean Change From Baseline in Calculated Creatinine Clearance (Milliliters/Second)   [ Time Frame: Baseline to Week 96 ]

46.  Secondary:   Mean Change From Baseline in Fasting Glucose (Millimoles/Liter)   [ Time Frame: Baseline to Week 96 ]

47.  Secondary:   Mean Change From Baseline in Lactate Dehydrogenase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]

48.  Secondary:   Mean Change From Baseline in Lipase (Units/Liter)   [ Time Frame: Baseline to Week 96 ]

49.  Secondary:   Mean Change From Baseline in Magnesium (Millimoles/Liter)   [ Time Frame: Baseline to Week 96 ]

50.  Secondary:   Mean Change From Baseline in Adiponectin (Micrograms/Milliliter)   [ Time Frame: Baseline to Week 96 ]

51.  Secondary:   Mean Change From Baseline in Interleukin-6 (Nanograms/Liter)   [ Time Frame: Baseline to Week 96 ]

52.  Secondary:   Mean Change From Baseline in Lactate (Millimoles/Liter)   [ Time Frame: Baseline to Week 96 ]

53.  Secondary:   Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-1 (Picograms/Milliliter)   [ Time Frame: Baseline to Week 96 ]

54.  Secondary:   Mean Change From Baseline in Soluble Tumor Necrosis Factor Receptor-2 (Picograms/Milliliter)   [ Time Frame: Baseline to Week 96 ]

55.  Secondary:   Mean Change From Baseline in Leptin (Nanograms/Milliliter)   [ Time Frame: Baseline to Week 96 ]

56.  Secondary:   Mean Change From Baseline in Insulin (Picomoles/Liter)   [ Time Frame: Baseline to Week 96 ]

57.  Secondary:   Mean Change From Baseline in Urine Specific Gravity   [ Time Frame: Baseline to Week 96 ]

58.  Secondary:   Mean Change From Baseline in Urine pH   [ Time Frame: Baseline to Week 96 ]

59.  Secondary:   Mean Change From Baseline in Sitting Systolic Blood Pressure (mm Hg)   [ Time Frame: Baseline to Week 96 ]

60.  Secondary:   Mean Change From Baseline in Sitting Diastolic Blood Pressure (mm Hg)   [ Time Frame: Baseline to Week 96 ]

61.  Secondary:   Mean Change From Baseline in Sitting Heart Rate (Beats Per Minute)   [ Time Frame: Baseline to Week 96 ]

62.  Secondary:   Mean Change From Baseline in Weight (kg)   [ Time Frame: Baseline to Week 96 ]

63.  Secondary:   Mean Change From Baseline in Temperature (°F)   [ Time Frame: Baseline to Week 96 ]

64.  Secondary:   Mean Change From Baseline in Chest Measurement (cm)   [ Time Frame: Baseline to Week 96 ]

65.  Secondary:   Mean Change From Baseline in Waist Measurement (cm)   [ Time Frame: Baseline to Week 96 ]

66.  Secondary:   Mean Change From Baseline in Mid-Arm Measurement (cm)   [ Time Frame: Baseline to Week 96 ]

67.  Secondary:   Mean Change From Baseline in Hips Measurement (cm)   [ Time Frame: Baseline to Week 96 ]

68.  Secondary:   Mean Change From Baseline in Mid-Thigh Measurement (cm)   [ Time Frame: Baseline to Week 96 ]

69.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Fat (Grams)   [ Time Frame: Baseline to Week 96 ]

70.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Lean Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

71.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Upper Extremity Total Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

72.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Fat (Grams)   [ Time Frame: Baseline to Week 96 ]

73.  Secondary:   Mean Change From Baseline in DEXA Scan of Lower Extremity Lean Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

74.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Lower Extremity Total Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

75.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Fat (Grams)   [ Time Frame: Baseline to Week 96 ]

76.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Lean Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

77.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Trunk Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

78.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Fat (Grams)   [ Time Frame: Baseline to Week 96 ]

79.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Lean Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

80.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Total Body Mass (Grams)   [ Time Frame: Baseline to Week 96 ]

81.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Content (Grams)   [ Time Frame: Baseline to Week 96 ]

82.  Secondary:   Mean Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan of Bone Mineral Density (Grams/cm^2)   [ Time Frame: Baseline to Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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