A Study to Compare Brachial Artery Reactivity and Cardiovascular Risk of a Treatment Simplification by Darunavir/Ritonavir (DRV/r) 800/100 mg Versus a Triple Combination Therapy Containing DRV/r in HIV-1 Infected Patients (MONARCH)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag S.p.A.
ClinicalTrials.gov Identifier:
NCT01391013
First received: June 23, 2011
Last updated: May 22, 2013
Last verified: May 2013
Results First Received: February 13, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Human Immunodeficiency Virus 1
Interventions: Drug: Darunavir(DRV)
Drug: Ritonavir
Drug: 2 nucleoside reverse transcriptase inhibitors (NRTIs)

  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
30 participants were enrolled at a single site in Italy.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
30 participants were randomly assigned to 2 treatment groups (15 participants in each group) and all participants received the study medication.

Reporting Groups
  Description
Monotherapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) administered once daily
Combination Therapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs)

Participant Flow:   Overall Study
    Monotherapy     Combination Therapy  
STARTED     15     15  
COMPLETED     15     15  
NOT COMPLETED     0     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
Monotherapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) administered once daily
Combination Therapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs)
Total Total of all reporting groups

Baseline Measures
    Monotherapy     Combination Therapy     Total  
Number of Participants  
[units: participants]
  15     15     30  
Age  
[units: Years]
Median ( Inter-Quartile Range )
  44.8  
  ( 34.5 to 55.1 )  
  43.0  
  ( 35.0 to 46.8 )  
  44.6  
  ( 35.0 to 47.4 )  
Gender  
[units: Participants]
     
Female     3     4     7  
Male     12     11     23  
Race/Ethnicity, Customized  
[units: Participants]
     
White     14     15     29  
Black     1     0     1  



  Outcome Measures
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1.  Primary:   Change From Baseline to Week 24 in Brachial Artery Flow Mediated Vasodilatation (FMD): Median Change in FMD (%)   [ Time Frame: Baseline (Day 1 of Week 1) to Week 24 ]

2.  Secondary:   Change From Baseline to Week 48 in Brachial Artery FMD: Median Change in FMD (%)   [ Time Frame: Baseline to Week 48 ]

3.  Secondary:   Number of Participants With a Human Immunodeficiency Virus- Ribonucleic Acid (HIV-RNA) Greater Than or Equal to 50 Copies/mL   [ Time Frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52) ]

4.  Secondary:   Change From Baseline to Week 48 in Circulating Endothelial Cells   [ Time Frame: Baseline to Week 48 ]

5.  Secondary:   Change From Baseline to Week 48 in Precursors of Circulating Endothelial Cells   [ Time Frame: Baseline to Week 48 ]

6.  Secondary:   Change From Baseline in Mean Low-density Lipoprotein (LDL) Cholesterol at Week 24 and Week 48: Median Change in LDL   [ Time Frame: Baseline (Day1 of Week 1), Week 24, and Week 48 ]

7.  Secondary:   Change From Baseline in Mean High-density Lipoprotein (HDL) Cholesterol at Week 24 and Week 48: Median Change in HDL   [ Time Frame: Baseline, Week 24, and Week 48 ]

8.  Secondary:   Change From Baseline in Mean Triglycerides at Week 24 and Week 48: Median Change in Triglycerides   [ Time Frame: Baseline, Week 24, and Week 48 ]

9.  Secondary:   Change From Baseline in Insulin Sensitivity at Week 24 and Week 48: Median Change in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)   [ Time Frame: Baseline, Week 24, and Week 48 ]

10.  Secondary:   Change From Baseline in Mean Framingham Risk Score at Week 24 and Week 48: Medican Change in Framingham Risk Score   [ Time Frame: Baseline, Week 24, and Week 48 ]

11.  Secondary:   Change From Baseline to Week 48 in Leg Fat Content: Median Change in Leg Fat (Total)   [ Time Frame: Baseline to Week 48 ]

12.  Secondary:   Change From Baseline to Week 48 in Visceral Fat Content in Abdomen: Median Change in Visceral Abdominal Tissue (VAT)   [ Time Frame: Baseline to Week 48 ]

13.  Secondary:   Change From Baseline to Week 48 in Femoral Neck T Score: Median Change in Femoral Neck T Score   [ Time Frame: Baseline to Week 48 ]

14.  Secondary:   Change From Baseline to Week 48 in Femoral Neck Z Score: Median Change in Femoral Neck Z Score   [ Time Frame: Baseline to Week 48 ]

15.  Secondary:   Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score   [ Time Frame: Baseline to Week 48 ]
  Hide Outcome Measure 15

Measure Type Secondary
Measure Title Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score
Measure Description T score is used to calculate bone mineral density (calcium and other types of minerals) in an area of the bone. T score is the number of standard deviations above or below the mean for a healthy 30 year old adult of the same sex and ethnicity as a participant. This score is calculated from participant's age, gender and race and skeletal site. T score has a mean of ‘50’ and a standard deviation of ‘10’. T score lower than its mean indicate low bone mineral density.
Time Frame Baseline to Week 48  
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.
Participants who were randomized, who received the study medication, and who contributed any efficacy data after the start of study treatment.

Reporting Groups
  Description
Monotherapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) administered once daily
Combination Therapy 2 tablets of darunavir (2 X 400 mg) and 1 tablet ritonavir (100 mg) once daily + 2 nucleoside reverse transcriptase inhibitors (NRTIs)

Measured Values
    Monotherapy     Combination Therapy  
Number of Participants Analyzed  
[units: participants]
  15     15  
Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score  
[units: T score]
Median ( Inter-Quartile Range )
  0.1  
  ( 0.0 to 0.3 )  
  0.0  
  ( -0.2 to 0.1 )  


Statistical Analysis 1 for Change From Baseline to Week 48 in Lumbar T Score: Median Change in Lumbar T Score
Groups [1] All groups
Method [2] Nonparametric Wilcoxon rank sum test
P Value [3] 0.03
[1] Additional details about the analysis, such as null hypothesis and power calculation:
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[2] Other relevant method information, such as adjustments or degrees of freedom:
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[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
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16.  Secondary:   Change From Baseline to Week 48 in Lumbar Z Score: Median Change in Lumbar Z Score   [ Time Frame: Baseline to Week 48 ]

17.  Secondary:   Change From Baseline in Cluster of Differentiation 4 (CD4) Count Over Week 48   [ Time Frame: Screening (Week -4), Week 1 (Day 1), Week 4, Week 12, Week 24, Week 36, Week 48, and follow-up (Week 52) ]


  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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  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 Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Therapeutic Area Medical Manager
Organization: Jan-Cil Italy
phone: 39 02 2510589 ext NA


No publications provided


Responsible Party: Janssen-Cilag S.p.A.
ClinicalTrials.gov Identifier: NCT01391013     History of Changes
Other Study ID Numbers: CR017575, TMC114HIV3017, TMC-C-07-IT-016
Study First Received: June 23, 2011
Results First Received: February 13, 2013
Last Updated: May 22, 2013
Health Authority: Italy: AIFA - Italian Medicines Agency