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A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies
This study is ongoing, but not recruiting participants.
Study NCT00293267   Information provided by Merck
First Received: February 14, 2006   Last Updated: November 12, 2009   History of Changes
Study Type: Interventional
Study Design: Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment
Condition: HIV Infections
Interventions: Drug: raltegravir potassium
Drug: Comparator: Placebo

  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
Phase III; First Patient In: 22-Mar-2006; Last Patient Last Visit for Week 48: 03-Aug-2007 63 sites (Australia, Belgium, Denmark, France, Germany, Italy, Peru, Portugal, Spain, Switzerland, Taiwan, and Thailand), 61 of which randomized patients.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >1000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase inhibitors and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Participant Flow:   Overall Study
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
STARTED   234     118  
      Treated               232                 118  
      Continuing in Double-Blind               193                 50  
COMPLETED   193[1]   50  
NOT COMPLETED   41     68  
      Never Treated               2                 0  
      Adverse Event               1                 1  
      Death               3                 3  
      Lack of Efficacy               0                 2  
      Lost to Follow-up               1                 1  
      Withdrawal by Subject               1                 1  
      Entered Virological Failure Phase               33                 60  
[1] Does not include patients whom entered the open-label post virological



  Baseline Characteristics
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Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Baseline Measures
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT Total
Number of Participants  
[units: participants]
 		232 118 350
Age  
[units: Years]
Mean ( Full Range ) 		46.1
( 16 to 74 )		 43.7
( 19 to 64 )		 45.3
( 16 to 74 )
Gender  
[units: participants]
 		     
Female 37 15 52
Male 195 103 298
Race/Ethnicity, Customized  
[units: participants]
 		     
White 174 96 270
Black 18 5 23
Asian 14 5 19
Hispanic 6 1 7
Other 20 11 31
Cluster of Differentiation 4 (CD4) Cell Count  
[units: cells/mm^3]
Mean ( Full Range ) 		156
( 1 to 792 )		 153
( 3 to 759 )		 155
( 1 to 792 )
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: copies/mL]
Geometric Mean ( Full Range ) 		40519
( 441 to 750000 )		 31828
( 200 to 750000 )		 37352
( 200 to 750000 )



  Outcome Measures
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1.  Primary:   Proportion of Patients Achieving HIV RNA <400 Copies/mL at Week 16   [ 16 Weeks ]

Measure Type Primary
Measure Title Proportion of Patients Achieving HIV RNA <400 Copies/mL at Week 16
Measure Description Proportion of patients who achieve HIV RNA <400 copies/mL at Week 16
Time Frame 16 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.
No text entered.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		231 118
Proportion of Patients Achieving HIV RNA <400 Copies/mL at Week 16
[units: Participants]
 		178 48

No statistical analysis provided for Proportion of Patients Achieving HIV RNA <400 Copies/mL at Week 16



2.  Secondary:   Change From Baseline in HIV RNA at Week 16   [ Baseline and Week 16 ]

Measure Type Secondary
Measure Title Change From Baseline in HIV RNA at Week 16
Measure Description Mean change from baseline at Week 16 in HIV RNA (log10 copies/mL)
Time Frame Baseline and Week 16  
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.
Observed mean change from baseline in log10 Plasma HIV RNA for each group was calculated using the conventional imputation (replace HIV RNA <400 copies/mL by 400 copies/mL if signal detected, or 200 copies/mL if signal not detected. Missing values: baseline-carry-forward for all failures or discontinued due to lack of efficacy

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		231 118
Change From Baseline in HIV RNA at Week 16
[units: HIV RNA (log10 copies/mL)]
Mean ( 95% Confidence Interval ) 		-1.85
( -1.97 to -1.73 )		 -0.78
( -0.97 to -0.59 )

No statistical analysis provided for Change From Baseline in HIV RNA at Week 16



3.  Secondary:   Change From Baseline in HIV RNA at Week 48   [ Baseline and Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in HIV RNA at Week 48
Measure Description Mean change from baseline at Week 48 in HIV RNA (log10 copies/mL)
Time Frame Baseline and 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.
Observed mean change from baseline in log10 Plasma HIV RNA for each group was calculated using the conventional imputation (replace HIV RNA <400 copies/mL by 400 copies/mL if signal detected, or 200 copies/mL if signal not detected. Missing values: baseline-carry-forward for all failures or discontinued due to lack of efficacy

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		231 118
Change From Baseline in HIV RNA at Week 48
[units: HIV RNA (log10 copies/mL)]
Mean ( 95% Confidence Interval ) 		-1.67
( -1.81 to -1.54 )		 -0.68
( -0.86 to -0.50 )

No statistical analysis provided for Change From Baseline in HIV RNA at Week 48



4.  Secondary:   Change From Baseline in CD4 Cell Count at Week 16   [ Baseline and Week 16 ]

Measure Type Secondary
Measure Title Change From Baseline in CD4 Cell Count at Week 16
Measure Description Mean change from baseline at Week 16 in CD4 Cell Count (cells/mm^3)
Time Frame Baseline and Week 16  
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.
Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 Cell Count (cells/mm^3) was carried forward for patients who discontinued assigned therapy due to lack of efficacy.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		231 118
Change From Baseline in CD4 Cell Count at Week 16
[units: CD4 Cell Count (cells/mm^3)]
Mean ( 95% Confidence Interval ) 		82.7
( 70.5 to 94.9 )		 31.3
( 17.8 to 44.8 )

No statistical analysis provided for Change From Baseline in CD4 Cell Count at Week 16



5.  Secondary:   Change From Baseline in CD4 Cell Count at Week 48   [ Baseline and Week 48 ]

Measure Type Secondary
Measure Title Change From Baseline in CD4 Cell Count at Week 48
Measure Description Mean change from baseline at Week 48 in CD4 Cell Count (cells/mm^3)
Time Frame Baseline and 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.
Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 Cell Count (cells/mm^3) was carried forward for patients who discontinued assigned therapy due to lack of efficacy.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		230 119
Change From Baseline in CD4 Cell Count at Week 48
[units: CD4 Cell Count (cells/mm^3)]
Mean ( 95% Confidence Interval ) 		120.2
( 102.2 to 138.1 )		 49.4
( 30.4 to 68.5 )

No statistical analysis provided for Change From Baseline in CD4 Cell Count at Week 48



6.  Other Pre-specified:   Proportion of Patients Achieving HIV RNA <50 Copies/mL at Week 48   [ 48 weeks ]

Measure Type Other Pre-specified
Measure Title Proportion of Patients Achieving HIV RNA <50 Copies/mL at Week 48
Measure Description No text entered.
Time Frame 48 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.
No text entered.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. Plus OBT No text entered.
Placebo Plus OBT No text entered.

Measured Values
  Raltegravir 400 mg b.i.d. Plus OBT Placebo Plus OBT
Number of Participants Analyzed
[units: participants] 		231 118
Proportion of Patients Achieving HIV RNA <50 Copies/mL at Week 48
[units: Participants]
 		149 37

No statistical analysis provided for Proportion of Patients Achieving HIV RNA <50 Copies/mL at Week 48




  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


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.  


Results Point of Contact:  
Name/Title: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck & Co., Inc.
phone: 1-800-672-6372


Publications:
Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H; BENCHMRK Study Teams. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):339-54.
Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65.


Responsible Party: Merck & Co., Inc. ( Executive Vice President, Clinical and Quantitative Sciences )
Study ID Numbers: 2005_096, MK0518-018
Study First Received: February 14, 2006
Results First Received: August 18, 2009
Last Updated: November 12, 2009
ClinicalTrials.gov Identifier: NCT00293267     History of Changes
Health Authority: France: Ministry of Health





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