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DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects (DRIVESHAFT)

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ClinicalTrials.gov Identifier: NCT01423812
Recruitment Status : Completed
First Posted : August 26, 2011
Results First Posted : February 7, 2018
Last Update Posted : February 7, 2018
Sponsor:
Collaborator:
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Information provided by (Responsible Party):
Gregory Huhn, Ruth M. Rothstein CORE Center

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition HIV
Interventions Drug: Twice-daily Darunavir and ritonavir
Drug: Once-daily Darunavir and ritonavir
Enrollment 60
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Hide Arm/Group Description

Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily

Once-daily Darunavir/ritonavir: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks

Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Twice-daily Darunavir/ritonavir: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Period Title: Overall Study
Started 30 30
Completed 27 26
Not Completed 3 4
Reason Not Completed
Lost to Follow-up             2             2
Withdrawal by Subject             1             2
Arm/Group Title Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir Total
Hide Arm/Group Description

Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily

Once-daily Darunavir/ritonavir: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks

Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Twice-daily Darunavir/ritonavir: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Total of all reporting groups
Overall Number of Baseline Participants 30 30 60
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
30
 100.0%
29
  96.7%
59
  98.3%
>=65 years
0
   0.0%
1
   3.3%
1
   1.7%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants 30 participants 60 participants
48
(36 to 65)
49
(38 to 66)
48
(36 to 66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 30 participants 60 participants
Female
6
  20.0%
5
  16.7%
11
  18.3%
Male
24
  80.0%
25
  83.3%
49
  81.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants 30 participants 60 participants
30 30 60
1.Primary Outcome
Title Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects
Hide Description Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 48 using a Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA's "snapshot" algorithm
Time Frame 48 weeks after randomization to study medication
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Hide Arm/Group Description:

Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily

Once-daily Darunavir/ritonavir: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks

Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Twice-daily Darunavir/ritonavir: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Overall Number of Participants Analyzed 30 30
Measure Type: Number
Unit of Measure: participants
27 25
2.Secondary Outcome
Title Secondary Efficacy Endpoints
Hide Description
  • Proportion of subjects with plasma HIV-1 RNA <50 c/mL and <400 c/mL at Week 24
  • Proportion of subjects with plasma HIV-1 RNA <400 c/mL at Week 48
Time Frame Within 48 weeks after randomization to study medication
Outcome Measure Data Not Reported
3.Secondary Outcome
Title Safety Assessment
Hide Description •Compare the tolerability, safety, and change in lipid parameters(total cholesterol, LDL, HDL, triglycerides) of once-daily versus twice-daily darunavir/ritonavir containing regimens over 48 weeks
Time Frame Within 48 weeks of randomization to study medications
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Immunologic Endpoints
Hide Description •Absolute values and changes from baseline in CD4+ and CD8+ over time
Time Frame 48 weeks after randomization to study medications
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Assessment of Virologic Failure
Hide Description •Assess the development of viral resistance in subjects experiencing virological failure
Time Frame Within 48 weeks of randomization to study medications
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Medication Adherence Assessment
Hide Description Characterize adherence to once-daily versus twice-daily darunavir/ritonavir containing regimens using the Modified Medication Adherence Self-Report Inventory (M-MASRI) scale
Time Frame Within 48 weeks of randomization to study medications
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Secondary Efficacy Endpoints
Hide Description •Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24
Time Frame week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Once-daily Darunavir and Ritonavir Twice-daily Darunavir and Ritonavir
Hide Arm/Group Description:

Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily

Once-daily Darunavir and ritonavir: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks

Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Twice-daily Darunavir and ritonavir: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Overall Number of Participants Analyzed 30 30
Measure Type: Count of Participants
Unit of Measure: Participants
29
  96.7%
25
  83.3%
Time Frame 48 weeks during the trial, and 30 days after participant completion of the trial
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Hide Arm/Group Description

Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily

Once-daily Darunavir/ritonavir: Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks

Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

Twice-daily Darunavir/ritonavir: Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily

All-Cause Mortality
Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Once-daily Darunavir/Ritonavir Twice-daily Darunavir/Ritonavir
Affected / at Risk (%) Affected / at Risk (%)
Total   0/30 (0.00%)   0/30 (0.00%) 
The sample size was not adequately powered to evaluate non-inferiority, which might be clinically relevant. As a single-center study, identifying an appropriate number of eligible patients to determine non-inferiority was not feasible.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Gregory Huhn, MD
Organization: The Ruth M. Rothstein CORE Center
Phone: 312-572-4575
Publications:
1. De Meyer S, et al. Antiviral activity of TMC 114, a potent next generation protease inhibitor against more than 4000 recent recombinant clinical isolates exhibiting a wide range of protease inhibitor resistance profile. Antiviral Ther 2003;8:3S19. 2. De Meyer S, et al. In vitro selection experiments demonstrate an increased genetic barrier to resistance development to TMC 114 as compared with currently licensed protease inhibitors. Antiviral Ther 2002;7(Suppl 1):S5. 3. De Meyer SD, et al. Phenotypic and genotypic determinants of resistance to TMC 114: pooled analysis of POWER 1,2, and 3. Antiviral Ther 2006;11:S83. 4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. December 1,2009;1-161. Available at http://www.aidsinfo.nih.gov/ContentFiles/Adultand AdolescentGL.pdf. Accessed September 15, 2010. 5. Clotet B, et al. Efficacy and Safety of Darunavir/ritonavir at week 48 in treatment-experienced patients with HIV-1 infection in POWER 1 and 2: A Pooled Subgroup Analysis of Data from Two Randomized Trials. The Lancet 2007;369:1169-78. 6. Cahn PK, et al. Efficacy and Safety at 48 Weeks of Once-daily vs Twice-daily DRV.r in Treatment-experienced HIV-1-positive Patients with No DRV Resistance-associated Mutations: The ODIN Trial. Abstract 57. 17th Conference on Retroviruses and Opportunistic Infections (CROI 2010). San Francisco. February 16-19, 2010. 7. Moltó J, et al. Treatment simplification to once daily darunavir/ritonavir guided by the darunavir inhibitory quotient in heavily pretreated HIV-infected patients. Antivir Ther. 2010;15(2):219-25. 8. Paterson DL, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000;133:21-30.
Responsible Party: Gregory Huhn, Ruth M. Rothstein CORE Center
ClinicalTrials.gov Identifier: NCT01423812     History of Changes
Other Study ID Numbers: TMC114HIV4063
First Submitted: August 24, 2011
First Posted: August 26, 2011
Results First Submitted: September 15, 2015
Results First Posted: February 7, 2018
Last Update Posted: February 7, 2018