- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01423812
DRIVESHAFT: Darunavir/Ritonavir In HIV-infected Virologically-suppressed Experienced Subjects (DRIVESHAFT)
DRIVESHAFT: Phase IV Randomized, Open-Label Study in HIV-1 Virologically-suppressed Patients On Regimens With Darunavir 600mg/Ritonavir 100mg Twice-daily Switching to Darunavir 800mg/Ritonavir 100mg Once-daily Vs. Continuing Twice-daily Darunavir/Ritonavir Regimens
Study Overview
Status
Conditions
Detailed Description
The Darunavir/Ritonavir In Virologically-suppressed Experienced Subjects Halving an Antiretroviral by Finetuning Therapy (DRIVESHAFT) study was a prospective, randomized, single-centre, two-arm, open-label 48-week pilot study. The aim of DRIVESHAFT was to evaluate the safety and efficacy of switching the DRV/r component from twice-daily to once-daily 800/100 mg compared with those remaining on current therapy among HIV-1-infected, treatment-experienced patients with 0-1 DRV RAMs on a stable regimen including twice-daily DRV/r 600/100 mg. The study was conducted at The Ruth M Rothstein CORE Center (Chicago, IL, USA). The sample size was determined upon feasibility as a single-site study and not powered for non-inferiority. Study enrolment was planned for 60 participants randomized 1:1 to one of two arms: the switch arm from DRV/r 600/100 mg twice daily to DRV/r 800/100 mg once/daily plus current ARV regimen including a minimum of two other agents or remain on current ARV regimen with minimum of three agents inclusive of twice-daily DRV/r. Two DRV 400 mg tablets were used in the once-daily DRV/r arm, with DRV 600 mg tablets administered in the twice-daily DRV/r arm.
DRIVESHAFT inclusion criteria included HIV-1-infected adult (>18 years of age), HIV-1 RNA measurements <40 copies/ml (using a local assay) over at least 12 weeks on a stable regimen including DRV/r 600/100 mg twice daily plus a minimum of two other ARVs, screening HIV-1 RNA<40 copies/ml, have undergone genotypic testing at any time prior to starting current antiretroviral therapy (ART) with evidence of <2 cumulative DRV RAMs, CD4+ T-cell count >50 cells/mm3, and a negative serum pregnancy test at screening visit Participants who were randomized and received at least one dose of study medication were included in efficacy analysis, and the primary end point was the proportion of participants with HIV-1 RNA<40 copies/ml at week 48.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Illinois
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Chicago, Illinois, United States, 60612
- Ruth M. Rothstein CORE Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- ART-experienced, HIV-1 infected subjects ≥18 years of age.
A female subject is eligible to enter and participate in the study if she:
- is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or,
is of child-bearing potential, with a negative pregnancy test at both Screen and Day 1 and agrees to one of the following methods of contraception to avoid pregnancy:
- Complete abstinence from intercourse from 2 weeks prior to administration of study medications, throughout the study, and for at least 2 weeks after discontinuation of all study medications.
- Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide).
- Approved hormonal contraception may be administered with darunavir/ritonavir
- Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year
- Any other method with published data showing that the expected failure rate is <1% per year.
Any contraception method must be used consistently and in accordance with the approved product label. All subjects participating in the study should be counseled on safer sexual practices including the use of effective barrier methods (e.g. male condom/spermicide).
- CD4 >50 cells/mm3
- HIV-1 RNA concentrations at undetectable levels (according to local assay being used) for at least 12 weeks on stable current regimen
- Current regimen includes darunavir/ritonavir 600/100 mg twice-daily plus a minimum of two other antiretrovirals
- Negative serum pregnancy test at screening visit
Exclusion Criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
- Known hypersensitivity reaction to agents being utilized in the study
- >1 cumulative darunavir associated mutations (V11I, V32I, L33F, I47V, I50V, I54L or M, T74P, L76V, I84V, or L89V) detected from any previous genotype or a VircoTYPE HIV-1 darunavir fold-change >10.0 on any previous virtual phenotype
- Pregnant or breast feeding woman
- Liver dysfunction with Child-Pugh class C disease or decompensated cirrhosis
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Once-daily Darunavir and ritonavir
Subjects switched from Darunavir 600mg plus Ritonavir 100mg twice-daily to Darunavir 800mg plus Ritonavir 100mg once-daily
|
Subjects randomized 1:1 to switch to from combination Darunavir 600mg plus Ritonavir 100mg twice-daily at baseline to the experimental combination Darunavir 800mg plus Ritonavir 100mg once-daily for 48 weeks
Other Names:
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Active Comparator: Twice-daily Darunavir and ritonavir
Subjects remain on regimens containing Darunavir 600mg plus Ritonavir 100mg twice-daily
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Subjects randomized 1:1 to remain on regimens containing combination Darunavir 600mg plus Ritonavir 100mg twice-daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Primary Efficacy Endpoint for Virologic Suppression in HIV-infected Subjects
Time Frame: 48 weeks after randomization to study medication
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Proportion of subjects with plasma HIV-1 RNA <40 c/mL at Week 48 using a Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA's "snapshot" algorithm
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48 weeks after randomization to study medication
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Assessment of Virologic Failure
Time Frame: Within 48 weeks of randomization to study medications
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•Assess the development of viral resistance in subjects experiencing virological failure
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Within 48 weeks of randomization to study medications
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Secondary Efficacy Endpoints
Time Frame: Within 24 weeks after randomization to study medication
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•Proportion of subjects with plasma HIV-1 RNA >200 c/mL at Week 24
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Within 24 weeks after randomization to study medication
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Change in Total Cholesterol From Baseline to 48 Weeks
Time Frame: Within 48 weeks of randomization baseline to study medications
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Absolute change in lipid parameter (total cholesterol mg/dl) of once-daily versus twice-daily darunavir/ritonavir containing regimens over 48 weeks
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Within 48 weeks of randomization baseline to study medications
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Absolute Value Change in CD4+ From Baseline to Week 48
Time Frame: 48 weeks after randomization baseline to study medications
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Absolute value increase in CD4+ cells/mm3 from baseline to week 48
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48 weeks after randomization baseline to study medications
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Number of Participants With Greater Than 95% Adherence at 48 Weeks
Time Frame: Within 48 weeks of randomization to study medications
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Characterize adherence to once-daily versus twice-daily darunavir/ritonavir containing regimens using the Modified Medication Adherence Self-Report Inventory (M-MASRI) scale
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Within 48 weeks of randomization to study medications
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Secondary Efficacy Endpoints
Time Frame: week 24
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•Proportion of subjects with plasma HIV-1 RNA <40 c/mL at Week 24
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week 24
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: GREGORY G HUHN, MD, The Ruth M. Rothstein CORE Center
Publications and helpful links
General Publications
- Huhn GD, Sigman A, Livak B. Simplification from twice-daily to once-daily darunavir/ritonavir in a randomized trial among HIV-infected persons with HIV-1 RNA suppression on antiretroviral therapy. Antivir Ther. 2015;20(8):849-54. doi: 10.3851/IMP2962. Epub 2015 Apr 17.
- Molto J, Valle M, Santos JR, Mothe B, Miranda C, Cedeno S, Negredo E, Yritia M, Videla S, Barbanoj MJ, Clotet B. 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. doi: 10.3851/IMP1519.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Ritonavir
- Darunavir
Other Study ID Numbers
- TMC114HIV4063
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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