- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00677300
Raltegravir And Darunavir Antiretroviral in Antiretroviral Naive Patients (RADAR)
Evaluation of Safety and Efficacy of Raltegravir/Darunavir Combination in Antiretroviral-Naive Patients
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
STUDY RATIONALE:
The current guidelines for HIV treatment in antiretroviral naive patients recommend the use of two drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class in addition to one drug in the protease inhibitor (PI) or in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class.
NRTI use is associated with significant toxicity, including mitochondrial dysfunction (mostly attributed to thymidine-analogue NRTIs): lipoatrophy, peripheral neuropathy, pancreatitis, lactic acidosis. There's also a significant risk of hypersensitivity reaction from Abacavir, and caution is needed when using Tenofovir in patients with renal failure.
Finding effective NRTI-free regimens would have a number of potential benefits including: 1) a significant expansion of therapeutic options; despite the growing number of antiretrovirals, treatment options might still be significantly limited in a patient with a number of baseline NRTI mutations or poor NRTI tolerance; 2) potential avoidance of toxicities.
Raltegravir is a leading candidate in a new class of antiretroviral medications called integrase inhibitors. It is currently approved for use in antiretroviral treatment experienced patients, but has been shown to have excellent virologic efficacy in naïve as well as heavily treatment experienced patients. It also has been shown to have unusually rapid virologic response. This profile might be excellent in delaying emergence of viral resistance in naïve patients.
Three phase III trials of Raltegravir in treatment experienced patients have been conducted (BENCHMRK trials). In both of these studies, more than 75 percent of patients receiving Raltegravir plus optimized background therapy (OBT) achieved viral load (HIV RNA) reductions to less than 400 copies/mL compared to more than 40 percent of patients receiving placebo plus OBT. Both studies also showed that Raltegravir plus OBT was generally well tolerated.
Darunavir is currently approved for use in HAART-experienced patients at the dose of 600 mg bid with ritonavir boosting. In subgroup analysis of the BENCHMRK trials, use of Raltegravir and Darunavir was associated with 90% virologic responses (HIV RNA < 400 copies/mL) at 24 weeks in treatment experienced subjects. Also, the recently presented ARTEMIS study found once-daily Darunavir to be non-inferior to either once- or twice-daily lopinavir/ritonavir in antiretroviral naïve patients. After 48 weeks a time-to-loss-of-virologic response analysis determined that 84% assigned to darunavir and 78% assigned to lopinavir had a viral load below 50 copies. In subgroup analysis, DRV/r QD was superior to LPV/r (overall) in patients with baseline viral load ≥100,000 copies/mL Furthermore, the DRV/r QD group experienced a lower incidence of lipid abnormalities than the lopinavir/ritonavir group.
HYPOTHESES
We hypothesize that the virologic efficacy (time to loss of virologic response) at 48 weeks will be at least as high following a regimen of Raltegravir + boosted Darunavir as with a regimen of Tenofovir + Emtricitabine + boosted Darunavir.
We further hypothesize that a regimen of Raltegravir + boosted Darunavir will not result in higher rates of adverse events at 48 weeks than a regimen of Tenofovir + Emtricitabine + boosted Darunavir.
STUDY DESIGN AND DURATION
This is a randomized, active Control, safety/efficacy study. All eligible patients (antiretroviral naïve,) will be randomized (1:1) into two treatment groups:
- Group A: will receive Raltegravir + Ritonavir-boosted Darunavir
- Group B: will receive Tenofovir + Emtricitabine + Ritonavir-boosted Darunavir
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Texas
-
Dallas, Texas, United States, 75216
- Dallas VA Medical Center
-
Dallas, Texas, United States, 75390
- Parkland Health & Hospital System
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- The patient has documented HIV-1 infection.
- The patient is at least 18 years of age.
- Antiretroviral naive, defined as 7 days or less of ARV treatment at any time prior to study entry. HIV viral load greater than 5,000 copies/ml within 90 days of study entry
- Willing to use acceptable forms of contraception
- Parent or guardian willing to provide informed consent, if applicable
- Hepatitis B surface antigen (HBsAg) negative at study entry
Exclusion Criteria
- Patient is current participant in a Raltegravir trial or in trials involving any of the other study medications (Darunavir, Tenofovir or Emtricitabine).
- Immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Individuals receiving either stable physiologic glucocorticoid doses, corticosteroids for acute therapy for pneumocystis pneumonia, or a short course (2 weeks or less) of pharmacologic glucocorticoid therapy will not be excluded.
- Known allergy/sensitivity to study drugs or their formulations
- Patient has a condition (including but not limited to active alcohol or drug use) that, in the opinion of the investigator, may interfere with patient adherence or safety
- Patient with acute hepatitis due to any cause or clinically significant chronic liver disease including but not limited to cirrhosis, ascites, encephalopathy, hypoalbuminemia, prolonged PT/PTT and/or esophageal varices.
- Patient has severe renal insufficiency defined as a calculated creatinine clearance at time of screening <30 mL/min, base on Cockcroft/Gault equation which is as follows (and 0.85 X this value for females):
- CrCl (mL/min) = [(140-Age) x Weight (in Kg)]/72 x Serum Creatinine (mg/mL)
- Serious illness requiring systemic treatment or hospitalization. Patients who have completed therapy or are clinically stable on therapy for at least 7 days prior to study entry are not excluded.
- Known clinically relevant cardiac conduction system disease
- Patient requires or is anticipated to require any of the prohibited medications noted in the protocol
- Current imprisonment or involuntary incarceration for psychiatric or physical (e.g., infectious disease) illness
- Pregnancy and Breastfeeding. Women who become pregnant during the study will be required to permanently discontinue their study regimens.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Group A
Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily)
|
400mg P.O.
(orally) twice daily for 48 weeks
Other Names:
800 mg P.O.
(orally) once daily
Other Names:
100mg once daily
Other Names:
|
ACTIVE_COMPARATOR: Group B
Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily)
|
800 mg P.O.
(orally) once daily
Other Names:
100mg once daily
Other Names:
300 mg/200 mg P.O.
(orally) once daily
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Time from randomization to virologic failure (HIV viral load of 1,000 copies/ml or greater at or after Week 16 and before Week 24, or two consecutive HIV viral load of 50 copies/ml or greater at or after Week 24)
Time Frame: Week 24
|
Week 24
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Median change in CD4 count from baseline
Time Frame: 48 Weeks
|
48 Weeks
|
Percentage of patients with treatment-emergent fasting hypertriglyceridemia (TG >400) or hypercholesterolemia (TC >240)
Time Frame: 48 weeks
|
48 weeks
|
Median change in limb fat from baseline, by DEXA scan
Time Frame: 48 weeks
|
48 weeks
|
Changes from baseline in insulin resistance measured by homeostasis model assessment (HOMA-IR)
Time Frame: 48 weeks
|
48 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Roger Bedimo, M.D., Dallas VA Medical Center
Publications and 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 (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- HIV Infections
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Reverse Transcriptase Inhibitors
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 Enzyme Inhibitors
- HIV Integrase Inhibitors
- Integrase Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Tenofovir
- Emtricitabine
- Raltegravir Potassium
- Ritonavir
- Darunavir
Other Study ID Numbers
- Merck 072-00
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.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
-
Florida International UniversityCompleted
-
Boston Children's HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Completed
Clinical Trials on Raltegravir
-
National Institute of Allergy and Infectious Diseases...Eunice Kennedy Shriver National Institute of Child Health and Human Development...CompletedHIV InfectionsUnited States, Puerto Rico, South Africa, Argentina, Brazil, Botswana
-
Massachusetts General HospitalMerck Sharp & Dohme LLCCompletedHIV | Neurotoxicity | HIV-associated Neurocognitive DisorderUnited States
-
ViiV HealthcareCompletedInfection, Human Immunodeficiency VirusUnited States
-
Merck Sharp & Dohme LLCCompleted
-
ViiV HealthcareGlaxoSmithKline; ShionogiCompletedHIV Infections | Infection, Human Immunodeficiency VirusUnited States, France, Netherlands, Spain, Taiwan, Australia, Belgium, Russian Federation, Canada, United Kingdom, Mexico, Italy, South Africa, Romania, Argentina, Hungary, Poland, Chile, Greece, Brazil
-
ANRS, Emerging Infectious DiseasesCompletedHIV-1 Infection | PREGNANCYFrance
-
ViiV HealthcareGlaxoSmithKline; ShionogiCompletedInfection, Human Immunodeficiency Virus IGermany, Spain, France, Australia, United States, Canada, United Kingdom, Italy, Russian Federation
-
IrsiCaixaCompleted