Raltegravir And Darunavir Antiretroviral in Antiretroviral Naive Patients (RADAR)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2012 by Dallas VA Medical Center.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Roger Bedimo, M.D., Dallas VA Medical Center
ClinicalTrials.gov Identifier:
NCT00677300
First received: May 8, 2008
Last updated: August 31, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to determine whether a combination of raltegravir and darunavir is as effective as standard regimens in the treatment of HIV-infected patients who have not previously used antiretroviral drug (treatment naive)


Condition Intervention Phase
HIV Infections
Drug: Raltegravir
Drug: Darunavir
Drug: Ritonavir
Drug: Tenofovir/Emtricitabine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Evaluation of Safety and Efficacy of Raltegravir/Darunavir Combination in Antiretroviral-Naive Patients

Resource links provided by NLM:


Further study details as provided by Dallas VA Medical Center:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Median change in CD4 count from baseline [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with treatment-emergent fasting hypertriglyceridemia (TG >400) or hypercholesterolemia (TC >240) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Median change in limb fat from baseline, by DEXA scan [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Changes from baseline in insulin resistance measured by homeostasis model assessment (HOMA-IR) [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 80
Study Start Date: January 2009
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A
Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily)
Drug: Raltegravir
400mg P.O. (orally) twice daily for 48 weeks
Other Name: Isentris
Drug: Darunavir
800 mg P.O. (orally) once daily
Other Name: Prezista
Drug: Ritonavir
100mg once daily
Other Name: Norvir
Active Comparator: Group B
Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily)
Drug: Darunavir
800 mg P.O. (orally) once daily
Other Name: Prezista
Drug: Ritonavir
100mg once daily
Other Name: Norvir
Drug: Tenofovir/Emtricitabine
300 mg/200 mg P.O. (orally) once daily
Other Name: Truvada

  Hide Detailed Description

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:

  1. Group A: will receive Raltegravir + Ritonavir-boosted Darunavir
  2. Group B: will receive Tenofovir + Emtricitabine + Ritonavir-boosted Darunavir
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00677300

Locations
United States, Texas
Dallas VA Medical Center
Dallas, Texas, United States, 75216
Parkland Health & Hospital System
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Dallas VA Medical Center
Merck Sharp & Dohme Corp.
Tibotec Pharmaceutical Limited
Investigators
Principal Investigator: Roger Bedimo, M.D. Dallas VA Medical Center
  More Information

No publications provided

Responsible Party: Roger Bedimo, M.D., ID Section Chief, Dallas VA Medical Center
ClinicalTrials.gov Identifier: NCT00677300     History of Changes
Other Study ID Numbers: Merck 072-00
Study First Received: May 8, 2008
Last Updated: August 31, 2012
Health Authority: United States: Federal Government

Keywords provided by Dallas VA Medical Center:
HIV
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Darunavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on August 27, 2014