HIV InfectionsPhase 4RADARNCT00677300
Raltegravir And Darunavir Antiretroviral in Antiretroviral Naive Patients
A Phase 4 study testing Raltegravir, Darunavir and Ritonavir in people with HIV Infections, run by Dallas VA Medical Center at 2 sites in United States.
Trial summary
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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Raltegravir, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2009to Dec 2012
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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):
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dallas VA Medical Center
Dallas, Texas, 75216
Parkland Health & Hospital System
Dallas, Texas, 75390
About this study
Official title: Evaluation of Safety and Efficacy of Raltegravir/Darunavir Combination in Antiretroviral-Naive Patients
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)
Read the 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
- Conditions
- HIV Infections
- Being tested
- Raltegravir, Darunavir, Ritonavir, Tenofovir/Emtricitabine
- Keywords
- HIV, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RaltegravirDrug
Also called Isentris
400mg P.O. (orally) twice daily for 48 weeks
DarunavirDrug
Also called Prezista
800 mg P.O. (orally) once daily
RitonavirDrug
Also called Norvir
100mg once daily
Tenofovir/EmtricitabineDrug
Also called Truvada
300 mg/200 mg P.O. (orally) once daily
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Will receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Receives: Drug: Raltegravir; Drug: Darunavir; Drug: Ritonavir |
| Group B | Active comparator | Will receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Tenofovir/Emtricitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: Week 24
Secondary outcomes (4)
Median change in CD4 count from baseline
Measured: 48 Weeks
Percentage of patients with treatment-emergent fasting hypertriglyceridemia (TG >400) or hypercholesterolemia (TC >240)
Measured: 48 weeks
Median change in limb fat from baseline, by DEXA scan
Measured: 48 weeks
Changes from baseline in insulin resistance measured by homeostasis model assessment (HOMA-IR)
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2008 (estimated)
- Study startJan 2009
- Primary completionOct 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dallas VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Merck Sharp & Dohme LLC, Tibotec Pharmaceutical Limited
- Responsible party
- Principal investigator, Roger Bedimo, M.D., Dallas VA Medical Center
- Investigators
- Roger Bedimo, M.D., Principal investigator, Dallas VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00677300
- Sponsor's protocol ID
- Merck 072-00
- Acronym
- RADAR
- Status last verified
- Sep 2014
- First submitted
- 8 May 2008
- Last updated
- 8 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Bedimo RJ, Drechsler H, Jain M, Cutrell J, Zhang S, Li X, Farukhi I, Castanon R, Tebas P, Maalouf NM. The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health. PLoS One. 2014 Aug 29;9(8):e106221. doi: 10.1371/journal.pone.0106221. eCollection 2014.
PubMed 25170938
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Safety and Efficacy of Raltegravir/Darunavir Combination in Antiretroviral-Naive Patients
- ClinicalTrials.gov ID
- NCT00677300
- Acronym / sponsor ID
- RADAR / Merck 072-00
- Conditions
- HIV Infections
- Keywords
- HIV, Treatment Naive
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Dallas VA Medical CenterUS federal agency
- Collaborators
- Merck Sharp & Dohme LLC, Tibotec Pharmaceutical Limited
- Study start
- Jan 2009
- Primary completion
- Oct 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 14 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Raltegravir, Drug: Darunavir, Drug: RitonavirWill receive Raltegravir (400mg twice daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) |
| Group B | Active comparator | Drug: Darunavir, Drug: Ritonavir, Drug: Tenofovir/EmtricitabineWill receive Tenofovir (300mg once daily) + Emtricitabine (200mg once daily) + Ritonavir-boosted (100mg once daily) Darunavir (800mg once daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RaltegravirAlso: Isentris400mg P.O. (orally) twice daily for 48 weeks | Drug | Group A |
| DarunavirAlso: Prezista800 mg P.O. (orally) once daily | Drug | Group A, Group B |
| RitonavirAlso: Norvir100mg once daily | Drug | Group A, Group B |
| Tenofovir/EmtricitabineAlso: Truvada300 mg/200 mg P.O. (orally) once daily | Drug | Group B |
Primary outcome
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
4 secondary outcomes
Median change in CD4 count from baseline
Time frame: 48 Weeks
Percentage of patients with treatment-emergent fasting hypertriglyceridemia (TG >400) or hypercholesterolemia (TC >240)
Time frame: 48 weeks
Median change in limb fat from baseline, by DEXA scan
Time frame: 48 weeks
Changes from baseline in insulin resistance measured by homeostasis model assessment (HOMA-IR)
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2014.
- Derived from this study: PubMed 25170938Bedimo RJ, Drechsler H, Jain M, Cutrell J, Zhang S, Li X, Farukhi I, Castanon R, Tebas P, Maalouf NM. The RADAR study: week 48 safety and efficacy of RAltegravir combined with boosted DARunavir compared to tenofovir/emtricitabine combined with boosted darunavir in antiretroviral-naive patients. Impact on bone health. PLoS One. 2014 Aug 29;9(8):e106221. doi: 10.1371/journal.pone.0106221. eCollection 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roger Bedimo, M.D. principal investigator
Dallas VA Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Raltegravir, Darunavir and Ritonavir in people with HIV Infections, run by Dallas VA Medical Center at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00677300, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2014.