HIV InfectionsPhase 2RANIANCT02116660
Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284)
A Phase 2 study testing Raltegravir (MK-0518), Nevirapine and Lamivudine in people with HIV Infections, run by Merck Sharp & Dohme LLC.
Trial summary
To evaluate changes in renal function, efficacy, and safety when switching from a combination of tenofovir/emtricitabine (TDF/FTC) plus a protease inhibitor/ritonavir (PI/r) to a combination of raltegravir (MK-0518) plus nevirapine plus lamivudine in human immunodeficiency virus (HIV)-1 infected participants with… 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 (MK-0518), Nevirapine and Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- No sites listed yet
- Study dates
- 3 Sep 2014to 10 Jul 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male, or non-pregnant, non-breastfeeding female
- No previous history of virological failure
- No previous exposure to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors
- No previous history of intolerance to lamivudine
- At least 2 documented plasma HIV-1 RNA <50 copies/mL and no HIV-1 >50 copies/mL in the 12 months before screening
- Receiving the same protease inhibitor/ritonavir plus tenofovir/emtricitabine combination for at least the 6 months before screening
- Has no major International Antiviral Society (IAS)-USA mutations on genotype testing performed before starting antiretroviral treatment
- Sexually-active participants and their partners of child-bearing potential agree to use a medically acceptable method of contraception from 2 weeks before Day 1 and for at least 6 months after the last dose of study drug (postmenopausal women are not required to use contraception; sexually-active male participants with a female partner of child-bearing potential must provide written informed consent to information regarding any pregnancy)
Who cannot join
- Positive for hepatitis B surface antigen (HBsAg+) or anticipated need for hepatitis C virus treatment
- Liver cirrhosis
- Has a history of diabetes mellitus, defined as initiation of antidiabetic treatment or verification of diabetes in a case report form
- Has any cancer, excluding stable Kaposi Sarcoma
- Allergy or sensitivity to the investigational product or excipients
- Female participant who is nursing
Show all 10Show fewer
- Female participant who is pregnant or intends to become pregnant
- Has an active Acquired Immunodeficiency Syndrome (AIDS)-defining event except stable Kaposi Sarcoma or HIV Wasting Syndrome
- Received any investigational drug within 30 days before screening
- Participated in any other clinical trial within 30 days before signing informed consent for the current trial
About this study
Official title: Switching From Regimens Consisting of a RTV-Boosted Protease Inhibitor Plus TDF/FTC to a Combination of Raltegravir Plus Nevirapine and Lamivudine in HIV Patients With Suppressed Viremia and Impaired Renal Function (RANIA Study) (Pilot Study) Protocol MK-0518-284-03
To evaluate changes in renal function, efficacy, and safety when switching from a combination of tenofovir/emtricitabine (TDF/FTC) plus a protease inhibitor/ritonavir (PI/r) to a combination of raltegravir (MK-0518) plus nevirapine plus lamivudine in human immunodeficiency virus (HIV)-1 infected participants with suppressed viremia and impaired renal function.
- Conditions
- HIV Infections
- Being tested
- Raltegravir (MK-0518), Nevirapine, Lamivudine, Tenofovir, Emtricitabine
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raltegravir (MK-0518)Drug
Raltegravir (MK-0518) 400 mg tablets
NevirapineDrug
Nevirapine (NVP) 200 mg tablets
LamivudineDrug
Lamivudine (3TC) 150 mg tablets
TenofovirDrug
Tenofovir disoproxil fumarate (TDF) 300 mg tablets
EmtricitabineDrug
Emtricitabine (FTC) 200 mg tablets
LopinavirDrug
Lopinavir (LPV) 200 mg tablets
RitonavirDrug
Ritonavir (r) 100 mg tablets
AtazanavirDrug
Atazanavir (ATV) 300 mg tablets
DarunavirDrug
Darunavir (DAR) 400 mg tablets
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir plus Nevirapine plus Lamivudine | Experimental | Raltegravir 400 mg oral twice daily for 96 weeks; plus nevirapine 200 mg oral once daily for 14 days followed by nevirapine 200 mg oral twice daily, plus lamivudine 150 mg oral twice daily for 96 weeks Receives: Drug: Raltegravir (MK-0518); Drug: Nevirapine; Drug: Lamivudine |
| Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine | Active comparator | Tenofovir/emtricitabine 300/200 mg oral once daily plus 1) lopinavir/ritonavir 400/100 mg oral twice daily or 800/200 mg oral once daily, or 2) atazanavir/ritonavir 300/100 mg oral once daily, or 3) darunavir/ritonavir 800/100 mg oral once daily or 600/100 mg oral twice daily Receives: Drug: Tenofovir; Drug: Emtricitabine; Drug: Lopinavir; Drug: Ritonavir; Drug: Atazanavir; Drug: Darunavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.
Measured: Baseline and Week 48
Secondary outcomes (18)
Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48
Plasma was to be collected at Week 48 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.
Measured: Week 48
Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96
Plasma was to be collected at Week 96 in order to quantify HIV-1 RNA. and identify the percentage of participants with <50 copies/mL HIV-1 RNA.
Measured: Week 96
Percentage of Participants With Decline in Renal Function at Week 48
Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.
Measured: Week 48
Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)
Plasma was to be collected up to Week 96 in order to quantify HIV-1 RNA, and identify the percentage of participants with >50 copies/mL HIV-1 RNA.
Measured: Up to Week 96
Change From Baseline of HIV-RNA Absolute Values
Plasma was to be collected at baseline and Week 96 in order to determine the change from baseline in HIV-1 RNA.
Measured: Baseline and Week 96
Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure.
Participants were to be identified with mutations associated with Nucleoside/ Nucleotide Reverse Transcriptase Inhibitors (NRTIs), Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), and Integrase Inhibitor (INI). Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.
Measured: Up to Week 96
Change From Baseline in Absolute CD4+ T-lymphocyte Count
Cluster of Differentiation 4 + (CD4+) T-lymphocyte cell counts were to be determined at baseline and Week 96, in order to determine the change from baseline.
Measured: Baseline and Week 96
Percentage of Participants With Altered Liver Enzymes and Lipid Profile
Values of liver enzymes and lipids were to be determined from laboratory tests, in order to identify the percentage of participants classified with altered values.
Measured: Up to Week 96
Percentage of Participants With Altered Values of Tubular Kidney Injury Markers.
Values of tubular kidney injury markers. were to be determined, in order to identify the percentage of participants classified with altered values.
Measured: Up to Week 96
Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers
Changes from baseline in metabolic bone markers, serum Bone Specific Alkaline Phosphatase (s-BSAP) and C-telopeptides of type 1 Collagen (s-CTx), were to be determined, in order to classify the percentage of participants with changes.
Measured: Baseline and up to Week 96
Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine
Blood samples were to be collected in Week 12 in order to use the trapezoidal method to determine the AUC0-t of Raltegravir and Nevirapine
Measured: Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose
Trough Concentration (Ctrough) for Raltegravir and Nevirapine
Blood samples were to be collected in Weeks 12 and 48 in order to use the trapezoidal method to determine the Ctrough, the lowest concentration reached by the drug before the next dose is administered, of Raltegravir and Nevirapine.
Measured: Weeks 12 and 48: at the end of dosing interval at 12 h
Percentage of Participants With Genotypic Resistance at Virologic Failure.
Genotypic resistance measures the presence of particular HIV-1 mutations that give rise to drug resistance. Virological failure is defined as 2 consecutive plasma HIV-1 RNA >200 copies/mL at least two weeks apart while on previous or current ARV therapy.
Measured: Up to Week 96
Percentage of Participants With Adherence to Study Therapy
An Adherence Questionnaire was to be given in order to determine the percentage of participants who adhered to study therapy.
Measured: Up to Week 96
Change From Baseline in Bone Disease Risk Assessment
Bone disease risk assessment was to be based on a Fracture Risk Assessment Tool (FRAX®) score in participants > 40 years old, and the change from baseline determined.
Measured: Baseline and week 96
Change From Baseline in the VACS Index
The Veterans Aging Cohort Risk Index (VACS Index) combines various clinical biomarkers into a cumulative index weighted according to the risk of all-cause mortality.
Measured: Baseline and week 96
Percentage of Participants Experiencing a Decline of Renal Function
Decline in renal function was to be assessed by evaluating MDRD-6, creatinine clearance and serum phosphate.
Measured: Up to Week 96
Change From Baseline in eGFR at Week 96
Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.
Measured: Baseline and Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2014 (estimated)
- Study start3 Sep 2014
- Primary completion10 Jul 2017
- Study completion10 Jul 2017
Why it stopped: This study was terminated early due to poor recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02116660
- Sponsor's protocol ID
- 0518-284
- Other IDs
- 2013-001637-40, MK-0518-284
- Acronym
- RANIA
- Status last verified
- Apr 2019
- First submitted
- 15 Apr 2014
- Last updated
- 8 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching From Regimens Consisting of a RTV-Boosted Protease Inhibitor Plus TDF/FTC to a Combination of Raltegravir Plus Nevirapine and Lamivudine in HIV Patients With Suppressed Viremia and Impaired Renal Function (RANIA Study) (Pilot Study) Protocol MK-0518-284-03
- ClinicalTrials.gov ID
- NCT02116660
- Acronym / sponsor ID
- RANIA / 0518-284
- Conditions
- HIV Infections
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated early due to poor recruitment.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 3 Sep 2014 (actual)
- Primary completion
- 10 Jul 2017 (actual)
- Study completion
- 10 Jul 2017 (actual)
- First posted
- 17 Apr 2014 (estimated)
- Results
- Posted 8 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate changes in renal function, efficacy, and safety when switching from a combination of tenofovir/emtricitabine (TDF/FTC) plus a protease inhibitor/ritonavir (PI/r) to a combination of raltegravir (MK-0518) plus nevirapine plus lamivudine in human immunodeficiency virus (HIV)-1 infected participants with suppressed viremia and impaired renal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Raltegravir plus Nevirapine plus Lamivudine | Experimental | Drug: Raltegravir (MK-0518), Drug: Nevirapine, Drug: LamivudineRaltegravir 400 mg oral twice daily for 96 weeks; plus nevirapine 200 mg oral once daily for 14 days followed by nevirapine 200 mg oral twice daily, plus lamivudine 150 mg oral twice daily for 96 weeks |
| Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine | Active comparator | Drug: Tenofovir, Drug: Emtricitabine, Drug: Lopinavir, Drug: Ritonavir, Drug: Atazanavir, Drug: DarunavirTenofovir/emtricitabine 300/200 mg oral once daily plus 1) lopinavir/ritonavir 400/100 mg oral twice daily or 800/200 mg oral once daily, or 2) atazanavir/ritonavir 300/100 mg oral once daily, or 3) darunavir/ritonavir 800/100 mg oral once daily or 600/100 mg oral twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male, or non-pregnant, non-breastfeeding female
- No previous history of virological failure
- No previous exposure to non-nucleoside reverse transcriptase inhibitors or integrase inhibitors
- No previous history of intolerance to lamivudine
- At least 2 documented plasma HIV-1 RNA <50 copies/mL and no HIV-1 >50 copies/mL in the 12 months before screening
Key exclusion criteria (10 listed)
- Positive for hepatitis B surface antigen (HBsAg+) or anticipated need for hepatitis C virus treatment
- Liver cirrhosis
- Has a history of diabetes mellitus, defined as initiation of antidiabetic treatment or verification of diabetes in a case report form
- Has any cancer, excluding stable Kaposi Sarcoma
- Allergy or sensitivity to the investigational product or excipients
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 |
|---|---|---|
| Raltegravir (MK-0518)Raltegravir (MK-0518) 400 mg tablets | Drug | Raltegravir plus Nevirapine plus Lamivudine |
| NevirapineNevirapine (NVP) 200 mg tablets | Drug | Raltegravir plus Nevirapine plus Lamivudine |
| LamivudineLamivudine (3TC) 150 mg tablets | Drug | Raltegravir plus Nevirapine plus Lamivudine |
| TenofovirTenofovir disoproxil fumarate (TDF) 300 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
| EmtricitabineEmtricitabine (FTC) 200 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
| LopinavirLopinavir (LPV) 200 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
| RitonavirRitonavir (r) 100 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
| AtazanavirAtazanavir (ATV) 300 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
| DarunavirDarunavir (DAR) 400 mg tablets | Drug | Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine |
Primary outcome
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline and Week 48
Glomerular Filtration Rate (eGFR) was estimated from the Modification of Diet in Renal Disease (MDRD)-6 equation. The MDRD-6 equation = 198 × [serum creatinine(mg/dL)]^-0.858 × [age]-0.167 × [0.822 if patient is female] × [1.178 if patient is black] × [serum urea nitrogen concentration (mg/dL)]^-0.293 × [urine urea nitrogen excretion (g/d)]^0.249.
18 secondary outcomes
Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48
Time frame: Week 48
Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96
Time frame: Week 96
Percentage of Participants With Decline in Renal Function at Week 48
Time frame: Week 48
Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)
Time frame: Up to Week 96
Change From Baseline of HIV-RNA Absolute Values
Time frame: Baseline and Week 96
Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure.
Time frame: Up to Week 96
Change From Baseline in Absolute CD4+ T-lymphocyte Count
Time frame: Baseline and Week 96
Percentage of Participants With Altered Liver Enzymes and Lipid Profile
Time frame: Up to Week 96
Percentage of Participants With Altered Values of Tubular Kidney Injury Markers.
Time frame: Up to Week 96
Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers
Time frame: Baseline and up to Week 96
Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine
Time frame: Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose
Trough Concentration (Ctrough) for Raltegravir and Nevirapine
Time frame: Weeks 12 and 48: at the end of dosing interval at 12 h
Percentage of Participants With Genotypic Resistance at Virologic Failure.
Time frame: Up to Week 96
Percentage of Participants With Adherence to Study Therapy
Time frame: Up to Week 96
Change From Baseline in Bone Disease Risk Assessment
Time frame: Baseline and week 96
Change From Baseline in the VACS Index
Time frame: Baseline and week 96
Percentage of Participants Experiencing a Decline of Renal Function
Time frame: Up to Week 96
Change From Baseline in eGFR at Week 96
Time frame: Baseline and Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
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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.
Medical Director study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Raltegravir (MK-0518), Nevirapine and Lamivudine in people with HIV Infections, run by Merck Sharp & Dohme LLC.
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 8 inclusion and 10 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: stopped early, as of the sponsor's last update on 8 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (time frame: Baseline and Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Apr 2019.