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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 11
- 主要终点
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
- •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
研究组 & 干预措施
Raltegravir plus Nevirapine plus Lamivudine
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
干预措施: Raltegravir (MK-0518) (Drug)
Raltegravir plus Nevirapine plus Lamivudine
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
干预措施: Nevirapine (Drug)
Raltegravir plus Nevirapine plus Lamivudine
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
干预措施: Lamivudine (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Tenofovir (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Emtricitabine (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Lopinavir (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Ritonavir (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Atazanavir (Drug)
Protease Inhibitor/Ritonavir plus tenofovir/emtricitabine
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
干预措施: Darunavir (Drug)
结局指标
主要结局
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR)
时间窗: 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.
次要结局
- Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 Ribonucleic Acid [RNA]) at Week 48(Week 48)
- Change From Baseline of HIV-RNA Absolute Values(Baseline and Week 96)
- Percentage of Participants With Altered Values of Tubular Kidney Injury Markers.(Up to Week 96)
- Percentage of Participants With Suppressed Viremia (<50 Copies/mL HIV-1 RNA) at Week 96(Week 96)
- Percentage of Participants With Decline in Renal Function at Week 48(Week 48)
- Percentage of Participants With Virologic Failure (HIV-1 RNA > 50 Copies/mL)(Up to Week 96)
- Percentage of Participants With Altered Liver Enzymes and Lipid Profile(Up to Week 96)
- Percentage of Participants Having Changes From Baseline in Metabolic Bone Markers(Baseline and up to Week 96)
- Percentage of Participants With Adherence to Study Therapy(Up to Week 96)
- Change From Baseline in the VACS Index(Baseline and week 96)
- Change From Baseline in eGFR at Week 96(Baseline and Week 96)
- Percentage of Participants With Mutations Associated With Resistance to NRTIs, NNRTIs, INI, at Virological Failure.(Up to Week 96)
- Change From Baseline in Absolute CD4+ T-lymphocyte Count(Baseline and Week 96)
- Area Under the Concentration Time Curve From Time 0 the Last Measurement Time t (AUC0-t) for Raltegravir and Nevirapine(Week 12: Fasted state (0 h) and 1, 2, 3, 6 and 12 h post-dose)
- Trough Concentration (Ctrough) for Raltegravir and Nevirapine(Weeks 12 and 48: at the end of dosing interval at 12 h)
- Percentage of Participants With Genotypic Resistance at Virologic Failure.(Up to Week 96)
- Change From Baseline in Bone Disease Risk Assessment(Baseline and week 96)
- Percentage of Participants Experiencing a Decline of Renal Function(Up to Week 96)