MULTICENTRE STUDY TO ASSESS CHANGES IN BONE MINERAL DENSITY OF THE SWITCH FROM PROTEASE INHIBITORS TO DOLUTEGRAVIR IN HIV-1-INFECTED SUBJECTS WITH LOW BONE MINERAL DENSITY
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 75
- 试验地点
- 3
- 主要终点
- Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry
研究概览
简要总结
Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.
Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
详细描述
The second generation integrase inhibitor dolutegravir has demonstrated good virological and immunological outcomes in antiretroviral-naive subjects, compared with efavirenz, (SPRING 1 study). As well, it is active against HIV strains resistant to first-generation inhibitors raltegravir and elvitegravir in heavily treatment-experienced patients (VIKING study).
Additionally, it was safe and well tolerated after two years of use. It is administered once daily with no need for boosting, no food requirements and has a long half-life. The easy posology and its pharmacokinetics, together with the antiviral potency, make this drug a good alternative as a simplification approach. However, no clinical data are available supporting the switch of protease inhibitors or no nucleoside reverse transcriptase inhibitors to dolutegravir in virologically suppressed HIV-treated subjects.
Protease inhibitors (PI) have been associated with an acceleration of bone mineral density loss in HIV-infected individuals because of an enhanced osteoclast activity, although some controversial data have been also published. A first study suggest an increase of bone mineral density after switching from PI to raltegravir, the first generation integrase inhibitor, but there are no more data about this subject.
Based on data that PI decrease bone mineral density by accelerating osteoclast cells and that the discontinuation of this drugs could improve bone mineralization, we propose a randomized prospective multicenter study to assess the impact of switching from PI to dolutegravir on bone mineral density in patients with low bone mineral density receiving a PI-containing regimen. At the same time, the study will help to assess the antiviral efficacy and safety of a PI-sparing regimen including dolutegravir as a simplification strategy in virologically suppressed patients.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-infected patients over 18 years.
- •In current antiretroviral therapy with abacavir and lamivudine (Kivexa) plus ritonavir-boosted PI, at least 6 months.
- •Viral suppression (HIV RNA <50 copies / ml) for at least 12 months.
- •T-score ≤ -1 evaluated by DEXA (done in the last 6 months).
- •Signed informed consent.
- •In potential childbearing women, commitment to use barrier contraceptive method throughout the study.
排除标准
- •Suspected or documented resistance to integrase inhibitors or reverse transcriptase inhibitors, nucleoside analogues.
- •Osteoporosis / osteopenia secondary (testosterone deficiency, thyroid disease ...), except vitamin D deficiency
- •Treatment with bisphosphonates in the last 6 months.
- •Have used integrase inhibitors
- •Pregnant or breastfeeding.
- •Patients with alanine aminotransferase (ALT)> 5 times the upper limit of normal (ULN) or ALT ≥ 3 times ULN and bilirubin ≥ 1.5 times ULN (direct bilirubin> 35%)
- •Patients with severe hepatic dysfunction (Class B or C) according to the Child-Pugh classification
- •Patients infected with hepatitis B virus (HBV) who can not use entecavir or telbivudine.
- •Patients infected with hepatitis C virus (HCV) in which is expected to begin treatment during the study.
研究组 & 干预措施
Dolutegravir 50mg
Dolutegravir 50mg every 24 hours + Kivexa (ABC+3TC)
干预措施: Dolutegravir, 50mg every 24 hours (Drug)
Protease Inhibitor/ritonavir
Protease Inhibitor/ritonavir + Kivexa (ABC+3TC)
干预措施: Protease Inhibitor/ritonavir (Drug)
结局指标
主要结局
Compare changes in Bone Mineral Density (BMO) measured by Dual-energy X-ray absorptiometry
时间窗: From Baseline to week 48
Compare changes in femur T-score measured by DEXA
时间窗: From Baseline to week 48
Compare changes in lumbar spine (L1-L4) T-score measured by DEXA
时间窗: From Baseline to week 48
次要结局
- HIV-1 viral load(week 48)
- Compare changes in proteinuria/creatinine ratio(at week 48 relative to baseline values)
- Adverse events related to antiretroviral treatment (Toxicity).(From Baseline to week 48)
- Patient withdrawal(From Baseline to week 48)
- Compare changes in osteocalcin(at week 48 relative to baseline values)
- Compare changes in alkaline phosphatase(at week 48 relative to baseline values)
- CD4+/CD8+ T lymphocytes count.(week 48)
- Genotypic test if virological failure occurs.(From baseline to week 48)
- Compare changes in total cholesterol(at week 48 relative to baseline values)
- Compare changes in HDL cholesterol(at week 48 relative to baseline values)
- Compare changes in LDL cholesterol(at week 48 relative to baseline values)
- Compare changes in triglyceride levels.(at week 48 relative to baseline values)
- Compare changes in filtrate glomerular rate by MDRD equation(at week 48 relative to baseline values)
- Compare changes in creatinine(at week 48 relative to baseline values)
- Compare changes in albumine/creatinine ratio(at week 48 relative to baseline values)
- Compare changes in telopeptide(at week 48 relative to baseline values)