Prospective, Randomised, Crossover, Double-Blind, Placebo-Controlled Trial To Assess The Lipid-Lowering Effect Of Adding Tenofovir/Emtricitabine Co-Formulation Vs Placebo To Hiv-1-Infected Subjects With Dyslipidemia And Sustained Viral Load Suppression Under Monotherapy With Ritonavir-Boosted Protease Inhibitors
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- LDL-cholesterol
研究概览
简要总结
This is a phase IV, multicenter, prospective, randomised, crossover, double blind, placebo-controlled and proof of concept clinical trial.
All subjects fulfilling inclusion criteria will be randomised to add either TDF/FTC co-formulation (group A) or placebo (Group B) to their current PI/r regimen, i.e.: DRV/r 800/100 mg QD or LPV/r 400/100 BID. This will be followed by a crossover addition of TDF/FTC co-formulation or placebo.
Randomization will be centralised in the CRO FLS-Research Support and will be stratified by DRV/r or LPV/r intake at baseline to ensure equal distribution in both arms. TDF/FTC co-formulation or Placebo will be provided in a double-blinded fashion, i.e.: neither the treating physician nor the patient will know whether the patient is receiving TDF/FTC or placebo.
All subjects will receive dietary counselling to promote lipid-lowering diet provided by a specialised dietician throughout the study.
The expected duration of the study for each participant will be 36 weeks. There will be 6 visits: screening, baseline and weeks 4, 12, 24 and 36.
详细描述
This is a phase IV, multicenter,, prospective, randomised, crossover, double blind, placebo-controlled and proof of concept clinical trial. The trial was conducted in a total sample of 60 patients (30 patients per group), which assures adequate power to detect differences. This study is adequate to demonstrate the lipid-lowering effect of TDF/FTC co-formulation addition in patients with dyslipidemia and stable monotherapy antiretroviral treatment.
All subjects fulfilling inclusion criteria will be randomised to add either TDF/FTC co-formulation (group A) or placebo (Group B) to their current PI/r regimen, i.e.: DRV/r 800/100 mg QD or LPV/r 400/100 BID. This will be followed by a crossover addition of TDF/FTC co-formulation or placebo.
In Group A the expected changes in cholesterol values, regarding baseline, can be observed 3 months after TDF/FTC addition. After this, a period of 3 months with placebo will act as a washout period, allowing establishing comparisons intra-patient. Finally, another period of 3 months with placebo will permit to establish comparisons with the first 3-month TDF/FTC intervention. In Group B, subjects will follow a 3-month placebo period, later a 3-month TDF/FTC intervention and finally a placebo period that will act as a wash-out.
Randomization will be centralised in the CRO FLS-Research Support and will be stratified by DRV/r or LPV/r intake at baseline to ensure equal distribution in both arms. TDF/FTC co-formulation or Placebo will be provided in a double-blinded fashion, i.e.: neither the treating physician nor the patient will know whether the patient is receiving TDF/FTC or placebo.
All subjects will receive dietary counselling to promote lipid-lowering diet provided by a specialised dietician throughout the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- •Age ≥ 18 years
- •Chronic HIV-1 infection
- •Antiretroviral treatment with either DRV/r (800/100 mg QD) or LPV/r (400/100 mg BID) monotherapy during at least 6 months prior to screening.
- •Fasting total cholesterol or LDL-cholesterol levels ≥ 200 and ≥130 mg/dL respectively, in the previous two consecutive tests obtained at least 4 weeks apart before screening.
- •Calculated creatinine clearance ≥ 60 mL/min, according to the Cockcroft-Gault formula.
- •Undetectable plasma HIV-1 RNA levels (< 50 copies/mL) during at least 6 months prior to screening.
- •Adequate treatment adherence.
- •Absence of TDF or FTC resistances.
- •Written informed consent to participate into the study.
排除标准
- •Acute infections or uncontrolled chronic infection in the 2 months previous to the inclusion or physical examination that, in the investigator's opinion, would compromise the patient's safety or outcome of the study
- •Lactating, pregnancy or fertile women willing to be pregnant.
- •Concomitant use of any drug with potential drug-drug interaction with DRV/r, LPV/r or TDF/FTC co-formulation at study entry.
- •Concomitant use of any lipid-lowering drugs at study entry.
- •Prior documented intolerance or hypersensitivity to TDF, FTC, LPV/r or DRV/r.
- •Therapies including interferon, interleukin-2, cytotoxic chemotherapy or immunosuppressors at study entry.
- •Acute or chronic renal documented pathologies.
- •Documented resistance to any of the study drugs (either genotypic or phenotypic)
- •Life expectancy less or equal to 1 year.
- •Current alcohol or substance use judged by the investigator to potentially interfere with subject study compliance.
- •Subjects currently taking part in any other clinical trial using an investigational product, with the exception of studies where the treatment studied have stopped for more than 12 weeks.
- •Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements.
研究组 & 干预措施
TDF/FTC (3 months) + Placebo (6 months)
TDF/FTC (3 months) + Placebo (6 months)
干预措施: Truvada® (300 mg tenofovir disoproxil fumarato/200 mg emtricitabine) (Drug)
Placebo (3 months) + TDF/FTC (3 months) + Placebo (3 months)
Placebo (3 months) + TDF/FTC (3 months) + Placebo (3 months)
干预措施: Placebo (Drug)
结局指标
主要结局
LDL-cholesterol
时间窗: Baseline, week 4, 12, 24 and 36
Total fasting cholesterol
时间窗: Baseline, week 4, 12, 24 and 36
次要结局
- CD4 cell count(Baseline, week 4, 12, 24 and 36)
- Changes in liver enzymes(Baseline, week 4, 12, 24 and 36)
- Changes in phosphate(Baseline, week 4, 12, 24 and 36)
- Changes in creatinine(Baseline, week 4, 12, 24 and 36)
- Changes in glomerular filtration rate(Baseline, week 4, 12, 24 and 36)
- Changes in HDL cholesterol(Baseline, week 4, 12, 24 and 36)
- Changes in triglycerides(Baseline, week 4, 12, 24 and 36)
- Adverse events(Baseline, week 4, 12, 24 and 36)
- Resistance mutations(Baseline, week 4, 12, 24 and 36)
- lipid-lowering drugs(Baseline, week 4, 12, 24 and 36)