A Phase III/IV Factorial Randomized Double-blind Trial to Compare the Addition of Dapagliflozin vs Placebo and Rosuvastatin/Ezetimibe Versus Pitavastatin in Patients With HIV on Integrase Strand Transfer Inhibitor-based Antiretrovirals With Elevated Metabolic Risk
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 300
- 试验地点
- 13
- 主要终点
- To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe on low-density lipoproteins (LDL) concentration
研究概览
简要总结
People with HIV are at a higher risk of cardiovascular diseases (CVD) due to the effects of the virus and its treatment. Integrase strand transfer inhibitors (INSTIs), a common HIV treatment, are associated with increased CVD risk and metabolic issues, such as weight gain and high blood pressure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, however, have been working well in reducing CVD events and hospitalizations due to heart failure, irrespective of diabetes presence. They also help in reducing weight and blood pressure. Pitavastatin has shown to work in lowering CVD events in people with HIV, but its availability is limited. This benefit is thought to be common to all statins, but this has not yet been confirmed. This study will examine the impact of dapagliflozin vs. placebo on metabolic parameters in people with HIV with high metabolic risk who are on INSTI-based ART.
详细描述
This is a 2x2 factorial, randomised, placebo-controlled, double-blind, phase III/IV trial with two randomisations performed centrally via an on-line system, stratified by site. Participants will be randomised 1:1 to dapagliflozin 10mg vs. Placebo; this randomisation will be blinded. Participants will also be randomised 1:1 within each group to pitavastatin 4mg vs. rosuvastatin 10mg/ezetimibe 10mg; this randomisation will be open label.
Therefore, participants will be randomised to one of 4 groups:
- Dapagliflozin 10mg + pitavastatin 4mg
- Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg
- Placebo + pitavastatin 4mg
- Placebo + rosuvastatin 10mg/ezetimibe 10mg
With the following 2-arm randomised comparisons:
- Primary analysis hypothesis: a+b vs c+d (dapagliflozin vs placebo)
- Secondary analysis hypothesis: a+c vs b+d (pitavastatin vs rosuvastatin 10mg/ezetimibe 10mg)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 40-75 years and at least one of the following risk factors:
- •BMI > 7% increase or > 5kg weight gain since INSTI commencement, or
- •BMI ≥ 30 kg/m2
- •BMI ≥18 kg/m2 prior to INSTI commencement
- •Currently taking INSTI-based ART
- •Sustained virologic response, defined as viral load <200 copies/mL for at least 12 months
- •Current CD4 >250 cells/mm3
- •Informed consent for trial participation
排除标准
- •Currently taking a protease inhibitor
- •Indicated to take or already taking high intensity statin
- •estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2
- •Currently taking an SGLT-2 inhibitor or glucagon-like peptide 1 (GLP-1) agonist
- •Absolute contraindication or absolute indication to SGLT2 inhibitor therapy
- •Absolute contraindication to pitavastatin, rosuvastatin, ezetimibe or combination of rosuvastatin/ezetimibe
- •Pregnant or breast feeding
- •Severe hepatic impairment (Child Pugh B or C)
- •Participants receiving any excluded/contraindicated medication
- •Participants who are enrolled into an additional interventional study.
- •Expected inability or unwillingness to participate in study procedures.
- •In the opinion of the investigator, participation in a trial is not in the best interest of the patient.
研究组 & 干预措施
Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg
Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
干预措施: Rosuvastatin and Ezetimibe (Drug)
Placebo + rosuvastatin 10mg/ezetimibe 10mg
Placebo + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
干预措施: Rosuvastatin and Ezetimibe (Drug)
Dapagliflozin 10mg + pitavastatin 4mg
Dapagliflozin 10mg + pitavastatin 4mg given as daily tablets for 48 weeks
干预措施: Dapagliflozin 10mg Tab (Drug)
Dapagliflozin 10mg + pitavastatin 4mg
Dapagliflozin 10mg + pitavastatin 4mg given as daily tablets for 48 weeks
干预措施: Pitavastatin 4 Mg Oral Tablet (Drug)
Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg
Dapagliflozin 10mg + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
干预措施: Dapagliflozin 10mg Tab (Drug)
Placebo + pitavastatin 4mg
Placebo + pitavastatin 4mg given as daily tablets for 48 weeks
干预措施: Pitavastatin 4 Mg Oral Tablet (Drug)
Placebo + pitavastatin 4mg
Placebo + pitavastatin 4mg given as daily tablets for 48 weeks
干预措施: Placebo (Drug)
Placebo + rosuvastatin 10mg/ezetimibe 10mg
Placebo + rosuvastatin 10mg/ezetimibe 10mg given as daily tablets for 48 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe on low-density lipoproteins (LDL) concentration
时间窗: 24 weeks
Mean change in LDL as absolute change from baseline to 24 weeks across treatment arms
To assess the impact of dapagliflozin vs. placebo on weight reduction
时间窗: 24 weeks
Mean reduction change in body weight across treatment arms at 24 weeks, defined as absolute body weight change.
次要结局
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to hip (cm) ratio(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Atherosclerotic cardiovascular disease risk score (ASCVD) - calculation of a person's10-year risk (%) of having a cardiovascular problem.(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on haemoglobin A1C (%)(48 weeks)
- To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on Atherosclerotic cardiovascular disease risk score (ASCVD) - calculation of a person's10-year risk (%) of having a cardiovascular problem.(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on Serious adverse events.(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting glucose (mmol/L)(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on measures of fatty liver disease: Liver Function Tests - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (U/L), FibroScan (kPa)(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)(48 weeks)
- To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on fasting lipids including: Total Cholesterol (mmol/L), LDL (mmol/L), High-Density Lipoproteins (HDL) (mmol/L), Triglycerides (mmol/L)(48 weeks)
- To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on inflammatory biomarkers (tested centrally on stored research samples)(48 weeks)
- To assess the impact of pitavastatin vs. rosuvastatin/ezetimibe from baseline to 48 weeks on serious adverse events(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on body mass index (BMI )- weight and height will be combined to report BMI in kg/m^2(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on waist (cm) to height (cm) ratio(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on systolic and diastolic blood pressure (mm Hg)(48 weeks)
- To assess the impact of dapagliflozin vs. placebo from baseline to 48 weeks on fasting lipids including: Total Cholesterol (mmol/L), LDL (mmol/L), High-Density Lipoproteins (HDL) (mmol/L), Triglycerides (mmol/L)(48 weeks)