Reducing Systemic Inflammation in People on Antiretroviral Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in total uncalcified plaque volume between baseline and month 24
研究概览
简要总结
This randomized, open-label clinical trial will evaluate whether adding fostemsavir to current antiretroviral therapy can reduce the risk of cardiovascular disease in people with well-controlled HIV. Researchers will compare imaging, clinical and biomarker outcomes between participants who receive fostemsavir in addition to their existing treatment and those who continue with standard care alone.
详细描述
A randomized, controlled trial of fostemsavir versus standard of care to curb comorbidity in people with well-controlled HIV. (Phase IIb study)
Background and hypothesis: People living with HIV, even when treated with antiretrovirals, develop early onset comorbidities such as cardiovascular disease, cognitive decline and frailty. In a subset of those, this could be due to residual viral particles driving chronic inflammation. Soluble glycoprotein 120 (sgp120) is detectable in close to a third of people living with HIV with undetectable HIV plasma viral loads. It is associated to increased inflammation and immune dysfunction.
People living with HIV with undetectable viral load but detectable soluble HIV gp120 (sgp120) are exposed to chronic inflammation, sustained immune dysfunction, and increased risk of comorbidity. The investigators hypothesize that the addition of fostemsavir, which has been shown to prevents the binding of sgp120 to the human CD4 receptor, to reduce cytokine burst and antibody-dependant cellular citotoxicity, decreased inflammation and immune dysfunction, leading to improved health.
Study population: People living with HIV on antiretroviral therapy, with undetectable viral load and detectable plasmatic sgp120.
Study intervention: The intervention will be either the addition of fostemsavir (Rukobia 600 mg daily) for 24 months to the patient's current ART regimen, or standard of care, which includes the continuation of the ARV regimen and other medications prescribed by their physicians.
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
- Single (Outcomes Assessor)
盲法说明
This trial will be conducted as an open-label study; however, assessors of the primary outcome (based on two CCTA scans) and of the biobank analyses will remain blinded to treatment allocation, as well as statisticians.
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
- •40 years or older, or have lived with HIV for 25 years or more, any sex;
- •Undetectable HIV viral load (defined as last viral load measurement less than 50 copies/ml within the last 6 months);
- •Presence of at least one cardiovascular risk factor among the following: longstanding HIV infection (25 years or more), hypertension, diabetes, past or present smoking, dyslipidemia, family history of early onset CVD in a first-degree relative (defined as younger than 55 in males or younger than 65 in females (80)), known previous cardiovascular disease (defined as past myocardial infarction, coronary revascularization, stroke, or coronary artery atherosclerosis with >= 50% stenosis demonstrated on coronary angiography or CCTA);
- •Participants with past cardiovascular disease must be in a stable clinical condition as judged by the study clinicians;
- •Past cardiovascular events are defined as having occurred at least 3 months before screening;
- •Evidence of detectable plasmatic sgp120 levels at any point in the past year, using the assay described priorly and performed at CRCHUM in Dr Andrés Finzi's laboratory.
排除标准
- •Known allergy to study drug;
- •Concomitant treatment with strong cytochrome P450 (CYP3A) inducers, including but not limited to: carbamazepine, phenytoin (anticonvulsants), mitotane (antineoplastic), enzalutamide (androgen receptor inhibitor), rifampicin (antimycobacterial) and St John's wort (Hypericum perforatum, herbal supplement);
- •Planning to become pregnant, pregnant, or breastfeeding (as requested per product monography (55)). Females of childbearing potential must have a negative pregnancy test at baseline visit, and follow contraception requirements throughout the treatment;
- •Contraindication for CT scan use (estimated glomerular filtration rate [eGFR] less than 40ml/min using the Modification of Diet in Renal Diseases [MDRD] formula or iodine allergy);
- •Elevated risk of prior ionizing radiation exposure outside clinical care exceeding 10 mSV over 3 years, per the investigator's judgement (eg. a participant with occupational ionizing radiation exposure, prior participation in clinical trials with multiple CT scans)
- •Confirmed uncorrected QT value >500ms or confirmed QTcF >470 msec for women and >450 msec for men;
- •Acquired/ congenital long QT syndrome;
- •Current or anticipated treatment with any of the following medications: amiodarone, disopyramide, dofetilide, ibutilide, procainamide, sotalol, and quinidine;
- •Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy (INR > 2.0), hypoalbuminemia (<30 mg/ml), untreated esophageal or gastric varices, or persistently elevated bilirubinemia (>1.5x upper limit of normal [ULN]), known biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment);
- •ALT >=5 times the ULN, OR ALT >=3xULN and bilirubin >=1.5xULN with >35% direct bilirubin;
- •History of liver cirrhosis with CHILD-PUGH classification C;
- •Inability to provide informed consent;
- •Life expectancy of less than 36 months;
- •Inability to present to study visits;
- •Participation in another interventional trial;
- •Known Congestive heart failure with NYHA class 3 or 4.
研究组 & 干预措施
Rukobia 600 mg daily
干预措施: Fostemsavir (Drug)
结局指标
主要结局
Change in total uncalcified plaque volume between baseline and month 24
时间窗: From baseline to end of treatment (+ 24 months)
The change in total uncalcified plaque volume between baseline and month 24 will be measured by coronary compted tomography angiography and contrasted between fostemsavir and standard of care
次要结局
- Imaging outcome: Perivascular fat attenuation index at month 24, adjusted for baseline values(From baseline to end of treatment (+ 24 months))
- Time to Major Adverse cardiovascular Event (MACE)(From baseline to post-treatment visit (+ 27 months))
- Risk of severe and serious adverse events(From baseline to post-treatment visit (+ 27 months))
- Grip strength at 24 months, adjusted for baseline(From baseline to end of treatment (+ 24 months))
- Brief Cognitive Ability Measure (B-CAM) scores at month 24, adjusted for baseline(From baseline to end of treatment (+ 24 months))