A Phase IV, Open-label, Multi Centre Pilot Study to Assess Changes in Cerebral Function Parameters in Patients Without Perceived Central Nervous System (CNS) Symptoms When Switched From a Fixed Dose Combination of Tenofovir/Emtricitabine/Efavirenz (Atripla®) to a Fixed Dose Combination of Tenofovir/Emtricitabine/Rilpivirine (Eviplera®)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 3
- 主要终点
- Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the change in sleep score using the Pittsburgh Sleep Questionnaire.
研究概览
简要总结
This study aims to investigate whether substitution of Efavirenz (EFV) as the Tenofovir/Emtricitabine/Efavirenz (TDF/FTC/EFV) fixed-dose combination (FDC) Atripla, with Rilpivirine as the tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) fixed-dose combination (FDC) Eviplera, leads to resolution of covert Central Nervous System (CNS) toxicity associated with EFV, continued virological suppression and immunological reconstitution and whether this is associated with an improvement in quality of life, sleep, anxiety/depression and neurocognitive function; the impact of switch on adherence will also be investigated.
详细描述
Protocol Summary
Study Title: SSAT 058 - A phase IV, open-label, multi centre pilot study to assess the prevalence of objective neurocognitive abnormality in patients without perceived Central Nervous System (CNS) symptoms on tenofovir/emtricitabine/efavirenz Atripla® and the effect of switching to a fixed dose combination of tenofovir/emtricitabine/rilpivirine (Eviplera®).
Proposed Sponsor: St Stephen's AIDS Trust
Chief Investigator: Dr Mark Nelson
Name of Investigational Product: Eviplera®
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patient volunteers who meet all of the following criteria are eligible for this trial:
- •Is male or female aged 18 years or above
- •Has HIV-1 infection documented in their medical notes
- •Has signed the Informed Consent Form voluntarily
- •Is willing to comply with the protocol requirements
- •Has been on Atripla for at least 12 weeks before enrolment
- •Has an undetectable HIV-plasma viral load at screening by local assay (single re-test allowed)
- •Has a CD4 cell count at screening >50 cells/mm3
- •Has an estimated glomerular filtration rate (MDRD) >50 ml/min.
- •Has no significant CNS symptoms which may be attributable to EFV.
- •If female and of childbearing potential, is using effective birth control methods (for example, hormonal contraceptive, condom, abstinence, IUD, as agreed by the investigator) and is willing to continue practising these birth control methods during the trial and for at least 30 days after the end of the trial. Note: Women who are postmenopausal for least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of non-childbearing potential
- •If a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit
排除标准
- •Patients meeting 1 or more of the following criteria cannot be selected:
- •Infected with HIV-2
- •Using any concomitant therapy disallowed as per SPC for the study drugs (e.g proton pump inhibitors )
- •Has acute viral hepatitis including, but not limited to, A, B, or C
- •Has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Patients can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period.
- •Any investigational drug within 30 days prior to the trial drug administration
- •Has ever received rilpivirine in the past
- •Any clinical evidence of baseline resistance mutations, prior to commencing antiretroviral therapy.
- •Known allergy to lactose monohydrate, sunset yellow aluminium lake (E110), and patients with galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
- •Severe hepatic impairment (defined as Child-Pugh-Turcotte (CPT) Score C).
- •If female, she is pregnant or breastfeeding
- •Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).
- •Any condition (including drug/alcohol abuse) or laboratory results which, in the investigator's opinion, interfere with assessments or completion of the trial.
- •If participating in the MR Imaging substudy, any contraindications to magnetic resonance scanning according to local radiology guidelines (to be assessed by MR Spectroscopy Imaging Department)
研究组 & 干预措施
Switch from Atripla to Eviplera
干预措施: Eviplera (Drug)
结局指标
主要结局
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the change in sleep score using the Pittsburgh Sleep Questionnaire.
时间窗: 4 Weeks compared to baseline
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity
时间窗: 4 Weeks compared to baseline
As defined by the ACTG Adverse event scale and collected by CNS questionnaire.
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity
时间窗: 4 Weeks compared to baseline
As defined by the ACTG adverse event scale and collected by CNS questionnaire.
Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 4 weeks compared to baseline, as measured by the median CNS score.
时间窗: 4 Weeks compared to baseline
Derived from the sum of toxicity of all grades collected in the CNS questionnaire.
次要结局
- Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median number of grade 2-4 neuropsychiatric and CNS toxicity.(12 and 24 weeks compared to baseline)
- Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by change in sleep score using the Pittsburgh Sleep Questionnaire.(12 and 24 weeks compared to baseline)
- Change in mean fasting cholesterol (total, HDL, LDL and total:HDL ratio) and triglycerides after 4, 12 and 24 weeks compared with baseline.(4, 12 and 24 weeks compared to baseline)
- Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 and 24 weeks compared to baseline, as measured by the median CNS score(12 and 24 weeks compared to baseline)
- Change in neuropsychiatric and central nervous system (CNS) parameters after switching from Atripla to TDF/FTC/RPV at 12 & 24 weeks compared to baseline, as measured by proportion of patients experiencing grade 2-4 neuropsychiatric and CNS toxicity.(12 and 24 weeks compared to baseline)
- Change in neuropsychiatric and CNS parameters as measured by the change in the Hospital Anxiety and Depression Scale (HADS) at 4, 12 and 24 weeks as compared with baseline.(4, 12 and 24 weeks compared to baseline)
- Proportion of patients with undetectable viral load (by local assay) at weeks 4, 12 and 24.(4, 12 and 24 weeks compared to baseline)
- Proportion of patients with viral load below 400 copies/mL at weeks 4, 12 and 24.(4, 12 and 24 weeks compared to baseline)
- Change in CD4+ count at week 12 and 24 compared to baseline.(12 and 24 weeks compared to baseline)
- Proportion of patients with grade 2-4 laboratory adverse events (excluding lipids) and proportion of patients with grade 2-4 non-CNS adverse events at 4, 12 and 24 weeks compared with baseline.(4, 12 and 24 weeks compared to baseline)
- Change in cerebral MR-measurable imaging modalities at 24 weeks compared with baseline.(24 weeks compared to baseline)
- Change in adherence as measured by the adherence questionnaire: Medication Adherence Self-Report Inventory (M-MASRI) at 12 and 24 weeks compared with baseline.(12 and 24 weeks compared to baseline)
- Change in quality of life (as assessed by EQ-5D questionnaire) at 4, 12 and 24 weeks compared with baseline.(4, 12 and 24 weeks compared to baseline)
- Change in neurocognitive function as determined by computerised neurocognitive assessment (no computerised cognitive testing at week 12)(4, 12 and 24 weeks compared to baseline)
- Change in neurocognitive function as determined by Instrumental Activities of Daily Life (IADL) questionnaire(4, 12 and 24 weeks compared to baseline)