Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 186
- 试验地点
- 7
- 主要终点
- Efficacy of DTG-based maintenance therapy (< 100 copies/ml)
研究概览
简要总结
The purpose of this study is to evaluate whether maintenance antiretroviral therapy could be simplified to DTG + FTC dual therapy and/or patient-centered monitoring once virological suppression is achieved. Using a factorial design, the study aims to assess the efficacy of DTG + FTC dual therapy to maintain virological suppression through 48 weeks of follow-up as well as the costs of a patient-centered ART laboratory monitoring.
详细描述
This is a pragmatic multicentre, 2x2 factorial randomized controlled trial with 1:1:1:1 randomization to switching to DTG-based maintenance dual therapy in association with FTC or continuation of cART, and to patient-centered monitoring or continuation of standard monitoring.
Patients will be followed during 48 weeks.
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
- 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
- •Informed consent as documented by signature;
- •Documented HIV-1 infection;
- •Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
- •≥ 18 years of age;
- •HIV-RNA <50 copies/mL at screening and for at least 24 weeks before screening on effective suppressive cART, one blip with less than 200 copies/mL being allowed during this period if followed by at least 2 results < 50 copies/mL.
- •On standard cART at the time of inclusion, i.e.:
- •2 NRTIs + either 1 NNRTI, 1 boosted PI or 1 INSTI;
- •NRTI-sparing triple ARV regimen (e.g. 1 NRTI + 1 NNRTI + 1 InSTI);
- •Dual therapy with protease inhibitor.
排除标准
- •HIV-2 infection;
- •Previous ART change for unsatisfactory virological response, i.e. slow initial virological suppression, incomplete suppression or rebound. Change of drug or drug class for convenience or toxic effect prevention or management is allowed.
- •Note: patients with documented genotype(s) presenting only a M184V mutation remain eligible;
- •Creatinine clearance < 50ml/min;
- •ASAT or ALAT >2.5x upper limit of the norm;
- •Known hypersensitivity, intolerance or allergy to DTG or FTC;
- •Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months;
- •Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
- •Women who are pregnant or breast-feeding;
- •a. Presence of any INSTI-resistance. Non-availability of INSTI resistance testing is NOT an exclusion criteria.
- •b. Non availability of previous routine resistance test, at least for reverse transcriptase and protease genes.
- •Note: Subjects remain eligible in the absence of any previous resistance test only if they are on their first-line antiretroviral regimen;
- •Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.
研究组 & 干预措施
Continuing cART + Patient-centered monitoring
Patients randomized to this arm will continue their current cART and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
干预措施: Patient-centered monitoring (Other)
Switch to DTG+FTC + Standard monitoring
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36
干预措施: Switch to DTG + FTC (Drug)
Switch to DTG+FTC + Patient-centered monitoring
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed at screening and at week 48. In addition, patients will be ask to choose at least one of the following alternative options for weeks 6, 12 and 36: decentralised venipuncture and blood tests, delivery of ARV drugs by mail and Assessment and clinical interview by phone or skype call
干预措施: Switch to DTG + FTC (Drug)
Switch to DTG+FTC + Patient-centered monitoring
Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed at screening and at week 48. In addition, patients will be ask to choose at least one of the following alternative options for weeks 6, 12 and 36: decentralised venipuncture and blood tests, delivery of ARV drugs by mail and Assessment and clinical interview by phone or skype call
干预措施: Patient-centered monitoring (Other)
结局指标
主要结局
Efficacy of DTG-based maintenance therapy (< 100 copies/ml)
时间窗: 48 weeks
Proportion of patients maintaining HIV-RNA \<100 copies/ml throughout 48 weeks
Costs of a patient-centered ART monitoring
时间窗: 48 weeks
Direct costs of the two study arms from the health care system perspective at week 48
次要结局
- Global satisfaction of the monitoring(48 weeks)
- Change in HIV-DNA(48 weeks)
- ARV treatment in the post study(48 weeks)
- Efficacy of DTG-based maintenance therapy (<50 copies/ml)(48 weeks)
- Change in CD4 cell count(48 weeks)
- PROQOL questionnaire(48 weeks)
- HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)(48 weeks)
- Proportion of patients with a severe adverse event(48 weeks)
- Change in glucose profile(48 weeks)
- Proportion of patients with CNS adverse event(48 weeks)
- Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis(48 weeks)
- Change in glomerular function rate(48 weeks)
- Proportion of patients new to DTG with CNS symptoms(6 weeks)
- Patient's monitoring satisfaction for pts in the patient-centered monitoring arm(48 weeks)
- Change in lipidic profile(48 weeks)
- Change in Framingham-calculated cardiovascular risk(48 weeks)
- Proportion of patients with an adverse event(48 weeks)
- Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options(48 weeks)
- Patient's treatment satisfaction at week 48(48 weeks)
- Study satisfaction(48 weeks)
- Cost-effectiveness of study arms(48 weeks)
- Change in patient weight(48 weeks)
- Number of study-related extra clinical visits(48 weeks)
- Adherence questions(48 weeks)
研究者
Calmy Alexandra
Professor
University Hospital, Geneva