A Randomised Trial of Dolutegravir (DTG)-Based Antiretroviral Therapy vs. Standard of Care (SOC) in Children With HIV Infection Starting First-line or Switching to Second-line ART
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 792
- 试验地点
- 27
- 主要终点
- Difference in Proportion With Failure (Clinical or Virological)
研究概览
简要总结
A new anti-HIV medicine (Dolutegravir) combined with 2 currently used anti-HIV medicines is non-inferior to the standard combination of medicines used in terms of efficacy and better in terms of toxicity.
详细描述
The ODYSSEY study was an international randomised trial evaluating dolutegravir based antiretroviral therapy (ART) versus standard of care in HIV-infected children aged less than 18 years who were starting first line treatment (ODYSSEY A) or switching to second line treatment (ODYSSEY B). Participants had visits 4 weeks and 12 weeks after randomisation and every 12 weeks subsequent of that. They were followed up for a minimum of 96 weeks. The primary objective of the study was to assess the difference in virological or clinical failure by 96 weeks between children receiving a DTG-based regimen and those on standard of care.
At the end of study visit for the randomised phase, children and carers were invited to consent to extended follow-up. Children's visit schedules and care were as per local clinic guidelines. Participants were followed up until July 2023 in this phase of the trial. The objectives of the extended follow-up were two-fold: 1. to provide safety data for ViiV Healthcare for participants who, in the opinion of the treating physician, continue to derive benefit from dolutegravir and receive dolutegravir from ViiV Healthcare where it was not available through their country's national HIV treatment programme; 2. to monitor long-term safety and effectiveness of dolutegravir versus standard of care.
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
- None
入排标准
- 年龄范围
- 28 Days 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ALL PATIENTS:
- •Children ≥28 days and <18 years weighing ≥3kg with confirmed HIV-1 infection
- •Parents/carers and children, where applicable, give informed written consent
- •Girls aged 12 years or older who have reached menses must have a negative pregnancy test at screening and be willing to adhere to effective methods of contraception if sexually active
- •Children with co-infections who need to start ART can be enrolled into ODYSSEY according to local/national guidelines
- •Parents/carers and children, where applicable, willing to adhere to a minimum of 96 weeks' follow-up
- •Children weighing 3 to <14kg must be eligible and willing to participate in the Weight band (WB)-Pharmacokinetics (PK)1 substudy unless direct enrolment for the child's weight band has opened following the WB-PK1 substudy and/or dosing information has become available from the IMPAACT P1093 DTG dose-finding study.
- •ADDITIONAL CRITERIA FOR ODYSSEY A:
- •Planning to start first-line ART
- •ADDITIONAL CRITERIA FOR ODYSSEY B:
- •Planning to start second-line ART defined as either: (i) switch of at least 2 ART drugs due to treatment failure; or (ii) switch of only the third agent due to treatment failure where drug sensitivity tests show no mutations conferring Nucleoside Reverse Transcriptase Inhibitor (NRTI) resistance
- •Treated with only one previous ART regimen. Single drug substitutions for toxicity, simplification, changes in national guidelines or drug availability are allowed
- •At least one NRTI with predicted preserved activity available for a background regimen
- •In settings where resistance tests are routinely available, at least one new active NRTI from tenofovir disoproxil fumarate, abacavir or zidovudine should have preserved activity based on cumulative results of resistance tests
- •In settings where resistance tests are not routinely available, children who are due to switch according to national guidelines should have at least one new NRTI predicted to be available from tenofovir disoproxil fumarate, abacavir or zidovudine
- •Viral load ≥ 500 c/ml at screening visit
排除标准
- •History or presence of known allergy or contraindications to dolutegravir
- •History or presence of known allergy or contraindications to proposed available NRTI backbone or proposed available SOC third agent.
- •Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal, OR ALT ≥3x upper limit of normal and bilirubin ≥2x upper limit of normal
- •Patients with severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Anticipated need for Hepatitis C virus (HCV) therapy during the study
- •Pregnancy or breastfeeding
- •Evidence of lack of susceptibility to integrase inhibitors or more than a 2-week exposure to antiretrovirals of this class
研究组 & 干预措施
DTG arm
DTG + 2 nucleoside transcriptase inhibitors
干预措施: Dolutegravir (Drug)
SOC arm
Standard of Care (SOC) for ODYSSEY A is defined as a PI or non nucleoside transcriptase inhibitors + 2 or 3 nucleoside transcriptase inhibitor SOC for ODYSSEY B is defined as a PI or non nucleoside transcriptase inhibitor+ 2 nucleoside transcriptase inhibitors
干预措施: Standard of Care (Drug)
结局指标
主要结局
Difference in Proportion With Failure (Clinical or Virological)
时间窗: 96 weeks post randomisation
Treatment failure by 96 weeks. Estimated using time to the first occurrence of any of the following components: * Insufficient virological response defined as \< 1 log10 drop at week 24 and switch to second/third line ART for treatment failure * Viral Load (VL)\>400 c/ml at or after 36 weeks confirmed by next visit * Death due to any cause * Any new or recurrent AIDS defining event (WHO 4) or severe WHO 3 events, adjudicated by the Endpoint Review Committee
次要结局
- HIV-1 RNA <50c/ml at 96 Weeks(96 weeks post randomisation)
- Mean Change in Total Cholesterol From Baseline to Week 96(96 weeks post randomisation)
- Grade 3 or Above Clinical and Laboratory Adverse Events(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- HIV-1 RNA <400c/mL at 96 Weeks(96 weeks post randomisation)
- Serious Adverse Events(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- Treatment Failure by 48 Weeks(48 weeks post randomisation)
- Mean Change in CD4 Count From Baseline to Week 96(96 weeks post randomisation)
- Adverse Events Leading to ART Modification Any Grade(Randomised Phase)
- Treatment Failure by 144 Weeks(144 weeks post randomisation)
- WHO 4, Severe WHO 3 Events and Death(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- Per Protocol: Treatment Failure by 96 Weeks(96 weeks post randomisation)
- NRTI Resistance After Virologic Failure(96 weeks post randomisation)
- PI Resistance After Virologic Failure(96 weeks post randomisation)
- Any Drug Class Resistance After Virologic Failure(96 weeks post randomisation)
- NNRTI Resistance After Virologic Failure(96 weeks post randomisation)
- NRTI Emerging Resistance After Virologic Failure(96 weeks post randomisation)
- NNRTI Emerging Resistance After Virologic Failure(96 weeks post randomisation)
- INSTI Resistance After Virologic Failure(96 weeks post randomisation)
- Emerging Resistance to Any Drug Class After Virologic Failure(96 weeks post randomisation)
- Health-related Quality of Life Questionnaire(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- PI Emerging Resistance After Virologic Failure(96 weeks post randomisation)
- INSTI Emerging Resistance After Virologic Failure(96 weeks post randomisation)
- Time to Any New or Recurrent AIDS Defining Event (WHO 4) or Severe WHO 3 Events(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- Adherence Questionnaire(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)
- Acceptability Questionnaire(Randomised phase: follow-up was censored when the last participant reached 96 weeks of follow-up (142 weeks (IQR:124 to 159) in ≥14kg cohort and 124 weeks (112 to 137) in <14kg cohort).)