Reduction of Early mortALITY in HIV-infected African Adults and Children Starting Antiretroviral Therapy: a Randomised Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,805
- 试验地点
- 8
- 主要终点
- All-cause mortality over the first 24 weeks after starting ART
研究概览
简要总结
A randomised controlled trial to investigate three methods to reduce early mortality in adults, adolescents and children aged 5 years or older starting antiretroviral therapy (ART) with severe immuno-deficiency. The three methods are:
(i) increasing the potency of ART with a 12 week induction period using 4 antiretroviral drugs from 3 classes
(ii) augmented prophylaxis against opportunistic/bacterial infections and helminths for 12 weeks
(iii) macronutrient intervention using ready-to-use supplementary food for 12 weeks.
详细描述
REALITY is a open-label randomised trial of 1800 adults, adolescents and children aged 5 years or more with low CD4 counts about to initiate ART.
The trial will have a factorial design with 3 randomisations, each to address one of the potential approaches to reduce early mortality in adults and children initiating ART with low CD4, namely:
- Raltegravir for 12 weeks from ART initiation in addition to 3 standard ART (3-drug 2-class) versus standard of care first-line 3-drug 2-class ART (choice according to national guidelines for ART initiation);
- Immediate enhanced opportunistic infections (OI) prophylaxis with isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole versus cotrimoxazole prophylaxis alone for the first 12 weeks followed by isoniazid and any prophylaxis and/or treatment prescribed at screening
- supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks versus standard of care nutritional support to those with poor nutritional status according to local guidelines.
All participants will receive cotrimoxazole throughout the trial.
The primary objective of the trial is to identify effective, safe and acceptable interventions to reduce early mortality (all-cause) in HIV-infected adults, adolescents, and older children (5 years or more) initiating ART.
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 5 years or older
- •Documented HIV infection by HIV ELISA or HIV rapid test
- •Naive to ART
- •CD4 T-cell count <100 cells/mm3 on blood test taken at screening for REALITY
- •Results of screening haematology and biochemistry tests available and no contraindications to planned ART according to national guidelines
- •Patient/carer provide informed consent (and children <18 years assent, as appropriate according to their age and knowledge of HIV status)
- •The lower age limit is because CD4 counts are less reliable predictors of immunodeficiency under 5 years: CD4 counts are recommended by guidelines in older children.
- •No patient with a CD4 count above 100 cells/mm3 should have ART delayed in order to subsequently meet eligibility criteria. Rather, patients eligible for REALITY will be those testing HIV positive for the first time with a low CD4 count (i.e. those delaying presentation to care), or those who have defaulted before initiating ART and only return to care at an advanced stage of immuno-deficiency.
排除标准
- •Contraindications to any proposed antiretroviral drugs (including integrase inhibitors), isoniazid, fluconazole, albendazole or azithromycin
- •Pregnant or breastfeeding or intending to become pregnant during the first 12 weeks of the study
- •Ever known to have previously received single-dose nevirapine for prevention of mother-to-child transmission (mother or child).
研究组 & 干预措施
Opportunistic Infection (OI) Prophylaxis
Immediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
干预措施: Albendazole (Drug)
Opportunistic Infection (OI) Prophylaxis
Immediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
干预措施: Isoniazid (Drug)
Nutritional Support
Supplementation with Ready to Use Supplementary Food (RUSF) for 12 weeks compared with supplementation for those with severe malnutrition as local practice.
干预措施: Ready to Use Supplementary Food (Dietary Supplement)
Antiretroviral Therapy
Raltegravir twice daily for 12 weeks from antiretroviral therapy (ART) initiation in addition to 3 standard ARVs (2NRTIs/1NNRTI) compared with 3 standard ARVs
干预措施: Raltegravir (Drug)
Opportunistic Infection (OI) Prophylaxis
Immediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
干预措施: Fluconazole (Drug)
Opportunistic Infection (OI) Prophylaxis
Immediate isoniazid/pyridoxine and cotrimoxazole, plus 12 weeks fluconazole, 5 days azithromycin and a single dose of albendazole compared with immediate cotrimoxazole (if not already taking this) in all patients plus (not malawi)isoniazid/pyridoxine after 12 weeks.
干预措施: Azithromycin (Drug)
结局指标
主要结局
All-cause mortality over the first 24 weeks after starting ART
时间窗: Week 24
次要结局
- Safety(Week 0-48)
- Hospital inpatient episodes and total days admitted(Week 0-48)
- Adherence to ART and acceptability of each strategy(Week 0-48)
- Endpoint relating to anti-malnutrition intervention(0-48 weeks)
- Endpoint relating to anti-infection intervention(0-48 weeks)
- Endpoint relating to anti-HIV intervention(0-48 weeks)
- 48 week mortality (all-cause)(Week 48)
研究者
Anna Griffiths, MRC
Trial Manager
Medical Research Council