ACT4RHD: Adaptive Collaborative Trial for Rheumatic Heart Disease
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 600
- 试验地点
- 2
- 主要终点
- 6-point ordinal scale
研究概览
简要总结
The ACT4RHD trial is a multicentre, pragmatic, multi-arm, open-label adaptive platform trial addressing multiple therapeutic questions in patients with ARF and carditis. ACT4RHD aims to improve health outcomes for children and young people affected by ARF by finding treatments to reduce heart damage. The trial's Bayesian adaptive design enables multiple promising treatments to be tested at the same time. The trial will adapt by stopping treatments that are not effective sooner than traditional trials, adding new treatments as they become available, and answering research questions as soon as enough evidence has been collected. This flexibility allows researchers to identify the most effective treatments more quickly than traditional clinical trials.
详细描述
Background: Acute rheumatic fever (ARF) is a major health priority in lower-middle income countries (LMIC) and for Indigenous and underserved populations in high income countries including Australia and New Zealand. It is an autoimmune condition of childhood triggered by Strep A infection, leading to rheumatic heart disease (RHD). RHD affects more than 40 million people globally, resulting in approximately 310,000 deaths each year. There are currently no proven anti-inflammatory or immune modulating therapies to limit cardiac damage during ARF to prevent RHD. The only treatment is antibiotics (penicillin) given after ARF is diagnosed, to prevent recurrent streptococcal infections that drive ARF recurrences and progression of RHD.
Design: ACT4RHD is a randomized, multifactorial, open label adaptive platform trial with blinded end- point assessment. At trial launch, domains will comprise a Corticosteroid domain and an Immunomodulatory Domain. The treatment intervention in the Corticosteroid domain will include 4 to 6 weeks of corticosteroids or a no-corticosteroid control.
Treatment for the Immunomodulatory domain includes hydroxychloroquine for 12 weeks compared to a no-hydroxychloroquine control.
These are interventions are prescribed open label in addition to standard care. The primary endpoint is a 6-point ordinal scale which comprises RHD severity (measured by echocardiography), need for rheumatic cardiac surgery or death at 6 months.
Aims: The overarching aim of ACT4RHD is to alleviate suffering from ARF and reduce the prevalence and severity of RHD which arises from ARF. Trial hypotheses at launch:
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
- 4 Years 至 25 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥4 and ≤25 years old
- •Currently admitted to hospital, or hospital like setting, with the primary diagnosis of Definite or Possible Acute Rheumatic Fever (diagnosed according to the 2015 Jones Criteria)
- •Echocardiographic confirmed valvulitis during the current admission
- •If previous participation in the randomised ACT4RHD platform, then meets pre-specified criteria for re-enrolment
- •Patient expected to be able to complete protocol-required follow up assessments to 6 months post-enrolment
排除标准
- •Presentation to current hospital was more than 10 days prior to randomisation
- •Cardiac surgery (or anticipated interhospital transfer for cardiac surgery) or death is anticipated within 72 hours from screening
- •Patient has had cardiac intervention (surgery or percutaneous) for RHD within the last 6 months
- •Previous cardiac intervention /surgery for RHD more than 6months ago, but patient has not had at least 2 post-intervention echocardiograms, including at least 1 echocardiogram more than 6months after the intervention.
- •Each domain will have additional eligibility criteria. Refer to the appliable Domain Specific Appendix (DSA).
研究组 & 干预措施
Immunomodulatory Domain
Hydroxychloroquine (HCQ) as per standardised dosing table for 12 weeks
OR
No hydroxychloroquine (no placebo)
干预措施: No Hydroxychloroquine (HCQ) (Other)
Immunomodulatory Domain
Hydroxychloroquine (HCQ) as per standardised dosing table for 12 weeks
OR
No hydroxychloroquine (no placebo)
干预措施: Hydroxychloroquine (HCQ) (Drug)
Corticosteroid domain
Corticosteroids. Corticosteroid strategy:
Mild carditis:
Prednis(ol)one 2mg/kg once daily for 2 weeks, followed by a taper over 2 weeks according to standard tables
Moderate and severe carditis:
Three days of high-dose, pulsed corticosteroid (IV methylprednisolone or oral dexamethasone), followed by Prednis(ol)one 2mg/kg once daily for 2 weeks, followed by a taper over 4 weeks according to standard tables
OR
No corticosteroid (no placebo)
干预措施: No corticosteroid (Other)
Corticosteroid domain
Corticosteroids. Corticosteroid strategy:
Mild carditis:
Prednis(ol)one 2mg/kg once daily for 2 weeks, followed by a taper over 2 weeks according to standard tables
Moderate and severe carditis:
Three days of high-dose, pulsed corticosteroid (IV methylprednisolone or oral dexamethasone), followed by Prednis(ol)one 2mg/kg once daily for 2 weeks, followed by a taper over 4 weeks according to standard tables
OR
No corticosteroid (no placebo)
干预措施: Prednisone or Prednisolone (Drug)
结局指标
主要结局
6-point ordinal scale
时间窗: 6 months from enrolment
The primary endpoint is a 6-point ordinal scale which comprises RHD severity (measured by echocardiography), need for rheumatic cardiac surgery or death at 6 months.
次要结局
未报告次要终点