ACT4RHD is an Open-label, Randomised, Adaptive Platform Trial to Evaluate Novel and Repurposed Clinical Interventions for Patients With Acute Rheumatic Fever and Carditis. ACT4RHD Seeks to Determine Whether These Interventions Reduce RHD Severity at 6 Months. (ACT4RHD)
ACT4RHD: Adaptive Collaborative Trial for Rheumatic Heart Disease
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.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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:
- That corticosteroids administered to children and young adults with ARF affecting the mitral and/or aortic valve will be safe and will reduce valve inflammation (that is, carditis) in rheumatic fever;
- That hydroxychloroquine treatment administered to children and young adults with ARF affecting the mitral and/or aortic valve will be safe and will reduce valve inflammation in rheumatic fever;
- That reduction in carditis severity and/or duration, will be associated with reduction in valve scarring and dysfunction, measured by an echocardiographic RHD severity grade at 6 months;
- That reduction in carditis will be associated with lower RHD severity at 12 months, and with improved patient-centered outcomes;
- That the development of a durable ARF platform trial will allow several investigational products and management approaches to be tested in a robust and rigorous fashion over the coming years.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Rachel Webb
- Número de teléfono: +64093074949
- Correo electrónico: ACT4RHD@TeWhatuOra.govt.nz
Copia de seguridad de contactos de estudio
- Nombre: Anna Ralph
- Correo electrónico: Anna.Ralph@menzies.edu.au
Ubicaciones de estudio
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Northern Territory
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Darwin, Northern Territory, Australia, 0811
- Royal Hospital
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Contacto:
- Anna Ralph
- Correo electrónico: Anna.Ralph@menzies.edu.au
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Auckland, Nueva Zelanda, 1023
- Starship Child Health, Te Toka Tumai, Auckland
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Contacto:
- Rachel Webb
- Correo electrónico: Rachel.Webb2@TeWhatuOra.govt.nz
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Auckland, Nueva Zelanda, 2104
- KidzFirst Hospital
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Contacto:
- Rachel Webb
- Correo electrónico: Rachel.Webb2@TeWhatuOra.govt.nz
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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).
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación factorial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Otro: Immunomodulatory Domain
Hydroxychloroquine (HCQ) as per standardised dosing table for 12 weeks OR No hydroxychloroquine (no placebo) |
Hydroxychloroquine (HCQ) No Hydroxychloroquine (HCQ) |
|
Otro: 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) |
With or without initial pulsed Methylprednisolone / oral dexamethasone No corticosteroid |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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6-point ordinal scale
Periodo de tiempo: 6 months from enrolment
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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. |
6 months from enrolment
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades musculoesqueléticas
- Enfermedades cardiovasculares
- Enfermedades cardíacas
- Artritis
- Enfermedades Articulares
- Enfermedades reumáticas
- Enfermedades del tejido conectivo
- Infecciones
- Infecciones por bacterias grampositivas
- Infecciones bacterianas
- Infecciones bacterianas y micosis
- Infecciones estreptocócicas
- Enfermedades de la piel y del tejido conectivo
- Fiebre reumática
- Enfermedad reumática del corazón
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Compuestos policíclicos
- Espierra
- Embarazos
- Esteroides
- Compuestos de anillo fusionado
- Esparrazadienetrioles
- Madreadiediols
- Quinolinas
- Aminoquinolinas
- Cloroquina
- Prednisona
- Prednisolona
- Hidroxicloroquina
Otros números de identificación del estudio
- 22-442
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
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