Rheumatic FeverPhase 3ACT4RHDNCT07830108
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.
A Phase 3 study testing Hydroxychloroquine (HCQ), No Hydroxychloroquine (HCQ) and Prednisone or Prednisolone in people with Rheumatic Fever and Rheumatic Heart Disease in Children, run by Starship Child Health, Te Toka Tumai Auckland at 3 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 to 25 years
- Conditions the study is for
- Rheumatic Fever, Rheumatic Heart Disease in Children, Acute Rheumatic Fever
- What is being tested?
- Hydroxychloroquine (HCQ), No Hydroxychloroquine (HCQ) and Prednisone or Prednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Dec 2026to Dec 2036
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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).
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Anna Ralph contact
3 sites in 2 countries
New Zealand2 sites
Starship Child Health, Te Toka Tumai, Auckland
Auckland, 1023
Rachel Webb, Rachel.Webb2@TeWhatuOra.govt.nz
KidzFirst Hospital
Auckland, 2104
Rachel Webb, Rachel.Webb2@TeWhatuOra.govt.nz
Australia1 site
Royal Hospital
Darwin, Northern Territory, 0811
Anna Ralph, Anna.Ralph@menzies.edu.au
About this study
Official title: 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.
Read the detailed description
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.
- Conditions
- Rheumatic Fever, Rheumatic Heart Disease in Children, Acute Rheumatic Fever, Rheumatic Heart Disease
- Being tested
- Hydroxychloroquine (HCQ), No Hydroxychloroquine (HCQ), Prednisone or Prednisolone, No corticosteroid
- Keywords
- Adaptive platform
- Medical subject headings
- Rheumatic Fever, Rheumatic Heart Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine (HCQ)Drug
Hydroxychloroquine (HCQ)
No Hydroxychloroquine (HCQ)Other
No Hydroxychloroquine (HCQ)
Prednisone or PrednisoloneDrug
With or without initial pulsed Methylprednisolone / oral dexamethasone
No corticosteroidOther
No corticosteroid
| Study group | Role | What they receive |
|---|---|---|
| Immunomodulatory Domain | Other | Hydroxychloroquine (HCQ) as per standardised dosing table for 12 weeks
OR
No hydroxychloroquine (no placebo) Receives: Drug: Hydroxychloroquine (HCQ); Other: No Hydroxychloroquine (HCQ) |
| Corticosteroid domain | Other | 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) Receives: Drug: Prednisone or Prednisolone; Other: No corticosteroid |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-point ordinal scale
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.
Measured: 6 months from enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2026
- Study startDec 2026 (estimated)
- Primary completionDec 2034 (estimated)
- Study completionDec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatic FeverStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Starship Child Health, Te Toka Tumai Auckland
- Sponsor type
- Other government
- Collaborators
- Menzies School of Health Research, Berry Consultants
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07830108
- Sponsor's protocol ID
- 22-442
- Acronym
- ACT4RHD
- Status last verified
- Oct 2026
- First submitted
- 15 Sep 2026
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ACT4RHD: Adaptive Collaborative Trial for Rheumatic Heart Disease
- ClinicalTrials.gov ID
- NCT07830108
- Acronym / sponsor ID
- ACT4RHD / 22-442
- Conditions
- Rheumatic Fever, Rheumatic Heart Disease in Children, Acute Rheumatic Fever, Rheumatic Heart Disease
- Keywords
- Adaptive platform
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Starship Child Health, Te Toka Tumai AucklandOther government
- Collaborators
- Menzies School of Health Research, Berry Consultants
- Study start
- Dec 2026 (estimated)
- Primary completion
- Dec 2034 (estimated)
- Study completion
- Dec 2036 (estimated)
- First posted
- 21 Sep 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunomodulatory Domain | Other | Drug: Hydroxychloroquine (HCQ), Other: No Hydroxychloroquine (HCQ)Hydroxychloroquine (HCQ) as per standardised dosing table for 12 weeks OR No hydroxychloroquine (no placebo) |
| Corticosteroid domain | Other | Drug: Prednisone or Prednisolone, Other: No corticosteroidCorticosteroids. 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) |
Who may qualify
- Ages
- 4 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine (HCQ)Hydroxychloroquine (HCQ) | Drug | Immunomodulatory Domain |
| No Hydroxychloroquine (HCQ)No Hydroxychloroquine (HCQ) | Other | Immunomodulatory Domain |
| Prednisone or PrednisoloneWith or without initial pulsed Methylprednisolone / oral dexamethasone | Drug | Corticosteroid domain |
| No corticosteroidNo corticosteroid | Other | Corticosteroid domain |
Primary outcome
6-point ordinal scale
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Ralph contact
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hydroxychloroquine (HCQ), No Hydroxychloroquine (HCQ) and Prednisone or Prednisolone in people with Rheumatic Fever and Rheumatic Heart Disease in Children, run by Starship Child Health, Te Toka Tumai Auckland at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in New Zealand, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rachel Webb (+64093074949, ACT4RHD@TeWhatuOra.govt.nz), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
6-point ordinal scale (time frame: 6 months from enrolment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.