Rheumatic Heart Disease in ChildrenPhase 2AGRAF-2NCT05682196
Rituximab in Patients With Acute Rheumatic Fever
A Phase 2 study of Rheumatic Heart Disease in Children, run by African Academy of Methodology and Statistics at 1 site in Senegal.
Trial summary
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Read more about this study
- Who is it for?
- Ages 5 to 17 years
- Conditions the study is for
- Rheumatic Heart Disease in Children
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 234 participants
- Where
- 1 siteSenegal
- Study dates
- 5 Jan 2023to 1 Feb 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 5 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children aged between >= 5 and < 17 years old;
- Diagnosed acute rheumatic fever with at least one progressive rheumatic valvular lesion confirmed through a cardiac echography.
- Informed consent, signed and dated by both parents or legal guardians of the patient
Who cannot join
- Simultaneous active infection, such as HIV, hepatitis B, C, tuberculosis, Epstein-Barr virus (EBV), or history of frequent, unusual or serious infections ;
- Pathologies likely to affect immunity (cancer, multiple sclerosis, diabetes, other auto-immune diseases)
- Recent history of drug administration that may affect the immune system, for the past 4 weeks (immunosuppressive drugs, corticosteroids, anticancer drugs);
- Hypersensitivity reaction to rituximab or one of its components. Hypersensitivity to penicillin
- History of monoclonal antibodies administration
- Recent vaccination (less than a month) or planned within the 12 months after randomization;
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- History of heart failure
- Renal failure with a creatinine clearance <45 ml/min/1,73m²
- Pregnancy (a negative urinary test is necessary for women who had their first menstruations or aged 14 years old and more)
- Patients diagnosed with Guillain-Barré syndrome
- Patient with at least one of the following biological features : Hemoglobin < 8,5 g/dL, Platelets < 100 G/L, Neutrophils < 1,5 G/L, Leucocytes < 3 G/L, AST or ALT increased > 2,5 the normal superior limit)
- Any acute or chronic infection clinically significant which would limitate the patient's capacity to follow up the study protocol, which remains under appreciation of the investigator.
- Any participation in another clinical trial in the 6 months before the pre-randomization visit
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open-label, Randomized Controlled Trial to Assess Efficacy and Safety of Rituximab in Patients With Acute Rheumatic Fever in Africa
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
Read the detailed description
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis (which associates valvular leakages, cardiac conduction system troubles, and pericardial signs), combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Prevalence of acute rheumatic disease (ARD) in pproximately 6 cases per 1000 children in Sub-Saharan Africa countries, whereas prevalence in developed countries is less than a case per 100 000 children, with an annual incidence of 470 000 cases and almost 230 000 deaths annually worldwide. Carditis affect between 15 and 20 million people worldwide, mostly children and young adults from low and middle-income countries. This prevalence may be underestimated. In 2007, our team conducted a study in Mozambique and Cambodia that highlighted that, through a screening based on systematic echocardiography in children from several schools, approximately 2/3 of them had asymptomatic and unknown cardiac lesions, which cannot be screened only with a clinical examination. Role of B-type lymphocytes (B cells) in auto-immune diseases physiopathology is nowadays largely accepted and justifies, in certain auto-immune diseases, the use of therapeutics that target and destroy B cells. Rituximab is a CD-20-specific monoclonal chimeric antibody, indicated to treat B lymphomas, where its efficacy and safety have changed the management of these diseases. Recently, it is thought to use Rituximab in auto-immune diseases. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
- Conditions
- Rheumatic Heart Disease in Children
- Being tested
- Rituximab added to standard of care treatment, standard of care treatment alone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab added to standard of care treatmentDrug
Also called Rituximab with standard of care treatment
Rituximab with standard of care treatment
standard of care treatment aloneDrug
Standard of care treatment alone
| Study group | Role | What they receive |
|---|---|---|
| Rituximab plus standard of care (RTX) | Experimental | Rituximab i.v of two perfusions (375 mg/m²) administered in a 14 day-interval added to a standard of care treatment Receives: Drug: Rituximab added to standard of care treatment |
| Standard of care treatment (Control) | Active comparator | Standard of care treatment Receives: Drug: standard of care treatment alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rheumatic valvular lesions rate
Rheumatic valvular lesions rate, measured by echocardiography
Measured: 6 months post randomization
Secondary outcomes (2)
Incidence of rheumatic valvular lesions
Rate of rheumatic valvular lesions will be compared between groups
Measured: 14 days, 3, 6 and 12 months post-randomization
Serious adverse events rates
Serious adverse events rate will be compared between groups
Measured: at 14 days, 3, 6, and 12 months after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2023
- Study start5 Jan 2023
- Primary completion30 Sep 2024 (estimated)
- Study completion1 Feb 2025 (estimated)
Why it stopped: ethical controversy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatic Heart Disease in ChildrenStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 234 participants (estimated)
Sponsor and investigators
- Lead sponsor
- African Academy of Methodology and Statistics
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05682196
- Sponsor's protocol ID
- AGRAF-2
- Acronym
- AGRAF-2
- Status last verified
- Jun 2024
- First submitted
- 15 Dec 2022
- Last updated
- 11 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label, Randomized Controlled Trial to Assess Efficacy and Safety of Rituximab in Patients With Acute Rheumatic Fever in Africa
- ClinicalTrials.gov ID
- NCT05682196
- Acronym / sponsor ID
- AGRAF-2 / AGRAF-2
- Conditions
- Rheumatic Heart Disease in Children
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: ethical controversy
- Enrolment
- 234 participants (estimated)
- Lead sponsor
- African Academy of Methodology and StatisticsUniversity, hospital or other
- Study start
- 5 Jan 2023 (actual)
- Primary completion
- 30 Sep 2024 (estimated)
- Study completion
- 1 Feb 2025 (estimated)
- First posted
- 12 Jan 2023 (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.
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
Detailed description
Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis (which associates valvular leakages, cardiac conduction system troubles, and pericardial signs), combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Prevalence of acute rheumatic disease (ARD) in pproximately 6 cases per 1000 children in Sub-Saharan Africa countries, whereas prevalence in developed countries is less than a case per 100 000 children, with an annual incidence of 470 000 cases and almost 230 000 deaths annually worldwide. Carditis affect between 15 and 20 million people worldwide, mostly children and young adults from low and middle-income countries. This prevalence may be underestimated. In 2007, our team conducted a study in Mozambique and Cambodia that highlighted that, through a screening based on systematic echocardiography in children from several schools, approximately 2/3 of them had asymptomatic and unknown cardiac lesions, which cannot be screened only with a clinical examination. Role of B-type lymphocytes (B cells) in auto-immune diseases physiopathology is nowadays largely accepted and justifies, in certain auto-immune diseases, the use of therapeutics that target and destroy B cells. Rituximab is a CD-20-specific monoclonal chimeric antibody, indicated to treat B lymphomas, where its efficacy and safety have changed the management of these diseases. Recently, it is thought to use Rituximab in auto-immune diseases. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab plus standard of care (RTX) | Experimental | Drug: Rituximab added to standard of care treatmentRituximab i.v of two perfusions (375 mg/m²) administered in a 14 day-interval added to a standard of care treatment |
| Standard of care treatment (Control) | Active comparator | Drug: standard of care treatment aloneStandard of care treatment |
Who may qualify
- Ages
- 5 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Children aged between >= 5 and < 17 years old;
- Diagnosed acute rheumatic fever with at least one progressive rheumatic valvular lesion confirmed through a cardiac echography.
- Informed consent, signed and dated by both parents or legal guardians of the patient
Key exclusion criteria (13 listed)
- Simultaneous active infection, such as HIV, hepatitis B, C, tuberculosis, Epstein-Barr virus (EBV), or history of frequent, unusual or serious infections ;
- Pathologies likely to affect immunity (cancer, multiple sclerosis, diabetes, other auto-immune diseases)
- Recent history of drug administration that may affect the immune system, for the past 4 weeks (immunosuppressive drugs, corticosteroids, anticancer drugs);
- Hypersensitivity reaction to rituximab or one of its components. Hypersensitivity to penicillin
- History of monoclonal antibodies administration
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 |
|---|---|---|
| Rituximab added to standard of care treatmentAlso: Rituximab with standard of care treatmentRituximab with standard of care treatment | Drug | Rituximab plus standard of care (RTX) |
| standard of care treatment aloneStandard of care treatment alone | Drug | Standard of care treatment (Control) |
Primary outcome
Rheumatic valvular lesions rate
Time frame: 6 months post randomization
Rheumatic valvular lesions rate, measured by echocardiography
2 secondary outcomes
Incidence of rheumatic valvular lesions
Time frame: 14 days, 3, 6 and 12 months post-randomization
Serious adverse events rates
Time frame: at 14 days, 3, 6, and 12 months after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Rheumatic Heart Disease in Children, run by African Academy of Methodology and Statistics at 1 site in Senegal.
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 3 inclusion and 13 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: paused, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Senegal. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rheumatic valvular lesions rate (time frame: 6 months post randomization). 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 11 Jun 2024.