Rituximab in Patients With Acute Rheumatic Fever

NCT ID: NCT05682196

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 234 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-05
• Study Completion Date: 2025-02-01

Brief 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. 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.

Conditions

Rheumatic Heart Disease in Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Rituximab plus standard of care (RTX)

Rituximab i.v of two perfusions (375 mg/m²) administered in a 14 day-interval added to a standard of care treatment

Group Type: EXPERIMENTAL

Rituximab added to standard of care treatment

Intervention Type: DRUG

Rituximab with standard of care treatment

Standard of care treatment (Control)

Standard of care treatment

Group Type: ACTIVE_COMPARATOR

standard of care treatment alone

Intervention Type: DRUG

Standard of care treatment alone

Interventions

Rituximab added to standard of care treatment

Rituximab with standard of care treatment

Intervention Type: DRUG

standard of care treatment alone

Standard of care treatment alone

Intervention Type: DRUG

Other Intervention Names

Rituximab with standard of care treatment

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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;
• 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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

African Academy of Methodology and Statistics

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Fann Hospital

Dakar, , Senegal

Countries

Senegal

Other Identifiers

AGRAF-2

Identifier Type: -

Identifier Source: org_study_id