Rituximab in Patients With Acute Rheumatic Fever

NCT05682196 | Suspended Phase 2 DMC

• 1 other identifier: AGRAF-2
• Study Type: interventional
• Target: 234
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatic Heart Disease in Children

Outcome Measures

Primary Outcomes (1)

• Rheumatic valvular lesions rate

  Rheumatic valvular lesions rate, measured by echocardiography

  6 months post randomization

Secondary Outcomes (2)

• Incidence of rheumatic valvular lesions

  14 days, 3, 6 and 12 months post-randomization

• Serious adverse events rates

  at 14 days, 3, 6, and 12 months after randomization

Study Arms (2)

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

Drug: Rituximab added to standard of care treatment

Standard of care treatment (Control)

ACTIVE COMPARATOR

Standard of care treatment

Drug: standard of care treatment alone

Interventions

Rituximab added to standard of care treatment DRUG

Rituximab with standard of care treatment

Also known as: Rituximab with standard of care treatment

Rituximab plus standard of care (RTX)

standard of care treatment alone DRUG

Standard of care treatment alone

Standard of care treatment (Control)

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• African Academy of Methodology and Statistics: lead

Study Sites (1)

Fann Hospital

Dakar, Senegal

Location

MeSH Terms

Interventions

Rituximab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 12, 2023
• Study Start: January 5, 2023
• Primary Completion: September 30, 2024
• Study Completion: February 1, 2025
• Last Updated: June 11, 2024

Record last verified: 2024-06

Locations

SE (1)