Mycophenolate mofetil versus cyclophosphamide for the induction of remission of childhood polyarteritis nodosa
- Conditions
- Polyarteritis nodosaMusculoskeletal Diseases
- Registration Number
- ISRCTN75434563
- Lead Sponsor
- niversity College London (UK)
- Brief Summary
2021 Results article in https://pubmed.ncbi.nlm.nih.gov/33760371/ (added 21/09/2021)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 11
1. Age at screening = 4 and = 18 years
2. Children to be included must fulfil the new EULAR/PRINTO/PReS classification criteria for childhood systemic PAN (4) as defined by: Histopathological evidence of necrotising vasculitis in medium- or small-sized arteries or angiographic abnormality as a mandatory criterion (4); plus one of the following five:
2.1. Skin involvement
2.2. Myalgia or muscle tenderness
2.3. Hypertension
2.4. Peripheral neuropathy
2.5. Renal involvement
3. Newly diagnosed* and with active disease that would normally require treatment with CYC:
3.1. One or more of major PVAS items (see below)
3.2. and/or three or more minor PVAS items
3.3. and/or either of the two additional entry criteria:
3.3.1. Severe systemic inflammation and/or features of macrophage activation syndrome due to PAN where the
investigator would routinely use cyclophosphamide
3.3.2. Demonstration of severe angiographic changes consistent with systemic PAN with other compatible clinical features, but not necessarily including the major PVAS items listed above
4. Written informed consent for study participation obtained from the patient or parents/legal guardian, with assent as appropriate by the patient, depending on the level of understanding.
Sufficient disease activity for trial entry (see inclusion criteria 3 above) requires at least one major or three minor PVAS
items as listed below, and/or at least one of the additional criteria listed:
Major PVAS items:
Trial entry criteria or major relapse require the recurrence or new appearance of major organ involvement, if they are
attributable to active vasculitis:
1. Severe cutaneous vasculitis: significant infarct, ulcer or gangrene. Other significant cutaneous vasculitis such as widespread bullous vasculitic skin disease would also be an inclusion criterion
2. Threatened vision from any of: retinal vasculitis, retinal vessel thrombosis, scleritis, retinal exudates, or retinal haemorrhages
3. Major chest involvement: major pulmonary bleeding, with shifting pulmonary infiltrates; other causes of bleeding should be excluded if possible
4. Cardiovascular involvement: loss of pulses, bruits over accessible arteries, blood pressure discrepancy more than 10 mmHg in any limb, claudication of extremities, ischaemic cardiac pain, cardiomyopathy, congestive cardiac failure, valvular heart disease, pericarditis
5. Abdominal involvement: abdominal pain, blood in stools or bloody diarrhoea, or bowel ischaemia. Pancreatitis, whilst not specifically listed as a PVAS item, would also be an indication for inclusion
6. Renal involvement: hypertension, significant proteinuria, significant haematuria (if microscopic haematuria > 5 red
blood cells per high power field, or red cell casts), GFR < 80 ml/min/1.73m2 , rise in creatinine > 10% or creatinine
clearance (GFR) fall > 25%. Biopsy is strongly recommended for recurrent haematuria or unexplained rise in creatinine
EXCEPT where large renal arterial aneurysms have been demonstrated
7. Nervous system
Exclusions related to vasculitis type and/or severity
1. Diagnosis of alternative vasculitic syndrome e.g. HSP, or ANCA vasculitis
2. Patients requiring dialysis
Exclusions related to general health
3. Evidence of other significant uncontrolled concomitant disease that in the investigator?s view would preclude or interfere with patient participation. This will be recorded in the screening log
4. Primary or secondary immunodeficiency including known history of human immunodeficiency virus (HIV) infection
5. Known active and/or chronic infection of any kind (excluding fungal nail and/or minor fungal skin infections)
6. History of serious recurrent or chronic infection including tuberculosis (a screening chest radiograph will be performed if not performed within 12 weeks prior to randomisation)
7. History of cancer, including solid tumours, haematologic malignancies and carcinoma in situ
8. Participation in a clinical trial testing a medicinal product within 3 months (12 weeks) preceding randomisation for the MYPAN trial
Exclusions related to medication
9. History of a severe allergic or anaphylactic reaction to any of the study medications or their excipients
10. More than 3 g of IV methylprednisolone within 1 month (4 weeks) prior to randomisation
11. More than 3 weeks of oral prednisolone/prednisone at dose of 2 mg/kg once daily within 1 month (4 weeks) prior
to randomisation
12. Treatment with MMF or azathioprine for more than 2 weeks; or more than one intravenous dose of cyclophosphamide (>500 mg/m2) within 1 month (4 weeks) prior to randomisation
13. Rituximab or high dose intravenous immunoglobulin within the last 12 months (48 weeks)
14. Intolerance or contraindications to intravenous glucocorticoids
15. Participant of reproductive potential not prepared to use a reliable means of contraception (e.g. hormonal contraceptive patch, intrauterine device, physical barrier) throughout study participation
a. Sexually active female not prepared to use two reliable forms of contraception for the complete duration of the trial
Exclusions related to laboratory findings
16. Positive urine human chorionic gonadotropin (hCG) measured at screening (if appropriate) or a positive urine pregnancy test prior to study entry or breastfeeding
17. Positive tests for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology at randomisation
18. Absolute neutrophil count <1.5 x 10^9/l
19. Estimated GFR <15 mL/min/1.73m2 (calculated using the Schwartz GFR formula)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Remission within 6 months of randomisation defined as PVAS (modified paediatric BVAS) of zero on two consecutive readings = 1 month apart, with adherence to the protocolised corticosteroid taper
- Secondary Outcome Measures
Name Time Method ot provided at time of registration