Microscopic polyangiitis, ANCA vasculitis Musculoskeletal Diseases Microscopic polyangiitis
Conditions
Interventions
Participants who have Granulomatosis with Polyangiitis, Microscopic Polyangiitis or Eosinophilic Granulomatosis with Polyangiitis will be recruited from 10 sites over 2 years. Participants will be ran
Sponsors
Guy's and St Thomas' NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients: 1. Aged =18 years at screening 2. Clinical diagnosis of Granulomatosis Polyangiitis (GPA), Microscopic Polyangiitis (MPA), or Eosinophilic Granulomatosis with Polyangiitis (EGPA) according to the Chapel Hill criteria 3. Birmingham Vasculitis Activity Score (BVAS v.3) >3 with minor BVAS items only (no major BVAS items) at screening and randomisation 4. Receiving maintenance therapy at a stable dose for 4 weeks prior to randomisation 5. If receiving corticosteroids for reasons other than vasculitis must be on a stable regimen for 4 weeks prior to randomisation 6. Not pregnant or nursing. Is either: not of non-childbearing potential, for example, is postmenopausal (1 year without menses), or has had a hysterectomy, bilateral oophorectomy, documented tubal ligation, or other permanent sterilization procedure; or is of childbearing potential and has a negative urine pregnancy test at screening and at baseline and agrees to using an effective method of contraception. Periodic abstinence (calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Partcipants of childbearing potential must consistently and correctly use of one of the following acceptable methods of birth control for 1 month prior to the start of the study agent, during the study, and 16 weeks after the last dose of study agent: 6.1. Oral contraceptive, either combined or progestogen alone 6.2. Injectable progestogen 6.3. Implants of levonorgestrel or etonogestrel 6.4. Estrogenic vaginal ring 6.5. Percutaneous contraceptive patches 6.6. Intrauterine device (IUD) or intrauterine system (IUS) with <1% failure rate as stated in the product label 7. No contraindications to hydroxychloroquine therapy and normal baseline visual fields at screening 8. Willing and able to give written informed consent to participate in the trial 9. Patients should have sufficient understanding of the English language to provide informed consent and complete the patient questionnaires 10. Negative urine drug screen should be performed prior to study entry
Exclusion criteria
Exclusion criteria: 1. Currently taking hydroxychloroquine or related antimalarial such as mepacrine or chloroquine 2. Estimated Glomerular Filtration Rate (eGFR) 470 msec (female participants) or >450 msec (male participants) demonstrated by at least two ECGs. 17. Participation in any other interventional trial within the last 6 months 18. Current symptomatic COVID-19 infection 19. Have been admitted to the ICU in the past 6 months due to a COVID-19 infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of patients with uncontrolled AAV disease activity measured using Birmingham Vasculitis Activity Score (BVAS), prednisolone dose records, and medication records at 44, 48, 52, and 56 weeks. Uncontrolled AAV is defined as one of the following: 1. BVAS >3) 2. BVAS =3, but prednisolone for AAV >7.5 mg daily 3. BVAS =3, but corticosteroid use for any reason >7.5 mg daily at any point during the final 12 weeks of the study (±7 days). Inhaled corticosteroids will not contribute to the primary endpoint, nor will methylprednisolone given for rituximab maintenance therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Cumulative number of visits where BVAS=0 (excluding screening, baseline and week 56) measured using Birmingham Vasculitis Activity Score (BVAS) at 4, 16, 28, 40, 44, 48, and 52 weeks 2. Proportion of patients with treatment failure at week 52 measured from the incidence of death due to vasculitis disease activity or a severe disease flare resulting in organ failure or critical care admission at 52 weeks 3. Cumulative prednisolone dosage measured using prednisolone dose records at baseline, 4, 16, 28, 40, 44, 48, 52, and 56 weeks 4. Total number of adverse events measured using adverse event records at baseline, 4, 10, 16, 22, 28, 34, 40, 44, 48, 52, and 56 weeks 5. Total number of infections per patient measured using physician history and examination, and investigations at baseline, 4, 16, 28, 40, 44, 48, 52, and 56 weeks 6. Total number of vasculitis flares per patient (excluding screening, baseline and week 56) measured using BVAS at 4, 16, 28, 40, 44, 48, and 52 weeks 7. Time to remission measured using BVAS at baseline, 4, 16, 28, 40, 44, 48, 52, and 56 weeks where BVAS =0 on two consecutive visits 8. Time to first limited flare measured using BVAS at baseline, 4, 16, 28, 40, 44, 48, 52, and 56 weeks where a new or worsening minor item is present on the BVAS with no new major items 9. Time to first severe flare measured using BVAS at baseline, 4, 16, 28, 40, 44, 48, 52, and 56 weeks where a new or worsening major item on the BVAS is present 10. Proportion of patients categorized as having a severe flare at each time point in the trial schedule (excluding screening, baseline and week 56) measured using BVAS at 4, 16, 28, 40, 44, 48, and 52 weeks 11. Proportion of patients categorized as having a limited flare at each time point in the trial schedule (excluding screening, baseline and week 56) measure | — |
Countries
England, United Kingdom, Wales
Outcome results
None listed