HAVEN: Hydroxychloroquine in ANCA Vasculitis Evaluation, a Phase II Multicentre, Randomised, Double Blind, Placebo Controlled Trial

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ANCA vasculitis is a life-threatening disease where the body's defence system becomes overactive, causing inflammation of small blood vessels and damage to the kidneys, lungs and other vital organs. New treatments are needed because: 1) 20% of patients do not respond to treatment. 2) In half the patients who respond, vasculitis disease activity flares when medicines are reduced. 3) The side effects of medicines can cause more problems than the disease. Safer medicines are needed for non-life threatening ANCA vasculitis, where aggressive immune suppressing treatment is not appropriate. Hydroxychloroquine has been used for many years to treat related diseases such as lupus and rheumatoid arthritis with fewer harmful effects than conventional immune suppressing drugs. It is therefore an ideal candidate to treat ANCA vasculitis. We have preliminary data from our clinics and research laboratories showing that hydroxychloroquine has effects on cells which cause inflammation of blood vessels and tissues and is therefore expected to work in treating ANCA vasculitis. We have pilot data on 30 patients with ANCA vasculitis, showing that hydroxychloroquine is well tolerated and improves symptoms of disease activity. This now needs to be confirmed in a controlled study.The potential of hydroxychloroquine to reduce infections, cancer, blood clots and heart disease are useful properties, as these risks are higher in ANCA vasculitis patients compared to the general public. To our knowledge, no studies have been published on hydroxychloroquine in ANCA vasculitis, although the benefits of hydroxychloroquine in related diseases such as lupus and rheumatoid arthritis are clear. Our proposed study aims to demonstrate that hydroxychloroquine reduces disease activity and flares, the need for steroids and their side effects, damage to vital organs and improves quality of life. 76 patients with non-severe ANCA vasculitis who meet the entry criteria for the trial will be invited to participate. After giving their informed consent, patients will be allocated by chance (like tossing a coin) by a computer to receive 2 tablets of hydroxychloroquine in addition to their usual medications (38 patients) or two placebo ("dummy") tablets (38 patients) and their usual medications. Treatment will continue for 1 year and, in order to improve the quality of the study, neither the doctors nor the patients will know if they are taking hydroxychloroquine or placebo. Patients will be seen and have blood tests and safety assessments monthly for the first and last 3 months of the study and every 3 months in between for 1 year. We plan to measure blood levels of hydroxychloroquine to assess adherence to the study medication after the study has been completed. This information will also allow correlations with the response of the disease to treatment.If the trial shows a small beneficial effect that is not statistically significant, but provides evidence that hydroxychloroquine could work, we will proceed to a larger study with more patients (Phase III trial). However, if our study shows a large beneficial effect of hydroxychloroquine, similar to that seen in lupus patients, a larger trial would not be needed and hydroxychloroquine could become part of the standard treatment for ANCA vasculitis patients. This would represent a significant advance in the care of these patients. Given that hydroxychloroquine is a relatively inexpensive treatment, the overall cost to the health service could be reduced.