Treatments Comparison for Skin Vasculitis
(ARAMIS Trial)
Recruiting in Palo Alto (17 mi)
+7 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Pennsylvania
Disqualifiers: Systemic vasculitis, Auto-immune conditions, Cancer, Infections, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing three different drugs to find the best treatment for patients with isolated skin vasculitis. The drugs help by reducing inflammation and controlling the immune system.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop all current medications, but if you are taking prednisone for skin vasculitis, you will need to stop it within 6 weeks after starting the study drug, following a specific tapering schedule. If you are on a low and stable dose of glucocorticoids for other conditions, you can continue that dose during the study.
What data supports the effectiveness of the drug for treating skin vasculitis?
Research shows that Dapsone, a component of the treatment, has been effective in treating severe skin vasculitis and other inflammatory skin conditions, leading to remission in some cases. Additionally, Colchicine has been beneficial in managing prolonged skin symptoms in vasculitis, particularly in cases resistant to other treatments.12345
Is the treatment generally safe for humans?
Dapsone has been used safely in humans for various skin conditions, showing anti-inflammatory effects without increasing side effects when combined with other treatments. Azathioprine, however, may have more side effects compared to alternatives like mycophenolate mofetil, which is considered safer.12678
How does the drug combination of Azathioprine, Colchicine, and Dapsone differ from other treatments for skin vasculitis?
This drug combination is unique because it combines Azathioprine, known for its safety in treating various skin conditions, with Colchicine and Dapsone, which are effective for chronic or relapsing skin vasculitis and urticarial vasculitis. Dapsone, in particular, has shown success in treating severe and chronic vasculitic ulcerations where other immunosuppressants have failed.124910
Eligibility Criteria
Adults with isolated skin vasculitis, confirmed by biopsy, lasting at least 1 month or having multiple flares. Eligible participants have primary skin vasculitis without serious extra-skin symptoms and may have used steroids before joining. Excluded are those with contraindications to the study drugs, systemic vasculitis signs, active cancer in the last 5 years, severe infections or organ insufficiency.Inclusion Criteria
I am 18 years old or older.
I have a specific type of skin vasculitis without kidney problems.
I have a skin condition without serious effects on other body parts.
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Exclusion Criteria
I cannot take or have not responded to two or three of the drugs in this study.
I have a G6PD deficiency or a history of hemolytic anemia.
My kidneys are not working well, with a creatinine clearance below 60 mL/min.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment Stage 1
Participants are randomized to receive one of three medications (colchicine, dapsone, or azathioprine) for 6 months
6 months
Visits at months 1, 3, and 6
Follow-up
Participants are monitored for response to treatment and side effects
6 months
Visits at months 9 and 12
Treatment Stage 2
Participants who discontinue the initial treatment are re-randomized to receive one of the remaining two medications for another 6 months
6 months
Visits at months 1, 3, and 6 of stage 2
Treatment Details
Interventions
- Azathioprine (Immunosuppressant)
- Colchicine (Anti-inflammatory agent)
- Dapsone (Anti-inflammatory agent)
Trial OverviewThe trial is testing three treatments for skin vasculitis: Colchicine, Dapsone, and Azathioprine. It's a multi-center study where patients are randomly assigned to receive one of these standard care options to compare their effectiveness.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Stage 2Experimental Treatment3 Interventions
If the patient has to discontinue the study drug within the (stage 1) 6 month study period or during the subsequent follow-up period (up to month 12) because of a lack of response (or failure), flare or side effect, he/she will be randomized again to receive one of the remaining two study drugs (stage 2, with a 1:1 randomization ratio, colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint in this second stage will again be the response to treatment at 6 months.
Group II: Stage 1Experimental Treatment3 Interventions
Eligible patients will be initially randomized (1:1:1) to receive one of the 3 medications under investigation (colchicine 0.6 mg x 2/day; dapsone 150 mg/day; azathioprine 2 mg/kg/day) for 6 months. Endpoint is response to treatment at month 6 (stage 1).
Azathioprine is already approved in European Union, United States, Canada for the following indications:
🇪🇺 Approved in European Union as Imuran for:
- Prevention of rejection in organ transplantation
- Treatment of autoimmune diseases such as rheumatoid arthritis
🇺🇸 Approved in United States as Imuran for:
- Prevention of rejection in organ transplantation
- Treatment of rheumatoid arthritis
🇨🇦 Approved in Canada as Imuran for:
- Prevention of rejection in organ transplantation
- Treatment of rheumatoid arthritis
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Vanderbilt UniversityNashville, TN
University of Toronto Mount Sinai HospitalToronto, Canada
University of Kansas Medical CenterKansas City, KS
UT Southwestern Medical CenterDallas, TX
More Trial Locations
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Who Is Running the Clinical Trial?
University of PennsylvaniaLead Sponsor
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Collaborator
Office of Rare Diseases (ORD)Collaborator
National Center for Advancing Translational Sciences (NCATS)Collaborator
References
[Refractory cutaneous necrotizing vasculitis. Successful sulfone therapy]. [2018]The clinical picture in vasculitis varies from few self-limiting symptoms to life-threatening illnesses affecting multiple organs. We describe the course of a woman patient who had had a severe cutaneous necrotizing vasculitis for more than 10 years. Various immunsuppressants, including cyclophosphamide, had failed to improve the clinical course, although adequate doses were given for a sufficient period. Treatment with DADPS (diaminodiphenylsulfone, dapsone), however, finally led to complete remission of the severe and chronic vasculitic ulcerations. Indications for DADPS treatment of inflammatory cutaneous diseases are discussed, and an overview of cutaneous vasculitis is provided.
Cutaneous involvement of dermatomyositis can respond to Dapsone therapy. [2019]Dapsone (4,4-diaminodiphenylsulfone) is a sulfone antibiotic used in the treatment of leprosy, but dermatologists more commonly utilize its anti-inflammatory properties particularly directed against leukocytes to treat various bullous disorders, erythema nodosum, pyoderma gangrenosum, Sweet's syndrome, cutaneous vasculitis, and cutaneous forms of lupus erythematosus. The cutaneous manifestations of dermatomyositis are often resistant to antimalarial and immunosuppressive therapies.
Successful treatment of IgA vasculitis with prolonged cutaneous manifestation with colchicine in a 10-year-old boy. [2022]We report a 10-year-old boy with immunoglobulin (Ig)A vasculitis (IgAV) with prolonged cutaneous manifestations who was successfully treated with colchicine. At the age of 9 years, he was diagnosed as having IgAV by typical purpura, abdominal pain, and haematochezia. Initially, his severe gastrointestinal manifestation subsided by prednisolone 60 mg/day and intravenous methylprednisolone pulse therapy. However, his gastrointestinal manifestation was glucocorticoid-dependent and refractory to factor XIII concentrate, intravenous IgG, and mycophenolate mofetil. His abdominal pain and haematochezia responded to the combination therapy with dapsone and low dose of prednisolone 5 mg/day and did not relapse even after discontinuation of dapsone. On the other hand, the effect of dapsone on his cutaneous manifestation was dose-dependent as well as dapsone had no glucocorticoid-sparing effect. Approximately 12 months after onset, colchicine treatment was started, which resulted in remission of his chronic cutaneous manifestation. After prednisolone was tapered off, his cutaneous manifestation is currently well-controlled on colchicine 0.5 mg/day without adverse events. He had never complicated kidney involvements. In conclusion, it is observed that colchicine treatment exerts a beneficial effect in IgAV patients with prolonged cutaneous manifestation refractory to multiple drugs.
[Therapy of vasculitides and vasculopathies]. [2021]Treatment and course of leukocytoclastic immune-complex vasculitis (LcV) depend on absence or presence of IgA in immune complexes [Henoch-Schoenlein-Purpura (PSH)]. LcV due to IgG- or IgM-containing immune complexes has a better prognosis. If triggers cannot be detected or avoided, symptomatic treatments are usually sufficient due to a usually favourable course. When hemorrhagic blisters suggest incipient skin necrosis corticosteroids are indicated. For chronic or relapsing LcV we suggest colchicine or dapsone. In adults with PSH and severe glomerulonephritis there is insufficient evidence for the efficacy of glucocorticoids; but e.g. ACE inhibitors can be helpful depending on symptoms. In cryoglobulinemic vasculitis underlying diseases (often plasmocytoma or hepatitis C) should be treated, sometimes supplemented by plasmapheresis. Dapsone or colchicine are usually started for urticarial vasculitis. ANCA-associated systemic vasculitis requires rapid and aggressive induction therapy, usually with glucocorticoids and cyclophosphamide. In classic polyarteriitis nodosa glucocorticoids improve prognosis, in polyarteriitis nodosa cutanea colchicine or dapsone are more appropriate. Giant cell arteriitis requires rapid therapy with glucocorticoids. For livedo vasculopathy antithrombotic measures are required with low molecular heparin or antagonists to vitamin K, for maintenance dipyridamol und aspirin.
[Dapsone for chronic skin lesions in 3 children suffering from Henoch-Schönlein vasculitis]. [2021]We describe 3 cases of chronic purpuric skin lesions in children suffering from systemic vasculitis: 3 children with Henoch-Schönlein purpura. Dapsone was introduced when skin lesions were recurrent, extensive, and persistent, due to its known ability to act as an anti-IgA and as an anticytotoxic agent against polynuclear neutrophils. Fast and complete but purely suspensive healing of skin lesions was noted. One child developed methemoglobinemia, a known side-effect of dapsone, highlighting the need for adequate prescription and follow-up.
Use of cyclophosphamide in azathioprine failures in pemphigus. [2019]Four patients with pemphigus vulgaris are presented in which diagnosis was confirmed histologically and immunopathologically. Although these patients responded to high-dose prednisone therapy during the initial stages of acute disease, the addition of azathioprine failed to allow lower steroid doses and did not result in prolonged, complete remission. Indeed, the disease was exacerbated during azathioprine therapy, and significant side effects from prolonged high-dose steroid therapy were observed. Both clinical and serologic remission resulted from the addition of cyclophosphamide and dapsone to prednisone therapy. Thus, when azathioprine fails to produce remission or a steroid-sparing effect, cyclophosphamide may be an effective alternative. During a prolonged follow-up period, no recurrences of pemphigus have been observed, and no significant side effects of cyclophosphamide (Cytoxan) have been encountered. The addition of dapsone produced enhanced anti-inflammatory effects without increasing the existing or potential side effects of steroid therapy. Dapsone was easily withdrawn at the onset of remission. Thus the anti-inflammatory effect of dapsone may prove valuable in patients for whom steroids are contraindicated, who develop significant side effects during long-term steroid therapy, or for whom increases of dose threaten to enhance the possibility of catastrophic side effects.
Immunosuppressive therapy for autoimmune bullous diseases. [2021]Adjuvant immunosuppressive drugs are widely used to minimize corticosteroid-related adverse effects in the short-term and long-term management of cautoimmune bullous diseases. In bullous pemphigoid and pemphigus vulgaris, azathioprine and mycophenolate mofetil seem to be equally effective when used in combination with oral corticosteroids, but mycophenolate mofetil is less myelosuppressive and hepatotoxic. Due to a better safety profile, mycophenolate mofetil or enteric-coated mycophenolate sodium may gradually replace azathioprine as the first-line adjuvant of choice in the treatment of moderate to severe autoimmune bullous diseases, including epidermolysis bullosa acquisita and cicatricial pemphigoid. Cyclophosphamide still has a place in the treatment of severe relapsing autoimmune bullous diseases. Continuous oral cyclophosphamide provides optimal immunosuppression, but it also produces the highest cumulative dose. Several pulsed cyclophosphamide regimens have, therefore, been developed and are reported to be effective in severe forms of pemphigus. Randomized controlled studies are needed to compare the efficacy and safety of cyclophosphamide with newer treatment options, such as rituximab and immunoapheresis, and to define optimal dose ranges and duration of available immunosuppressive treatments in different stages of autoimmune bullous diseases.
[Urticaria vasculitis and sulfone, a case report]. [2013]Systemic corticosteroids play a predominant role in the treatment of urticarial vasculitis (U.V.). If steroids are contraindicated, there may be applied a variety of pharmacologically different compounds. A female patient suffering from U.V. and metabolic syndrome, who had not shown any positive response to indomethacin, H1 and H2 antagonists, or colchicine, was treated with dapsone. As a result, the clinical symptoms improved within a few days and her hypocomplementemia normalized. We discuss the possible mechanisms of action of sulphones in U.V.
Immunosuppressive agents in dermatology. [2013]Azathioprine, cyclophosphamide, and cyclosporine are immunosuppressive agents commonly used by dermatologists. Azathioprine has a good safety profile and is preferred by most dermatologists for the treatment of bullous pemphigoid, cutaneous vasculitides, chronic eczematous dermatitides, and cutaneous manifestations of connective tissue diseases. For more fulminant diseases such as Wegener's granulomatosis, lymphomatoid granulomatosis, severe cases of systemic lupus erythematosus, or pemphigus, cyclophosphamide is more effective and its use is justified even though it is more toxic. Cyclosporine has been shown to be effective in a variety of dermatoses; the most promising results are seen in psoriasis, lichen planus, pyoderma gangrenosum, and chronic eczematous dermatitides. The long-term safety of cyclosporine remains to be determined, and it should be used judiciously with careful evaluation of the risk-benefit ratio in each case. Dermatologists who use immunosuppressive agents should be familiar with their indications, side effects, dosage, and monitoring.
Resistant discoid lupus erythematosus of palms and soles: successful treatment with azathioprine. [2019]We present the case of two patients with an unusual form of discoid lupus erythematosus that was confined almost exclusively to the palms and soles. In both patients this form of discoid lupus erythematosus did not respond to conventional therapies, which included topical steroids, intralesional steroids, prednisone, quinacrine hydrochloride, hydroxychloroquine sulfate, colchicine, and dapsone. Both patients were then treated with azathioprine. One patient dramatically improved with azathioprine, worsened each time the azathioprine was stopped or reduced, and responded again to the reinstitution of therapy. The other patient began taking azathioprine 8 months ago and has also experienced relief of her symptoms. These cases suggest that discoid lupus erythematosus principally involving the palms and soles is difficult to treat with conventional medication and that azathioprine, which appears to be useful, should be tried after the failure of other therapies.