Chronic Urticaria - Long Term Assessment of Effects of Rupatadine
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|ClinicalTrials.gov Identifier: NCT02358265|
Recruitment Status : Terminated (poor recruitment)
First Posted : February 6, 2015
Last Update Posted : September 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Chronic Urticaria||Drug: 10 mg Rupatadine on demand Drug: 10 mg Rupatadine Drug: 20 mg Rupatadine Drug: 10 mg Rupatadine on demand (sham updosing to 20 mg)||Phase 3|
The treatment of CSU with nsAHs is currently the most common and only licensed therapeutic option to reduce the patients' wheal and flare type skin reactions and pruritus. CSU is a highly fluctuating disease and the severity of symptoms can change markedly from day to day. This is one of the reasons why, in routine daily practice, many patients tend to perform an on demand rather than a continuous, daily, preventive treatment of their symptoms with nsAHs. While in the field of allergic rhinitis several studies point towards a better efficacy of nsAHs if continuously given (6-8), the only study in CSU comparing both treatment approaches was published by Grob and colleagues (9). They were able to demonstrate that continuous daily treatment with the nsAH desloratadine resulted in significantly better quality of life as compared to on demand therapy. While these studies indicate that the treatment schedule can generally have a major impact on the outcome of treatment, the results on the efficacy of on demand nsAHs in CSU remains to be confirmed independently.
In addition to the optimal treatment schedule, there is an ongoing discussion regarding the long-term outcome of nsAH treatment. While the mode of action of nsAHs suggests a pure symptomatic therapeutic effect, there have been speculations that a disease modification effect might also occur. Indeed, in 2010, a Japanese group (Kono et al.) presented data on the EADV meeting in Gothenburg demonstrating that continuous prophylactic antihistamine therapy of CSU patients with ebastine (a nsAH) for a period of three months was associated with a lower recurrence rate after discontinuation than the same treatment lasting for only one month, provided that the drug was effective and safe during early treatment. As of yet, these results also have to be confirmed independently.
Sufficient reduction of urticarial symptoms requires higher than the licensed dosing of antihistamines in many CSU patients (10-14). In fact, increasing the dose of nsAHs up to fourfold has been shown to be more effective as compared to the standard dose in different subforms of chronic urticaria (10, 11, 14). However, for some patients even high dosed nsAHs are not enough to effectively suppress disease symptoms (11-14). The exact reasons for this are still unknown. Probably, other mediators than histamine are also involved in the development of urticaria symptoms. One such other candidate mediator is platelet activating factor (PAF). PAF is a potent phospholipid mediator with various biological activities, including platelet aggregation, airway constriction, hypotension, and vascular permeation. PAF also mediates allergic reactions and has been claimed to contribute to the pathogenesis of urticaria. Intradermal PAF injection results in a pruritic wheal and flare reaction in subjects with and without allergies (15). PAF injection is followed by a dose-dependent histamine release in vivo (16) and in cold contact urticaria, there is evidence available that PAF is an additional important mediator associated with the inflammatory reaction in the skin (17, 18). Notably, Krause et al. could demonstrate that intradermal PAF injection results in a wheal and flare type skin reaction without inducing mast cell degranulation (19). PAF may, therefore, be a relevant mediator in the pathogenesis of urticaria that acts downstream of mast cell activation and is independent of H1-receptor activation.
Rupatadine, is a drug which possesses a potent antihistamine and PAF antagonistic activity and, recently, it has been demonstrated to be safe and effective in the treatment of chronic urticaria (3, 4) and cold contact urticaria (5). Notably, it has also been shown that an increased dose of 20 mg rupatadine is more effective in the treatment of CSU symptoms as compared to the licensed 10 mg dose (20).
In summary, it seems more than reasonable to use rupatadine as a study drug in patients with CSU in order to better characterize the best nsAH treatment schedule (continuous vs. on-demand), the long-term outcome of nsAH therapy and the influence of updosing on the latter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||192 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||A Multi-center, Randomized, Double Blind, Dose Escalating Phase III Study on the Efficacy, Safety and Long Term Outcome of Continuous vs. on Demand Treatment of Chronic Spontaneous Urticaria With Rupatadine.|
|Study Start Date :||December 2014|
|Actual Primary Completion Date :||November 20, 2017|
|Actual Study Completion Date :||June 15, 2018|
Active Comparator: 10 mg Rupatadine on demand
Rupatadine 10 mg, on demand
Drug: 10 mg Rupatadine on demand
Group A1 (dose administered: 10 mg rupatadine on demand): one tablet of placebo once daily- one on-demand tablet of rupatadine 10 mg intake only if needed.
Active Comparator: 10 mg Rupatadin
Rupatadine 10 mg, continuously
Drug: 10 mg Rupatadine
Group B1 (dose administered: 10 mg rupatadine continuously): one tablet of rupatadine 10 mg once daily, one on-demand tablet of placebo, intake only if needed.
Active Comparator: 20 mg Rupatadine
Rupatadine 20 mg, continuously
Drug: 20 mg Rupatadine
Group B2 (dose administered: 10 mg rupatadine continuously): two tablets of rupatadine 10 mg daily- one on-demand tablet of placebo , intake only if needed.
Active Comparator: 10 mg rupatadine on demand (sham upd.)
Rupatadine 10 mg, on demand (sham updosing to 20 mg)
Drug: 10 mg Rupatadine on demand (sham updosing to 20 mg)
Group A2 (dose administered: 10 mg rupatadine on demand): two tablets of placebo daily- one on-demand tablet of rupatadine 10 mg ,intake only if needed.
- Urticaria Activity Score (7 day cummulative score - UAS7) [ Time Frame: 1 week ]The UAS daily quantifies wheals (0-3 points) and itching (0-3 points). Accordingly, the minimum and maximum value of the 7 day cumulative score (UAS7) is 0 and 42, respectively.
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02358265
|Berlin, Germany, 10117|