Chronic UrticariaPhase 3NCT02358265
Chronic Urticaria - Long Term Assessment of Effects of Rupatadine
A Phase 3 study testing 10 mg Rupatadine on demand, 10 mg Rupatadine and 20 mg Rupatadine in people with Chronic Urticaria, run by Charite University, Berlin, Germany at 1 site in Germany.
Trial summary
To compare CSU disease activity at the end of the follow up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Chronic Urticaria
- What is being tested?
- 10 mg Rupatadine on demand, 10 mg Rupatadine and 20 mg Rupatadine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2014to 15 Jun 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged 18 years and older
- Documented history of active CSU (urticaria and wheals) with or without an associated angioedema for at least three days per week over the last 6 weeks prior to visit 1 (screening). Urticaria symptoms must comprise wheals and itch
- UAS7 of ≥6 during the screening phase
- Overall duration of chronic spontaneous urticaria for at least 3 months
- Informed consent signed and dated
- Able to read, understand and willing to sign the informed consent form and abide with study procedures
Show all 9Show fewer
- Willing, committed and able to return for all clinic visits and complete all study-related procedures
- In females of childbearing potential: negative pregnancy test; females willing to use highly effective contraception (Pearl-Index < 1) a woman will be considered not of childbearing potential if she is post-menopausal for > 2 years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
- No participation in other clinical trials 4 weeks before and after participation in this study
Who cannot join
- Chronic spontaneous urticaria patients with a known resistance to nsAH in 4 times the licensed doses
- Chronic spontaneous urticaria patients with a known resistance to rupatadine
- Isolated presence or domination of inducible forms of urticaria or cholinergic urticaria (no chronic spontaneous urticaria)
- History of adverse reactions to rupatadine or known hypersensitivity to rupatadine or its ingredients
- Intake of oral corticosteroids or intravenously applied corticosteroids within 28 days prior to screening visit
- Use of depot corticosteroids within 3 months prior to screening visit (inhaled corticosteroids are allowed)
Show all 25Show fewer
- Use of systemic immunosupressants/immunomodulators such as ciclosporin, dapsone, metotrexate, and comparable drugs within 28 days prior to screening visit.
- Significant medical condition, in the opinion of the Investigator, rendering the patient immunocompromised or not suitable for a clinical trial
- Significant concomitant illness, in the opinion of the Investigator, that would adversely affect the subject's participation or evaluation in this study
- Subjects for whom there is concern, in the opinion of the Investigator, about compliance with the protocol procedures
- The presence of a permanent gastrointestinal condition which may influence the oral therapy (chronic diarrhoea diseases, congenital malformations or surgical mutilations of gastrointestinal tract)
- Presence of active cancer which requires chemotherapy or radiation therapy
- History or presence of epilepsy, significant neurological disorders, cerebrovascular attacks or ischemia
- History or presence of myocardial infarction or acute myocardial ischemia
- History or presence of cardiac arrhythmia which requires drug therapy
- History or presence of clinically significant bradycardia (<50 bpm)
- ECG alterations of repolarisation (QTc prolongations >450ms in females, >430ms in males)
- Blood pressure >180/100 mmHg and/or heart rate >100/min
- Presence of uncorrected hypokalemia or hyperkalemia
- Evidence of significant hepatic or renal disease (GOT and/or GPT >2 times above the upper reference value, serum creatinine 1.5 times above the upper reference value)
- Presence of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
- Medication with HMG-CoA reductase inhibitors (statins)
- Presence of alcohol abuse or drug addiction
- Pregnancy or breast-feeding
- Subjects who are inmates of psychiatric wards, prisons, or other state institutions. Existing or planned placement in an institution after ruling according to § 40 passage 1, number 4 AMG (Arzneimittelgesetz).
Trial locations and contacts
1 site in 1 country.
About this study
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.
To compare CSU disease activity at the end of the follow up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase
Read the detailed description
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.
- Conditions
- Chronic Urticaria
- Being tested
- 10 mg Rupatadine on demand, 10 mg Rupatadine, 20 mg Rupatadine, 10 mg Rupatadine on demand (sham updosing to 20 mg)
- Medical subject headings
- Chronic Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg Rupatadine on demandDrug
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.
10 mg RupatadineDrug
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.
20 mg RupatadineDrug
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.
10 mg Rupatadine on demand (sham updosing to 20 mg)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 10 mg Rupatadine on demand | Active comparator | Rupatadine 10 mg, on demand Receives: Drug: 10 mg Rupatadine on demand |
| 10 mg Rupatadin | Active comparator | Rupatadine 10 mg, continuously Receives: Drug: 10 mg Rupatadine |
| 20 mg Rupatadine | Active comparator | Rupatadine 20 mg, continuously Receives: Drug: 20 mg Rupatadine |
| 10 mg rupatadine on demand (sham upd.) | Active comparator | Rupatadine 10 mg, on demand (sham updosing to 20 mg) Receives: Drug: 10 mg Rupatadine on demand (sham updosing to 20 mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urticaria Activity Score (7 day cummulative score - UAS7)
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.
Measured: 1 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2015 (estimated)
- Study startDec 2014
- Primary completion20 Nov 2017
- Study completion15 Jun 2018
Why it stopped: poor recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic UrticariaStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, K. Weller, Charite University, Berlin, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02358265
- Sponsor's protocol ID
- CU-LATER
- Status last verified
- Sep 2019
- First submitted
- 18 Dec 2014
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02358265
- Acronym / sponsor ID
- CU-LATER
- Conditions
- Chronic Urticaria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor recruitment
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Dec 2014
- Primary completion
- 20 Nov 2017 (actual)
- Study completion
- 15 Jun 2018 (actual)
- First posted
- 6 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To compare CSU disease activity at the end of the follow up phase between patients that had been treated daily continuously vs. on-demand in the treatment phase
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 10 mg Rupatadine on demand | Active comparator | Drug: 10 mg Rupatadine on demandRupatadine 10 mg, on demand |
| 10 mg Rupatadin | Active comparator | Drug: 10 mg RupatadineRupatadine 10 mg, continuously |
| 20 mg Rupatadine | Active comparator | Drug: 20 mg RupatadineRupatadine 20 mg, continuously |
| 10 mg rupatadine on demand (sham upd.) | Active comparator | Drug: 10 mg Rupatadine on demand (sham updosing to 20 mg)Rupatadine 10 mg, on demand (sham updosing to 20 mg) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female aged 18 years and older
- Documented history of active CSU (urticaria and wheals) with or without an associated angioedema for at least three days per week over the last 6 weeks prior to visit 1 (screening). Urticaria symptoms must comprise wheals and itch
- UAS7 of ≥6 during the screening phase
- Overall duration of chronic spontaneous urticaria for at least 3 months
- Informed consent signed and dated
Key exclusion criteria (25 listed)
- Chronic spontaneous urticaria patients with a known resistance to nsAH in 4 times the licensed doses
- Chronic spontaneous urticaria patients with a known resistance to rupatadine
- Isolated presence or domination of inducible forms of urticaria or cholinergic urticaria (no chronic spontaneous urticaria)
- History of adverse reactions to rupatadine or known hypersensitivity to rupatadine or its ingredients
- Intake of oral corticosteroids or intravenously applied corticosteroids within 28 days prior to screening visit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 10 mg Rupatadine on demandGroup 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. | Drug | 10 mg Rupatadine on demand |
| 10 mg RupatadineGroup 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. | Drug | 10 mg Rupatadin |
| 20 mg RupatadineGroup B2 (dose administered: 10 mg rupatadine continuously): two tablets of rupatadine 10 mg daily- one on-demand tablet of placebo , intake only if needed. | Drug | 20 mg Rupatadine |
| 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. | Drug | 10 mg rupatadine on demand (sham upd.) |
Primary outcome
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.
Results and safety
The study was stopped early (reason given: poor recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
Related trials for Chronic Urticaria
Not yet recruitingObservational study
Remibrutinib in Real-world Clinical Practice - a South Korea Sub-Study
Chronic Spontaneous Urticaria
RecruitingPhase 3
A Study to Investigate Efficacy, Safety and Tolerability of Barzolvolimab Versus Placebo in Adults With Cold Induced Urticaria and Symptomatic Dermographism Inadequately Controlled by H1-antihistamines (EMBARQ - ColdU and SD)
Chronic Inducible Urticaria, Cold Urticaria
Enrolling by invitationPhase 3
Long-term Efficacy and Safety Extension (LTE) Study of Barzolvolimab in Participants With Chronic Spontaneous Urticaria
Chronic Spontaneous Urticaria
RecruitingPhase 2
A Study to Assess the Efficacy and Safety of THB335 in Adults With Chronic Spontaneous Urticaria (CSU)
Chronic Spontaneous Urticaria (CSU), Chronic Idiopathic Urticaria
RecruitingPhase 1
A Phase 1 Study of GTX-B001 in Healthy Subjects and Patients With Chronic Inducible Urticaria
Healthy Subjects, Cold Urticaria
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 10 mg Rupatadine on demand, 10 mg Rupatadine and 20 mg Rupatadine in people with Chronic Urticaria, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urticaria Activity Score (7 day cummulative score - UAS7) (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.