Levocetirizine Plus Bed-Time Hydroxyzine in the Management of Corticodependent Chronic Urticaria Versus Levocetirizine Alone in High Doses

Study Overview
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Brief Summary
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Allen Kaplan is a prominent American allergist with the reputation of leader in the field of chronic urticaria. He advocates treatment with first generation hydroxyzine, which he considers at least as effective as modern second generation H1-blockers in suppressing the symptoms of difficult-to-treat / systemic-steroid-dependant cases of chronic urticaria. He further speculates that hydroxyzine may have the advantage to better suppress itch and improve nighttime sleep. This has prompted many practitioners around the world to believe that adding hydroxyzine to the treatment regimen at bed time at night may be beneficial to patients. At the same time European guidelines indicate modern second generation H1-blockers in higher than conventional doses as drugs of choice for such cases. However, there is no evidence from clinical trials addressing this controversy. The investigators' previous studies suggest that levocetirizine at quadruple doses may be beneficial in difficult to treat urticaria by reducing lesions and itch, improving quality of life and night time sleep, while not causing day time somnolence. First generation H1-receptor antagonists and hydroxyzine among them are known to penetrate the blood / brain barrier and to cause sedation. The question stays whether this sedation is beneficial to the subjects with chronic urticaria at night, whether it has any hang-over unwanted effects the following day and whether this has any influence on the overall urticaria-specific quality of life.

Detailed Description
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Study design: The study will involve two distinct parts (flow chart): In-hospital assessment of effectiveness and tolerability of 10 & 20 mg levocetirizine vs. 100 & 200 mg hydroxyzine in subjects to be weaned off corticosteroid treatment. Subsequent ambulatory treatment of the same patients with 20 mg levocetirizine alone and 15 mg levocetirizine + 50 hydroxyzine at night Protocol description Patients with chronic urticaria treated with systemic steroids are traditionally admitted to the Clinic of Allergy and Asthma in Sofia to try to wean them off this class of drugs. Hospitalized patients will be invited to take part in the study and will sign an informed consent. They will be assessed by standard questionnaire and by objective assessment of the urticarial lesions, QoLQ will be filled in, discomfort due to urticaria, day time somnolence and night time sleep quality will be assessed on a visual analogue scale. Systemic steroids will be withheld and patients would be given 10 mg levocetirizine on Days 1 & 2; after a new assessment of quality of night time sleep and day time somnolence, 100 mg hydroxyzine will be given on Days 3 & 4. The cycle will be repeated on Days 5 & 6 and Days 7 & 8 with 20 mg levocetirizine and 200 hydroxyzine respectively. At this point patients will be discharged and randomized to two treatment arms: levocetirizine 20 mg per day and levocetirizine 15 mg + hydroxyzine 50 mg as evening dose for 5 days. Diaries will be given to patients for assessment of daily SS, day time somnolence score, quality of night time sleep, facial tissue swelling, rescue medication with oral prednisolone, adverse events, intake of any other medications. After 5 days the patients from arm 1 and 2 will be crossed over to the alternative treatment. QoLQ questionnaire will be filled out at onset, at cross over (day 5) and at the end of the 10 day treatment period. On completion of the study subjects will be asked to state there preference for one treatment or the other.

Official Title
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Efficacy and Safety of 20 mg Levocetirizine and 15 mg Levocetirizine + 50 mg Bed-Time Hydroxyzine in Severe Chronic Urticaria in Adults: a Pilot, Randomized, Double-blind, Cross-over and Parallel, Active-controlled, Single-centre Study

Conditions
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Chronic Urticaria

Intervention / Treatment
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* Drug: Levocetirizine
* Drug: Levocetirizine plus Hydroxyzine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 24 randomized patients of either sex, ≥18 years of age. Included patients should have at least a 6-week documented history of urticaria with intake of 15-30 mg Prednisolon. Exclusion Criteria: Patients with physically induced urticarias; pregnancy and lactation; any chronic disease requiring daily other drug treatment including, antihypertensives, antipsychotics and antidepressants; other skin disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levocetirizine<br>24 patients will received 20 mg Levocetirizine daily | Drug: Levocetirizine<br>* 20 mg levocetirizine for 5 days<br>* Other names: Xyzal;|
| Experimental: Levocetirizine plus Hydroxyzine<br>24 patient will receive 15 mg Levocetirizine plus 50 mg Hydroxyzine at bad time for 5 days | Drug: Levocetirizine plus Hydroxyzine<br>* 24 patient will receive 15 mg Levocetirizine plus 50 mg Hydroxyzine at bad time for 5 days<br>* Other names: Xyzal plus Atarax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urticaria specific quality of life | The primary objective of the study is to compare the effect on urticaria specific quality of life of two regimens: levocetirizine 20 mg per day (4x1 tablets) vs. levocetirizine 15 mg (3x1 tablets) + hydroxyzine 50 mg (2 tablets) before night time sleep. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of the two regimens on urticaria symptoms | To compare the effect of the two regimens on urticaria symptoms (number of wheals, pruritus severity | 1 year | 
| Effect on night time sleep | To compare the effect of the two regimens on the quality of night time sleep | 1 year | 
| Effect on day time somnolence | To compare the effect of the two regimens on the day time somnolence. | 1 year | 
| The effect on blood eosinophil numbers, Na+, K+, ALAT, ASAT, ECG | To document the effect of treatment with higher doses of levocetirizine or hydroxyzine on blood eosinophil numbers, Na+(sodium ion), K+(potassium ion), ALAT (Alanine transaminase), AST (Aspartate transaminase), ECG (Electrocardiogram) | 1 year | 
| To assess adverse events | To investigate safety by assessing the nature, incidence and severity of adverse events within the treatment groups | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic urticaria, Urticaria, Antihistamine