Levocetirizine Plus Bed-Time Hydroxyzine in the Management of Corticodependent Chronic Urticaria Versus Levocetirizine Alone in High Doses
Condition: Chronic Urticaria
MeSH terms: Urticaria; Chronic Urticaria
Study type: Interventional
Phase: Phase 4

Summary: 
      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: 
      Study design:

      The study will involve two distinct parts (flow chart):

        1. 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.

        2. 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.
    

Intervention name(s): Levocetirizine; Levocetirizine plus Hydroxyzine
Intervention type(s): Drug; Drug
Intervention description(s): 20 mg levocetirizine for 5 days; 24 patient will receive 15 mg Levocetirizine plus 50 mg Hydroxyzine at bad time for 5 days
Other intervention name(s): Xyzal; Xyzal plus Atarax
Intervention MeSH terms: Cetirizine; Hydroxyzine; Levocetirizine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Chronic urticaria; Urticaria; Antihistamine