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

Condition(s) targeted: Chronic Urticaria

Intervention: Levocetirizine (Drug); Hydroxyzine (Drug); Levocetirizine plus Hydroxyzine (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Association Asthma, Bulgaria

Official(s) and/or principal investigator(s):
Todor A Popov, MD, PhD, Principal Investigator, Affiliation: Professor of Allergology

Overall contact:
Maria T Staevska, MD, Phone: +359898201927, Email: mari66sta@gmail.com

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.

Official title: Efficacy and Safety of 20 mg Levocetirizine, 200 mg Hydroxyzine 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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: Urticaria specific quality of life

Secondary outcome:

Effect of the three regimens on urticaria symptoms

Effect on night time sleep

Effect on day time somnolence

The effect on blood eosinophil numbers, Na+, K+, ALAT, ASAT, ECG

To assess adverse events

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, 15 mg levocetirizine + 50 hydroxyzine or hydroxyzine 200 mg.

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 three treatment arms: levocetirizine 20 mg per day, levocetirizine 15 mg + hydroxyzine 50 mg as evening dose and hydroxyzine 200 mg 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 while the patient from arm 3 will continue on hydroxyzine 200 mg for other 5 days. 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.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 40 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

Maria T Staevska, MD, Phone: +359898201927, Email: mari66sta@gmail.com

Medical University Sofia, Department of Allergology, Sofia 1431, Bulgaria; Recruiting
Vasil D Dimitrov, MD, PhD, Phone: +359888474728, Email: vasdim48@gmail.com
Todor A Popov, MD, PhD, Principal Investigator
Maria T Staevska, MD, Sub-Investigator
Tzvetelina L Canova, MD, Sub-Investigator
Tanja Z Kralimarkova, MD, Sub-Investigator
Vasil D Dimitrov, MD, PhD, Sub-Investigator

Related publications:

Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol. 2004 Sep;114(3):465-74; quiz 475. Review.

Kaplan AP. What the first 10,000 patients with chronic urticaria have taught me: a personal journey. J Allergy Clin Immunol. 2009 Mar;123(3):713-7. Epub 2008 Dec 10. No abstract available.

The effectiveness of levocetirizine and desloratadine in up to 4 times conventional doses in difficult-to-treat urticaria Staevska M, Popov T, Kralimarkova T, Lazarova C, Kraeva S, Popova D, Church D, Dimitrov V, Church M J Allergy Clin Immunol 2010;125:676-82

Starting date: March 2011
Last updated: June 21, 2011