Combination Therapy for Atopic Dermatitis
Atopic dermatitis is a chronic relapsing disease with acute flares. The standard therapy is to treat acute flares using topical medications. The two most common classes of topical medications for atopic dermatitis (AD) are topical corticosteroids and topical calcineurin inhibitors.
Pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.
The hypothesis of this trial is that the combination of the two agents will lead to faster clearance than the single agent of topical corticosteroids.
|Atopic Dermatitis||Drug: Combination of pimecrolimus and fluticasone Drug: pimecrolimus||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||An Exploratory Double-blind, Randomized, Vehicle-controlled, Paired Study to Evaluate the Efficacy and Safety of Concomitant Use of Elidel Cream 1% and Cutivate Cream 0.05% in Patients With Severe Lesions of Atopic Dermatitis (AD)|
- Change From Baseline in the m-EASI (Eczema Area Severity Index) Score. [ Time Frame: up to 15 days ]
Eczema Area severity index (EASI) is a composition of scores based on area of eczema involved, (0 = mild to 3 = severe) for four separate Atopic Dermatitis (AD) symptoms: erythema,infiltration ⁄population, excoriation and ichenification.
Total score 0-12
- The Time to Clearance of the Disease [ Time Frame: assessed up to 30 days following drug application ]The time to clearance of eczema measured in days
- The Time to the First Day When m-EASI is Scored by the Investigator as 2 or Less [ Time Frame: up to one week ]Time to partial clearance of the localized eczema lesion assessed by the investigator is measured in days
- The Percentage of Target Areas Reaching a l-IGA (Localized Investigator Global Assessment (l-IGA) or 0 or 1) [ Time Frame: up to 15 days ]The Investigator Global Assessment (IGA) and l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe). The percentage of eczema lesions from the total population that reach almost clear
- The Percentage of Target Areas Improved (i.e., Decrease in Localized Investigator Global Assessmet (l-IGA) Score From Baseline) [ Time Frame: up to 15 days ]
The percentage of eczema areas that show improvement in l-IGA score.
The l-IGA were graded on a scale of 0-4 (0 = clear, 1 = almost clear, 2 = mild disease, 3 = moderate disease, 4 = severe disease).
- The Percentage of Target Areas Reaching a m-EASI (Modifed-Eczema Area Severity Index) Score of 2 or Less [ Time Frame: up to one week ]
The EASI is a measure of Atopic Dermatitis (AD) severity. A m-EASI score (0-12) was also calculated as the sum of severity (0 = mild to 3 = severe) for four separate AD symptoms: erythema, infiltration ⁄population, excoriation and lichenification.
The percentage of participants whose eczema reaches almost clear
- Change From Baseline in Patients' Self Assessment of Disease Severity (PSA) of Target Areas [ Time Frame: 30 days ]
The patient or caregiver assessment of eczema severity (PSA) was recorded daily in a diary using a 0-4 scale similar to that of the IGA.(0 = clear,
1 = almost clear, 2 = mild disease, 3 = moderate disease,4 = severe disease).
Difference in value of PSA from baseline to end of study
|Study Start Date:||October 2004|
|Study Completion Date:||June 2005|
|Primary Completion Date:||June 2005 (Final data collection date for primary outcome measure)|
Placebo Comparator: placebo
apply daily with fluticasone cream for flares
|Active Comparator: pimecrolimus cream||
Drug: Combination of pimecrolimus and fluticasone
Pimecrolimus cream twice a day and fluticasone cream once a day
Other Names:Drug: pimecrolimus
apply daily with fluticasone cream for flares
This trial is a double-blind controlled trial of fluticasone cream daily and pimecrolimus cream BID versus fluticasone cream daily and placebo cream BID for the treatment of acute flares of atopic dermatitis.
While pimecrolimus cream 1% has been proven to be effective in mild and moderate Atopic dermatitis (AD), there is a need for a fast control of severe skin lesions. On the other hand, reducing the duration of the topical corticosteroid treatment is a reasonable approach to minimize the occurrence of adverse effects.
Because pimecrolimus and topical corticosteroids exert their activity by different mechanisms, there may be a synergistic effect of the combination therapy. Therefore, a combination therapy may provide a faster resolution of severe skin lesions and consequently reduce the duration of the topical corticosteroid treatment. Another benefit of the combination therapy maybe the use of a lower potency corticosteroid to achieve the same degree of clearance.
In vitro data have demonstrated that a combination of steroids and tacrolimus has synergistic effects on in vitro human lymphocyte proliferation. In addition, it has previously been reported, in a pilot investigation in two subjects, that a combination regimen of pimecrolimus 1% twice a day and fluticasone propionate cream 0.05% once daily was superior to fluticasone propionate cream 0.05% once daily in the acute treatment of atopic dermatitis (AD).
This study is conducted to validate these findings in a larger number of patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00119158
|United States, Colorado|
|National Jewish Research Medical Center|
|Denver, Colorado, United States, 80206|
|United States, Illinois|
|Northwestern University School of Medicine|
|Chicago, Illinois, United States, 60611|
|United States, Texas|
|University of Texas at Houston Medical School|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jonathan M Spergel, MD, PhD||Children's Hospital of Philadelphia|