| Author Year Country Quality score | Study design Setting | Population Eligibility criteria | Exclusion criteria | Age Gender Race/ethnicity | Interventions | Allowed other medications/interventions | Method of outcome assessment and timing of assessment | Number withdrawn/lost to fu/analyzed | Results |
|---|---|---|---|---|---|---|---|---|---|
| Head-to-head trials | |||||||||
| Garg 2007 India | Observational - single center | CIU Those showing complete symptomatic control of CIU at 6 weeks with cetirizine were shifted to an equivalent dose of 5 mg of levocetirizine and were assessed weekly | NA | Age range 15–65 years 60% male Ethnicity NR | Cetirizine 10 mg then levocetirizine 5 mg Studied sequentially for 6 weeks each | NR | Weekly assessment of wheal, flare and itch responses on a visual analog scale of 0–3 (0 -asymptomatic, 1 -mild, 2 - moderate, 3 - maximum severity) | 20/NR/30 | Cetirizine vs. levocetirizine Wheal response 30 vs. 28 Flare response 30 vs. 30 Itch response 30 vs. 9 |
| Guerra 1994 Italy | RCT, DB, Parallel-group | CIU Above the age of 12 years. | The exclusion criteria ere pregnancy or breast- feeding, steroid dependency, urticaria due to physical agents or angioneurotic oedema, idiosyncratic reaction to antihistamine drugs and multiple drug allergies. | Age: 38.8 years 61% female | L: loratadine 10 mg C: cetirizine 10 mg P: placebo | NR | Pts recorded in daily diaries. Pts were seen 3, 7, 14, and 28 days after the start of treatment when evaluations were made of clinical symptoms (a 4-point scale being used to evaluate pruritus, erythema, lesion type and size of largest lesion), the interference of the disease in the pts daily activities, therapeutic results and any side effects, and patients compliance with protocol. | 1/NR/unclear | TSS: A vs B: significant p<0.01 days 3,14,28 Day 3/7/14/28 (*estimated from figure): L:: −23%/−46%/−65%/−81% C: −35%/−50%/−60%/−69% P: −19%/−23%/−34%/−55% Active treatment significant vs. P, p<0.05 Responders: L asymptomatic vs. C: 63% vs 45%, NSD; P was significantly worse at 13% (p< 0.05) |
| Handa 2004 India Fair | Randomized, DB Setting NR | CIU Patients with CIU (urticaria wheals for ≥2d/w for 6 consecutive weeks before study entry) aged 17–65 years. Itching had to be moderate and hives present. | Patients suffering from other forms of urticaria and dermographisms as a primary diagnosis; pregnancy and lactation | Mean age: NR Gender: NR Ethnicity: NR | C: Cetirizine 10 mg qd F: Fexofenadine 180 mg qd 28-day treatment period | No other topical or systemic medication for CIU was allowed. | Assessments on days 14, 28; analog rating patient’s symptoms (0=none, 3=severe, very annoying, disturbing sleep or daily activities) | 19/0/97 | Symptom-free at endpoint: C: 27(51.9%) vs F: 2(4.4%) (p NR) Partial improvement at endpoint: C: 19(36.5%) vs F: 19(42.2%) (no p-value) No improvement at endpoint: C: 6(11.5%) vs F: 24(53.3%) (p-value NR) Complaints of increase in intensity of itching, wheals: At night: 35(36.1%) vs Daytime: 51(52.6%) |
| Thomas 1998 India | Randomized investigator-blinded parallel group, multicenter | 12 to 60 years suffering from urticaria for at least 6 weeks | History of asthma, other systemic conditions that could interfere with the study, multiple drug allergies, known non-response to antihistamines, patients suffering from pressure urticaria or cold urticaria and women who were pregnant, nursing or using birth control pills; antihistamines for 72 hours, systemic corticosteroids for 1 month, topical steroids for 2 weeks, cromolyn for 2 weeks and decongestants for one day preceding the trial. | NR, article states, “The two groups were similar in sex, age and weight” | Loratadine vs. cetirizine | NR but see excusions | Physicians and portents evaluated the number of lesions and episodes, the average size and duration of lesions, and the degree of pruritus on a 4 point scale at baseline and days 3, 7, 14 and 27 | 8/8/202 | Data reported in graphs Loratadine vs. cetirizine The number, size and the duration of lesions P < 0.05 Fall in the mean score of pruritus P < 0.05 All favored loratadine |
| Placebo-controlled trials | |||||||||
| Grob 2008 France | DB, RCT, multicentre (40) | CIU 18 years of age, history of CIU (i.e. pruritus and weals lasting 6 weeks; in good general health. CIU symptoms present for 3 weeks, with weals present for 3 days a week and a flare-up before visit 1 (previously untreated patients) or after discontinuation of prior treatment and completion of a drug-specific washout eriod, pruritus score of 2 (at least moderate pruritus), a weal score of 1 (at least 1–6 weals) and a global CIU severity score of 2 (at least moderate severity) at screening and baseline, also required to show an am/pm reflective pruritus score of 14 for the three consecutive days prior to baseline and the morning of day 1. | Pregnant or nursing, or expected to become pregnant during the study; had asthma requiring chronic inhaled or systemic corticosteroids; had been injected with corticosteroids within 90 days; had been hospitalized for CIU for 3 months ; had antihistamineresistant CIU; or had skin reactions due to drug-or foodrelated allergies; hypersensitivity to desloratadine or any of its excipients, clinically significant conditions that might interfere with the evaluation of CIU or compromise safety and the presence of affective or intellectual disorders that might invalidate informed consent or impede cooperation with study procedures. Treatment with other experimental medications was forbidden for 30 days or for 90 days in the case of experimental antibodies for asthma or allergic rhinitis. | mean age 41 yrs 39% male Ethnicity NR | Desloratadine 5 mg vs. placebo 6 weeks | see exclusions | DLQI and Total VQ-Dermato scores (range from 0 (least serious effect) to 112 (worst effect)) at visit 2 (baseline) and visit 5 (day 42) Daily patient diary of sleep disruption and disruption of daily activities | 57/1/137 | Desloratadine vs. placebo Change from baseline DLQI (SD) −6(6.2) vs. −2.2 (5.1) P < 0.001 VQ-Dermato (SD) −15.0 (17.7) vs. −8.0 (18.8) P = 0.035 VQ-Dermato domain scores at day 42 Daily activities 18.1 vs. 32.6 P = 0.001 Mood 7.5 vs. 14.7 P = 0.027 Social life 10 vs. 21 P = 0.005 Physical pain 42.3 vs. 58.2 P = 0.006 Self-image 21.5 vs. 30 P = NS Leisure activities 19.7 vs. 26.2 P = NS Limitations due to treatment 3.1 vs. 12.9 P = NS |
| Kaplan 2005 USA Fair | RCT, DB, parallel-group Multicenter | CIU Patients aged >12 years, diagnosed with active CIU, with a history of >3 wheals weekly for 6 consecutive weeks and rating of pruritus within last 12 months as at least moderately severe. | Pregnancy and lactation, women without reliable medical or barrier contraception, mental illness, malnutrition, blood dyscrasia, renal of hepatic insufficiency, chronic infection, drug/alcohol abuse, malignancy, malabsorption, history of hypersensitivity/unresponsiveness to study drug or similar drugs, treatment with any investigational product in prior 30 days, serious cardiovascular hepatic, endocrine or other major systematic disease | 97% aged <65 years 26% male White: 72% Black: 11% Asian/Oriental: 4% Other: 14% | F: Fexofenadine 180 mg qd P: Placebo qd 28-day treatment period | NR/NR | Patient diary was completed bid, recording symptoms and adverse events. Weekly visits to collect data; safety assessments taken at baseline and endpoint. Primary outcome was change from baseline in mean daily number of wheals and the mean daily severity or pruritis score over 28d (rated 0–4, 0=none, 4=very severe). Secondary outcomes were patients assessment of the number, frequency, size, duration of lesions, and the severity of pruritis, each assessed 0–3 scale. Modified TSS was the sum of these 5 scores, calculated bid. Patient and investigator independent global evaluations of overall efficacy of treatment on (scale 0=no improvement or worsening, 4=complete disappearance of symptoms). | Withdrawals: F 7%, P 14%/NR/259 | Mean daily number of wheals: F −0.78, P −0.4, p<.001 Change from baseline in mean pruritis score (0–4): F −1.04, P − 0.57, p<.001 Mean reductions in TSS daily scores F>P, p<.001 Global evaluations, both by patient and investigator: F>P, p<0.001 |
| Kapp 2006 Germany and Switzerland | randomized, double-blind, placebo-controlled, parallel, multicenter study (19) | CIU CIU, i.e. episodes of hives of characteristic wheal and flare appearance, occurring regularly, at least three times a week for a period of at least 6 weeks during the previous could have interfered 3 months, without an identifiable cause. | other forms of urticaria, such as physical, drug-induced, acute, or cholinergic urticari and any systemic disease or dermatologic disease that with the evaluation of the symptoms | Mean age 42 yrs 41% male Ethnicity NR | Levocetirizine, 5 mg, vs. placebo | No relief or rescue medication was provided; an analysis of the concomitant medications linked to urticaria reported was performed | Patients used daily record cards to record their symptoms once a day in the evening. A four-point scale from absent (0) to severe (3) was used to evaluate pruritus severity over the last 24 h. The number of wheals was reported using a 0–3 scale (0, no wheals; 1, 1–6 wheals; 2, 7–12 wheals; 3, 12 wheals) and their size was evaluated using a similar scale. The duration of pruritus was evaluated daily by the patients using a four-point scale (0, no pruritus; 1, < 1 h; 2, 1–6 h; 3, 6 h). At each visit, the investigator evaluated the same parameters using the same scales, and also indicated the presence or absence of dermographism (urticaria factitia), angioedema, and pressureinduced urticaria. End-of-treatment visit, a global evaluation scale (7 points) was completed by answering the question: “Overall, has there been a change in your urticaria since the start of the study medication?” | 42 (33 placebo (38.8%) and 9 levocetirizine 5 mg group (11.1%)/0/166 | Levocetirizine vs.placebo at 4 weeks Pruritus severity score (SE) 1.56 (0.09) vs. 0.94 (0.09) P< 0.001 Duration of pruritus (SE) 1.57 (0.09) vs. 0.98 (0.09) P < 0.001 Number of wheals (SE)1.51 (0.10) vs. 1.04 (0.10) P = 0.001 Size of wheals (SE) 1.35 (0.09) vs. 0.96 (0.09) P = 0.001 Change in DLQI 7.3 vs. 2.4 absenteeism 0.8 working days lost per month vs.1.8 working days lost per month overall loss of productivity −0.5 days vs, + 1.5 days per month |
| Monroe 2003 North America, South America, Europe | RCT, DB, parallel-group, multicenter | CIU Patients aged 12 years or older, of either sex and any racial group, with documented signs and symptoms of CIU for 6 weeks or more; CIU flare for 3 weeks or more before screening, with urticarial lesions visible 3 days or more per week. Overall severity had to be at least moderate at screening and baseline, patients had to have at least moderate pruritis, and hives had to be apparent at screening; total reflective pruritus score of 14 or greater over the last 3 days of the screening period and the morning of the baseline visit. Routine laboratory test results and ECG parameters obtained during screening had to be within clinically acceptable limits. Women of childbearing age had to have a negative serum pregnancy test result at screening and use an acceptable method of birth control throughout the trial. | Concomitant illness or required pharmacologic treatment that could interfere with the status of their CIU; previous nonresponse to antihistamines, 2 or more drug allergies, previous intolerance of desloratadine or other antihistamines, need for long-term inhaled or oral corticosteroids in patients with asthma, investigational drug therapy within 30 days, chronic urticaria due to physical factors or food allergy, and pregnancy or breast feeding. Patients who were unable to keep an accurate diary of disease symptoms were also excluded from the study. | 40.5 years (range 13–84) 24.7% male 70.8% white, 4.0% black, 6.6% Asian, 16.4% Hispanic, 2.2% other | D: desloratadine 5 mg P: placebo | NR | Efficacy and safety assessments at day 4 and weeks 1, 2, 4, 6. Patients provided with diary cards at screening, baseline, and weeks 1, 2, and 6. Diary cards were completed twice daily and were collected and reviewed at baseline and visits 3–7. CIU signs and symptoms (pruritus, number of hives, size of largest hive in cm, interference with sleep, and interference with daily activities) evaluated using 4-point scales. Severity of CIU assessed jointly by the investigator and patient/guardian at all study visits (4-point scale; 0=none, 1=mild, 2=moderate, 3=severe). Therapeutic response to study medication also assessed jointly by investigator and subject/guardian at visits 3–7 (1=complete relief, 2=marked relief, 3=moderate relief, 4=slight relief, and 5=treatment failure). | 51/3/226 | Mean improvement from baseline in patient-evaluated mean AM/PM reflective pruritus score over first 7 days of treatment: D: 1.05 (47.9%) P: 0.52 (21.9%) p<0.001 Improvement in instantaneous TSS over first 7 days: D: 42.8% P: 24.3% p=0.004 Improvement in AM/PM reflective TSS over days 1–8: D: 43.3% P: 21.4% p<0.001 Improvement in interference of CIU with sleep at days 1–8: D: 44.0% P: 14.4% p=0.007 Improvement in interference of CIU with daily activities at days 1–8: D: 46.9% P: 17.2% p=0.001 Improvements on the above outcomes were seen by the first evaluation (day 2; 24 hours after first dose) Joint patient/investigator assessment of overall condition of CIU found D significantly better than P at all time points (p<0.001, data NR) |
| Nettis 2006 Italy | DB RCT Single center | Patients with delayed pressure urticaria (DPU) | Concomitant illness (e.g. malignancies or hepatic, psychiatric, endocrine or other major systemic diseases), pregnancy, pregnancy potential or currently breastfeeding. | Mean age 35 58% male Ethnicity NR | Oral desloratadine 5 mg plus oral placebo vs. oral desloratadine 5 mg plus montelukast 10 mg vs. oral placebo alone. | Medications that could interfere with the clinical evaluations and systemic or topical medication for urticaria, other than those specified in the study treatment, were not allowed during the trial | The difference in weal size (pressure challenge lesion area) between baseline and the end of the 2-week treatment, self-evaluation of skin lesion scores regarding erythema, oedema and pruritus, using a four-point scale (0, none - 3,severe), and by the decrease of number of separate urticarial episodes (0, no episodes - 3, more than three episodes). | 2/0/34 | desloratadine plus montelukast vs. desloratadine Mean score decrease TSS value 97.2% vs. 41.1% Pruritus score 70.8% vs. 53.9% Erythema score 66.7% vs. 34.8% Oedema score 73.9% vs. 36.4% Number of episodes score 61.1% vs. 42.2% desloratadine plus montelukast vs. desloratadine vs. placebo (baseline/endpoint) mean (SD) Pressure challenge diameter (mm) 13.7 (1.6)/0.8 (1.9) vs. 13.4(1.5)/7.0(4.7) vs. 12.8(1.9)/11.8 (2.2) Pruritus score 2.4(0.8)/0.7(0.5) vs. 2.6(0.7)/1.2(0.6) vs. 2.3(0.9)/2.5(0.8) Erythema score 2.4(0.7)/0.8 (0.8) vs. 2.3(0.6)/1.5 (0.7) vs. 2.4(0.8)/2.4(0.8) Oedema score 2.3(0.8)/0.6(0.8) vs. 2.2(0.9)/1.4(0.8) vs. 2.4 (0.8)/2.4(0.7) Number of separate episodes score 1.8(0.8)/0.7(0.5) vs. 1.9(0.8)/1.1(0.5) vs. 1.7(0.9)/1.5(0.7) |
| Nettis 2006 Italy | DB RCT Single center | Diagnosis of chronic idiopathic urticaria | Physical urticaria, or urticaria caused by medications, insect bites, food or other known causes, as well as a history of atopic diseases. Patients with significant concomitant illness (e.g. malignancies or hepatic, psychiatric, endocrine or other major systemic diseases) | 39 years old 37% male Ethnicity NR | Oral levocetirizine 5 mg, vs. oral placebo 6 weeks | “No medications that could interfere with the clinical evaluations were allowed during the trial.” | Patients recorded their symptoms in a daily diary, including pruritus, size of weals, number of weals, number of separate urticarial episodes. | 6/0/100 | Levocetirizine 5 vs. placebo Mean TSS value decrease 81% vs. 1% Total disappearance of symptoms 27 (53%) vs. 0 The rest of the outcomes only report active results and not placebo |
| Ortonne 2007 France | DB RCT Multicenter (40) | Moderate to severe chronic idiopathic urticaria patients; active for 3 weeks or longer; with wheals for at least 3 days a week and a global CIU severity score of 2 or more; greater than 18 years old. | Hospitalized for CIU aggravation in the 3 months or if they had urticaria due to physical or other known causes, skin or food allergies that manifested as skin reactions, prior to antihistamine treatment, a history of hypersensitivity to desloratadine or any of its excipients, or asthma requiring long-term treatment with inhaled or systemic corticosteroids; investigational medications in 30 days prior or investigational antibodies for asthma or allergic rhinitis in the 90 days; individuals with clinically significant psychiatric, cardiovascular, or other pathologic conditions that could interfere with the study evaluation, compromise patient safety, or patient’s consent to partake; history of poor motivation or non-compliance with medications or treatment protocols. | Mean 41 years 39% male Ethnicity NR | desloratadine 5mg daily vs. placebo 6 weeks | NR except the excluded drugs | pruritus severity, number of wheals, and the size of the largest wheal assessed 2x a day and overall therapeutic response at the end of the 6-weeks | 52/3/137 | Desloratadine vs placebo Complete, marked, or moderate therapeutic response 68.8% vs. 36.8% P < 0.001 Reduction of pruritus scores (SD) −1.43(0.93) vs. −0.86(1.14) P = 0.004 |
| Potter 2009 Multinatiional | DB RCT Multicenter | Male and female out-patients aged 18 years and over, with a clinical history of CIU (i.e. episodes of hives of characteristic wheal and flare appearance, occurring regularly, at least three times a week) for a period of at least 6 weeks during the last 3 months without an identifiable cause | Physical urticaria, drug-induced urticaria, urticarial vasculitis, senile pruritus or hereditary angioedema, any dermatological or any other clinically significant disease, received systemic and topical corticosteroids within 4 weeks, desloratadine, loratadine, levocetirizine or cetirizine,within 10 days, astemizole within 12 weeks, ketotifen within 2 weeks, and leukotriene antagonists within 3 days, received CNS acting agents (including tranquilizers, antidepressants, sedatives, hypnotics or antiepileptics) at any time and pregnant or breastfeeding. | 43.1 years 33.4% male 81.6 % Caucasian 13.7% Asian/Pacific Islander 1.5% Black 3.3% other | Levocetirizine 5 mg vs.desloratadine 5 mg | Yes- concomitant medication use was recorded | Mean pruritus severity score after 1 week of treatment and mean pruritus severity score over 4 weeks and pruritus duration score, number and size of wheals, mean CIU composite score (sum of the scores for pruritus severity and numbers of wheals), quality of life, and the patient s and investigator s global satisfaction with treatment, | 54/6/886 | Levocetirizine vs.desloratadine Pruritus severity score First treatment week 1.02 (0.04) vs. 1.18 (0.04) P < 0.001 Entire treatment period 0.86 (0.04) 434 0.99 (0.04) P = 0.004 Pruritus duration score First treatment week 1.08 (0.04) vs.1.24 (0.04) P = 0.002 Entire treatment period 0.93 (0.04) vs. 1.05 (0.04) P = 0.009 Number of wheals score First treatment week 0.96 (0.04) 434 1.05 (0.04) P = 0.054 Entire treatment period 0.85 (0.04) vs. 0.89 (0.04) P = 0.353 Size of wheals score First treatment week 1.01 (0.04) 434 1.12 (0.04) P = 0.025 Entire treatment period 0.89 (0.04) vs. 0.97 (0.04) P = 0.085 CIU composite score* First treatment week 1.98 (0.08) vs. 2.23 (0.08) P = 0.005 Entire treatment period 1.71 (0.07) vs. 1.88 (0.07) P = 0.041 |
| Active-control trials | |||||||||
| Breneman 1996 USA | RCT, DB, DD, placebo-controlled, parallel-group, multi-center | CIU Pts at lease 12 years of age with a documented history of chronic idiopathic urticaria that had occurred episodically for at least 6 weeks were studied. To qualify, pts were required to be symptomatic immediately before study entry. | Pts who were using concomitant antihistamines within 36 h prior to the start of the study; tranquilizers, hypnotics, antiepileptics, antidepressants, and agents that act on central nervous system within 1 wk of the start of the study; or astemizole within 6 wks of the start of the study were excluded; as were pts with asthma who required therapy using other means than an inhaled bronchodilator. | Age range: 34.5–38.8 69% female | C: cetirizine 10 mg qd H: hydroxizine 25 mg tid P: placebo | NR | Pts recorded the symptoms of urticaria experienced: total number of lesions 0 (none) to 3 (greater than 20); number of separate episodes more than one hour apart 0 (none) to 3 (greater than 3); average size of lesions 0 (none) to 3 (greater than 2.5 cm); average duration of lesions 0 (none) to 3 (greater than 12 h); and pruritus 0 (none) to 3 (severe, constant) in daily diary cards. Investigators and pts assessed efficacy by evaluation of symptoms and by global evaluations. | 7/NR/188 | TSS: C + H significant vs. P, p<0.006. *estimated from figure C vs H vs P: −8.5 (−64%) vs −8.7 (−68%) vs −5.3 (−42%) All other significant weeks 1–4 active treatment vs. P for lesion episodes (p=0.001), number/size/itching (p<0.05), or duration (p=0.001). Onset: C significantly better at day 1 than H in mean number of episodes greater than 1 hour apart (p<0.002). Responders: Definite or complete improvement significant active treatment vs. P (p<0.001). |
From: Evidence Tables
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