| Author Year Country (Quality rating) | 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| Method of outcome assessment and timing of assessment | Number screened/eligible/enrolled | Number withdrawn/lost to fu/analyzed | Efficacy results | Safety results | Adverse events: behavioral, cognitive, psychomotor development |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ETAC (Early Treatment of the Atopic Child) Trial Diepgen et al. 2002 (efficacy); Simons et al., 1999 (safety); Stevenson et al., 2002 (adverse events: behavioral, cognitive, psychomotor development) Multiple European countries and Canada (Fair) | Double-blind, placebo- controlled, parallel group, multicenter | Infants 1 to 2 years, with active symptoms of atopic dermatitis for at least 1 month before inclusion and at least one parent or sibling with a history of atopic dermatitis, allergic rhinitis, or asthma. | Infants with asthma, or with a history (beyond the age of 6 months) of one or more episodes of wheezing or nocturnal cough as well as any conditions that might obscure the diagnosis of asthma. Weight below the third percentile, chronic pulmonary disease, severe neurologic or psychologic disorder, any third disease likely to interfere with the study drug, clinically relevant cardiac disease, any anomaly of the QT interval on ECG tracing, a history of sleep apnea in the subject or siblings, neonatal distress, prior desensitization or immunotherapy, prior treatment with medicines interfering with the immune system, hypersensitivity to cetirizine or other piperazines or parabens, and participation in a clinical study within 3 months before randomization. | 17.0 months (SD4.1) 62.1% male Race/ethnicity NR | A: cetirizine oral solution 0.50 mg (0.25 mg twice daily) B: placebo twice daily 18 months | All concomitant medications were allowed but had to be recorded by the parents/guardians on the diary card and by the investigator in the case report form. Investigators were discouraged from using antihistamines except when considered absolutely necessary | (Primary outcome was reduction in incidence of asthma.) Secondary efficacy outcomes included any reduction in severity of symptoms related to atopic dermatitis. Severity of atopic dermatitis rated with SCORAD rating scale. Assessments at baseline, 1 month, 3 months, and thereafter every 13 weeks during the 18-month treatment period. Between visits, parents/guardians were contacted additionally be telephone. At each visit, infants underwent a physical exam where the status of atopy, the severity of AD according to SCORAD, the consumption of concomitant topical and systemic medications, and the occurrence of any concurrent illness were recorded. | 830/NR/NR | 99/NR/795 | Severity of atopic dermatitis decreased in both groups over 18 months; but NSD between cetirizine and placebo. Change from baseline to 18 months in SCORAD Cetirizine: −9.7 Placebo: −9.4 (NSD) Concomitant use of oral H1-antihistamines: Cetirizine: 18.6% Placebo: 24.9% (p=0.03) In subset of patients with more severe SCORAD at baseline (≥ 25 points; 43.7% of patients): Severity decreased significantly in both groups, but no treatment effects. Concomitant use of corticosteroids: Cetirizine: 25.8% of days (median 6.2) Placebo: 35.1% of days (median 20.2) (p=0.014) | Serious adverse events (cetirizine vs placebo) 37/399 children (9.3%) vs 54/396 children (13.6%) p=0.053 Serious adverse events attributed to study medicaiton 1 child vs 5 children Neurological symptoms or events (cetirizine vs placebo) Ataxia (loss of balance): 2 vs 2 (p=1.00) Febrile convulsions: 2 vs 4 (p=0.45) Fatigue: 13 vs 15 (p=0.093) Emotional lability: 5 vs 6 (p=0.772) Hyperkinesia: 5 vs 9 (p=0.296) Insomnia: 35 vs 21 (p=0.071) Nervousness: 5 vs 7 (p=0.577) Other: 5 vs 6 (p=0.772) Somnolence: 9 vs 8 (p=1.00) Total: 65 vs 55 (p=0.373) Hospitalizations: 36 cetirizine, 47 placebo (p=0.189) Most common reasons for hospitalization were infection-related events without asthma (12 cetirizine vs 18 placebo) or injury, surgery, or procedure (8 cetirizine vs 15 placebo) 2 cetirizine and 8 placebo had accidental overdose. Height and weight: Children in both groups had age-appropriate gains in height and weight over 18 months. Cetirizine-treated children weighed significantly less than placebo-treated children at baseline. At other time points, differences were not significant. Mean weight after 18 months: cetirizine: 14.82 kg (SD 1.89) placebo: 14.57 kg (SD 1.87) ECG (missing baseline data on 13 cetirizine-treated and 9 placebo-treated children; missing followup data on 49 cetirizine-treated and 54 placebo-treated children): All within normal limits at baseline and 2 followup visits; no difference between groups in mean corrected QT interval; no child receiving cetirizine had an increase in QT interval. | Behavior problems (measured by BSQ behavioral screening questionnaire): No effect of cetirizine on children’s behavior or a rebound effect after terminating the treatment period. Overall estimated treatment effect as (difference in overall means for cetirizine and placebo): 0.12 (95% CI −0.34, 0.58). Cognitive ability (measured by GCI, a composite scale of the MSCA, measuring verbal, perceptual performance, quantitative memory, and motor aspects, scaled according to age, normal range is 84–116): Overall estimated treatment effect (overall difference in cetirizine and placebo means): −0.81 (95% CI −4.06, 2.43). Developmental milestones (gross motor, fine motor, and speech/language development): No significant differences between groups. |
| Simons 2007 Early Prevention of Asthma in Atopic Children (EPAAC) 10 European countries, Australia, and South Africa. | Randomized, double- masked, parallel-group, placebo-controlled, multi- center | Age 12–24 months, had atopic dermatitis, elevated specific IgE to either grass pollen or house dust mite, and a family history of allergy. | Asthma or any other systemic disease; height or body mass were below the 5th percentile; any severe neurologic or psychologic disorder requiring medical treatment; intolerant of levocetirizine or any other piperazine antihistamine, or to the parabens used as preservatives in H1-antihistamine liquid formulations; a personal history or sibling history of sleep apnea; or renal insufficiency or any metabolic condition that might affect the elimination of levocetirizine. | Mean age 19.35 months 62.6% male | Levocetirizine 0.125 mg/kg or placebo twice daily for 18 months. | NR | Adverse events captured by spontaneous reporting on the diary cards, and by asking the child’s caregiver, at each scheduled visit, “Did you notice anything unusual about the child’s health since the last visit?” Preventing or delaying asthma and the efficacy of levocetirizine in preventing urticaria - to be published in another publication | NR/NR/510 | 75/NR/510 | NR | Levocetirizine vs. Placebo One or more adverse events 247 (96.9%) vs. 244 (95.7%) Treatment-attributed adverse events 13 (5.1%) vs. 16 (6.3%) Serious adverse events 31 (12.2%) vs. 37 (14.5%) Treatment-attributed serious adverse events 0 vs. 1 (0.4%)* Adverse events that led to discontinuation (treatment–emergent) 5 (2.0%) vs. 3 (1.2%) Wheezing 12 (4.7%) vs. 19 (7.5%) Dermatitis, atopic 3 (1.2%) vs. 6 (2.4%) Gastroenteritis 2 (0.8%) vs. 5 (2.0%) Cough 4 (1.6%) vs. 2 (0.8%) Bronchopneumonia 4 (1.6%) vs. 1 (0.4%) Febrile convulsion 4 (1.6%) vs. 0 Urticaria 1 (0.4%) vs. 3 (1.2%) Bronchitis, chronic 0 vs. 3 (1.2%) Pneumonia 2 (0.8%) vs. 0 Abnormal behavior 2 (0.8%) vs. 3 (1.2%) Aggression 0 vs. 1 (0.4%) Agitation 1 (0.4%) vs. 0 Anxiety 0 vs. 1 (0.4%) Burning sensation 0 vs. 1 (0.4%) Convulsions 1 (0.4%) vs. 0 Epilepsy 1 (0.4%) vs. 0 Febrile convulsions 5 (2.0%) vs. 1 (0.4%) Headache 1 (0.4%) vs. 4 (1.6%) Insomnia 3 (1.2%) vs. 2 (0.8%) Irritability 0 vs. 4 (1.6%) Nervousness 1 (0.4%) vs. 0 Nightmare 0 vs. 1 (0.4%) Sleep disorder 1 (0.4%) vs. 1 (0.4%) Somnolence 0 vs. 1 (0.4%) Syncope 0 vs. 1 (0.4%) | Levocetirizine vs. Placebo Median (range) Gross motor development Sit alone 6 (6–7) vs. 6 (6–8) Crawl 8 (7–10) vs. 8 (7–10) Stand alone 10 (9–12) vs. 10 (9–12) Walk alone 12 (11–14) vs. 12 (11–14) Climb stairs with assistance 14 (12–16) vs. 14 (13–17) Climb stairs without assistance 17 (14–20) vs. 18 (15–20) Run 16 (14–18) vs. 16 (14–19) Fine motor development Pincer (2-finger) grip 10 (8–13) vs. 11 (7–14) Pencil (3-finger) grip 17 (12–21) vs. 18 (12–21) Match cubes (build 4 block tower) 18 (14–20) vs. 18 (14–20) Show hand preference 17 (12–23) vs. 18 (12–22) Speech and language Pronounce first five words 14 (12–18) vs. 15 (12–18) Name many objects 18 (15–22) vs. 18 (16–22) Pronounce short sentences 22 (19–25) vs. 23 (20–25) |
From: Evidence Tables
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