Garavaglia 1995.

Methods	Design: randomised double‐blind 6‐week study of cetirizine vs terfenadine vs placebo in CSU; parallel 3‐arm trial Duration: 6 weeks
Participants	Number of participants randomly assigned: n = 63 took part in the study; however as participants dropped out, they were replaced, so 47 are presented (number given cetirizine n = 17; terfenadine n = 16; placebo n = 14) Sex: cetirizine: 29.41% male, 70.59% female; terfenadine: 18.75% male, 69.23% female; placebo: 69.23% male, 30.77% female Age of participants, years: cetirizine 33.8 ± 13.8; terfenadine 35.88 ± 17.3; placebo 37.8 ± 16.45 Unit of allocation: participant Country and setting: Argentina; outpatient research clinic Inclusion criteria of the trial Participant's written consent to study conditions. 6‐week history of regular attacks of idiopathic urticaria: minimum frequency of 3 episodes per week Exclusion criteria of the trial Younger than 18 years of age, pregnant women or women with potential for pregnancy, serious renal or hepatic dysfunction, dependent on corticosteroids, taking drugs that interfere with cutaneous reactions unless they had stopped these before entry into the study; urticaria of known causes (contact, pressure, cold, heat, cholinergic, dermographism) Previous unresponsiveness to antihistamine: not stated
Interventions	Interventions, dose, duration Placebo, cetirizine 10 mg per day, 1 tablet Terfenadine 120 mg per day, 2 tablets Duration of intervention: intermediate‐term (6 weeks) Length of follow‐up: 6 weeks
Outcomes	Timing of outcome assessment: 3 visits in total, initial at 3 weeks and final at 6 weeks from start of study Primary outcomes of the trial Routine physical examination, including heart rate, blood pressure, height, weight Clinician assessed the following: giant papules present or absent, papules present or absent; if papules present, fewer, or more than 20, erythema present or absent, oedema present or absent; objective description of lesions including distribution, size, location. Participant report: visits 1 and 2: Participants were asked to complete daily diary cards to record their assessments of intensity of itching, redness and papules. Symptom report of mild, moderate or intense based on a visual analogue scale Quality of life measures: none Secondary outcomes of the trial Overall efficacy and tolerance assessed at end of study by participant and clinician Adverse events: types of adverse events reported. Total adverse events: 2/17 in cetirizine, 2/16 in terfenadine. Types of adverse events reported: cetirizine: gastritis, dyspepsia, dry mouth, bitter taste, somnolence; terfenadine: morning sickness, menstrual alteration (delay, pain), shortening of cycle. No participant abandoned the study because of intolerable adverse effects Participants were withdrawn if they had adverse reactions, interruption of medication for up to 3 days on more than one occasion, concomitant use of other active medication, withdrew consent, did not co‐operate, violated study protocol, did not attend follow‐up sessions, or there were other reasons (not specified) at the researcher's discretion. Clinician or participant report: clinician and participant
Notes	Study report written in Spanish Study investigators concluded that cetirizine is superior to terfenadine in terms of efficacy and tolerability; for symptom control, both active drugs were significantly better than placebo
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote (page 180): "Randomly divided (in threes) into three equal groups" However, if participants dropped out, they were replaced with new participants (14 did not take the medication, 35 did not return for assessment, 37 did not take the correct medication. All of these participants were replaced). As participants who dropped out were replaced with new participants, it is unclear whether the trial design is truly randomised; it is not clear whether new participants were randomly assigned de novo or were assigned to the group of the most recent dropout. The trial report states: "since the randomisation was performed on groups of 3, it was actually necessary for each loss of a patient [to result in resumed] treatment of three patients" (page 182) (page 186) "9 patients were replaced as three were withdrawn due to protocol violations (lost medication, did not attend tests, did not take correct medication). Therefore 9 new [participants] were recruited, as randomisation was [done] in threes"
Allocation concealment (selection bias)	Unclear risk	Not stated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Tablets and dosages prepared to be identical (boxes of white round tablets), presented so that each drug or placebo was administered in a uniform way. A scratch‐off label would reveal the drug type in case of emergency
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Outcome assessors (clinicians and participants) would not have had indications of treatment group because of uniform packaging, but methods of blinding are not explicitly stated
Incomplete outcome data (attrition bias) All outcomes	High risk	47/63 completed. Dropped out: 3/17 in cetirizine; 3/16 in terfenadine; 9/14 placebo. 15 left the study because of inefficacy and were not replaced; they were "statistically computable" (page 186). It is unclear how results were computed for participants who dropped out because of inefficacy. Note: This may have introduced bias, as the study was possibly biased towards positive results Other reasons for dropout: adverse events: 2/17 in cetirizine; 2/16 in terfenadine due to adverse events No participant left the study because of intolerable adverse reactions
Selective reporting (reporting bias)	High risk	Only results for the cetirizine and terfenadine arms of the study were included in the published report. No results were presented for the placebo arm The researcher was able to withdraw participants on the basis of his opinion
Other bias	Unclear risk	Funder: not stated Analyses were not statistically significantly different and placebo results were not presented; therefore conclusions of the study as stated in the study report are unreliable