Small 2005.
| Methods | 3‐arm, double‐blind, multicentre, parallel‐group RCT, with 4‐month duration of treatment and follow‐up | |
| Participants |
Location: 44 medical centres "worldwide" Setting: no information Sample size: Number randomised: 122 in 400 µg, 115 in 200 µg, 117 in placebo group respectively Number completed: 109 in 400 µg, 101 in 200 µg, 95 in placebo group respectively Participant (baseline) characteristics:
Inclusion criteria: ≥ 18 years with an endoscopically confirmed diagnosis of bilateral nasal polyps (at least 1 on a scale of 0 to 3) and clinically significant nasal congestion/obstruction (average morning score 2 or higher on as scale of 0 to 3 for each of the last 7 days of the 14‐day run‐in period) If had asthma, had a documented FEV1 ≥ 80% of the predicted value within the 6 months before screening and no asthma exacerbations within 30 days before screening. Those treated with inhaled corticosteroids were required to be on a moderate, stable regimen of beclomethasone dipropionate ≤ 800 mg/d or equivalent for 1 month before screening and to remain on a stable regimen throughout the study period. Exclusion criteria: Seasonal allergic rhinitis within the past 2 years Sinus or nasal surgery within the previous 6 months or 3 nasal surgeries (or any surgical procedure preventing an accurate grading of polyps) Presumed fibrotic nasal polyposis, or complete or near complete nasal obstruction Nasal septal deviation requiring corrective surgery Nasal septal perforation Acute sinusitis, nasal infection or upper respiratory tract infection at screening or in the 2 weeks before screening; ongoing rhinitis medicamentosa Churg‐Strauss syndrome Dyskinetic ciliary syndromes Cystic fibrosis Glaucoma or a history of posterior subcapsular cataracts; allergies to corticosteroids or aspirin, or any other clinically significant disease that would interfere with the evaluation of therapy |
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| Interventions |
400 µg group (n = 122): mometasone furoate nasal spray 200 μg twice daily (morning and evening) for 4 months 200 µg group (n = 115): mometasone furoate nasal spray 200 μg once daily (morning, matching placebo used in the evening) for 4 months Placebo group (n = 117): placebo nasal spray twice daily (morning and evening) for 4 months Use of additional interventions (common to both treatment arms): Acetaminophen (paracetamol) was encouraged for analgesic purposes; NSAIDs limited to 5 consecutive days if alternative analgesia was required. Antibiotics were administered for bacterial infections at the discretion of the principal investigator. Concomitant medications that would interfere with study evaluations were not permitted, including nasal sodium cromolyn; nasal atropine or ipratropium bromide; corticosteroids (except oral inhaled corticosteroids for asthma or mild‐strength or mid‐strength topical corticosteroids for dermatologic purposes); antihistamines; decongestants; topical, oral or ocular anti‐inflammatory drugs; or topical nasal or oral antifungal agents. |
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| Outcomes |
Outcomes of interest in the review: Primary outcomes 1. Disease severity, patient evaluation of symptoms (congestion/obstruction, loss of sense of smell, anterior rhinorrhoea and postnasal drip) measured daily on a diary card on a 4‐point scale (0 = none, 3 = severe) 2. Significant adverse effect: epistaxis Secondary outcomes: 3. Other adverse effects: local irritation Other outcomes reported by the study: Polyps grade; bilateral score and proportion of patients demonstrating an improvement at endpoint Therapeutic response (rated by investigator) Peak nasal inspiratory flow Treatment compliance Number of withdrawals due to AE and events occurring in more than 2% of participants in any group |
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| Notes | Supported by a grant from the Schering‐Plough Research Institute | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "…randomised in a 1:1:1 ratio to 3 treatment arms…" Comment: no further information. However, this is a large multinational RCT and should have adequate resources to conduct proper sequence generation. |
| Allocation concealment (selection bias) | Low risk | Comment: no information provided. However, this is a multinational trial with adequate blinding and should have adequate sequence generation and allocation concealment procedures. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "double blind, double dummy"; "…matching placebo nasal spray …" Comment: pg 1276, col 1, para 1 and 2. "Matching placebo spray" mentioned and those on the 200 µg/day regimen were also given placebo nasal spray for the evening. |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: no information. Likely to remain well blinded until end of study. |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Quote: 305/354 patients (86%) patients "completed 4‐month treatment period" Comment: higher % of patients not completing in the placebo group 22/117 (19%); compared to the twice daily or once daily groups 13/122 (11%) and 14/114 (12%), respectively. Study mentioned analyses based on "all randomised subjects" using the "ITT principle" and endpoint was "defined as the last non‐missing reading for the subject" for bilateral polyps score; however, unlikely all were analysed as numbers do not tally exactly with the "meta‐analysis subsequently reported" |
| Selective reporting (reporting bias) | Low risk | Comment: all outcomes reported in the methods section were reported in the results section |
| Other bias | Unclear risk | Comment: no information about the validation of outcome measures |