Methods

Randomised: method of randomisation not mentioned
Allocation concealment not mentioned
Double‐blind: yes
Intention‐to‐treat not mentioned
Follow‐up described
151 recruited; 89 (59%) completed study; 41% drop‐out
Design: parallel

Participants

N = 89; 42 male, 47 female
Age 1 to 15 years
Inclusion criteria: 2 of 3 major criteria ‐ purulent nasal discharge, cough, purulent pharyngeal drainage or 1 major and 2 minor criteria: facial pain, periorbital oedema, earache, tooth pain, sore throat, headache, increased wheeze, fever, foul breath for more than 7 days and Rx criteria
Water radiographs at the beginning of study positive if complete opacification or maxillary mucoperiosteal thickening more than 4 mm. 79 participants had positive Rx
Exclusion criteria: history of allergic rhinitis, asthma, recurrent/chronic sinusitis
Baseline characteristics: similar in both groups, no significant differences
Patients maintained daily symptom cards and were examined by the same physician each week. Symptom scores were evaluated by a scale from 0 to 3

Interventions

Tx group: budesonide 50 µg bid nasal spray to each nostril, N = 43
C group: placebo nasal spray bid, N = 46
All participants in both groups received amoxicillin‐clavulanate potassium 40 mg/kg/day tid
Duration: 3 weeks

Outcomes

Difference in weekly symptom scores for cough and nasal discharge in the first, second and third week of the study in both groups, as difference between groups or change from baseline
Relapse: results were reported as medians of scores using non‐parametric tests because a wide range of scores without normal distribution

Notes

Marmara University Hospital Outpatient Clinic patients enrolled from November 1993 to October 1994
Informed consent signed by all parents. 151 patients enrolled, 89 completed study, 62 dropped out, no separate data for both groups
Reasons for drop‐outs: non‐compliance with weekly visits or not recording daily symptoms

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomised, method not mentioned

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No separate data for groups, ITT not mentioned

Selective reporting (reporting bias)

Low risk

No evidence of reporting bias

Other bias

Unclear risk

‐

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blind

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

‐

Methods

Multicentre randomisation ‐ permuted blocks scheme stratified by site with a block size of 4 generated using SAS version 6.12
Allocation concealment ‐ study kits administered sequentially by blinding site personnel to block size
Blinding: yes
Intention‐to‐treat: yes
Follow‐up described: yes
88 (93%) completed study
Design: parallel

Participants

N = 95; 30 men, 65 women
Age 30 to 50; median age 39 years
Inclusion criteria: older than 18 years, history of recurrent sinusitis or chronic rhinitis and clinical evidence of acute sinusitis confirmed Rx or by nasal endoscopy
Diagnosis of acute sinusitis: clinical criteria ‐ participants with 2 of the 5 following symptoms present were enrolled: headache, facial pain, nasal congestion, thick coloured nasal discharge, olfactory disturbance
Rx criteria: air‐fluid level, mucosal thickening or opacification of sinus
Exclusion criteria: previous sinus surgery, sinus lavage in the past 7 days, nasal polyposis, recurrent epistaxis, chronic bacterial sinusitis with failure of antibiotic therapy, INCS use within past 14 days, chronic use of corticosteroids or immunosuppressives, immunocompromised, allergy to penicillin/cephalosporins, participants without a telephone, pregnant, nursing women
Baseline characteristics ‐ similar in both groups, no significant differences
Participants assessed at baseline, 10, 21, 56 days by diary records and telephone follow‐up

Interventions

Tx group: nasal spray fluticasone propionate 2 puffs (total dose 200 µg) once daily in each nostril; N = 47
C group: nasal spray placebo 2 puffs once daily in each nostril; N = 48
All participants in both groups received 2 puffs xylometazoline hydrochloride in each nostril twice daily 10 minutes before the study nasal spray and 250 mg cefuroxime axetil twice daily for 10 days
Duration of study: 21 days
Follow‐up: 8 weeks
Allowed to continue: NSAIDs, analgesics, immunotherapy for allergies, orally inhaled corticosteroids
Not permitted during study: oral decongestants, mucolytics, corticosteroids oral or parenteral, antihistamines, immunosuppressives
Sinus lavage or sinus surgery was discouraged during the first 3 weeks of the trial, antibiotic use in the past 7 days or 21 days if longer half‐life was not permitted
Compliance with Tx: assessed by a standardised form given to patients for recording daily symptoms, Tx, adverse events, work attendance. 94% completed study Tx without difference between groups

Outcomes

Proportion of patients with clinical success (cured or much improved) at 10, 21, 56 days on telephone follow‐up
Time to clinical success differences over time in sinusitis and quality of life scores
Level of work performance
Total number of hours lost from work
Recurrences

Notes

Study conducted between October 1998 to April 2000 at 22 sites (12 primary care and 10 otolaryngology)
Equal proportions of participants from primary care and otolaryngology practices in both treatment arms
All study sites received standardised instructions for conducting the study
Study progress monitored by a research associate
Patients assessed symptoms on numeric scales and received booklets with specific instructions for use of nasal spray
High agreement between patient‐recorded and interviewer‐obtained symptoms
Drop‐outs:
Tx group: 1 ‐ rash, 1 ‐ unknown, 1 ‐ lost to follow‐up
44 completed 21‐day Tx and telephone follow‐up, 36 completed diary, 46 included in primary analysis
C group: 1 ‐ withdrew, 2 ‐ switched to different antibiotics
45 completed 21‐day Tx, 44 completed telephone follow‐up, 32 completed diary, 46 included in primary analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

See methods

Allocation concealment (selection bias)

Low risk

See methods

Incomplete outcome data (attrition bias)
All outcomes

Low risk

See methods

Selective reporting (reporting bias)

Low risk

No evidence of selective reporting

Other bias

Low risk

‐

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

See methods

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

‐

Methods

Multicentre randomisation
1:1:1:1 ratio to 1 of 4 arms by computer‐generated code
Allocation concealment: not mentioned
Double‐blind: yes
Intention‐to‐treat: yes
Follow‐up described
10% drop‐out in Tx phase, 95% completed follow‐up phase
Design: parallel

Participants

N = 981; 338 men, 643 women
Age 12 to 76 years
Inclusion criteria: age more than 12 years with clinical criteria for acute sinusitis; MSS more than 5 but less than 12 at baseline, assessed by participant and investigator and no more than 3/5 symptoms rated severe (rhinorrhoea, PND nasal congestion, stuffiness, sinus headache and facial pain on pressure) adding cough to the TSS
Exclusion criteria: fulminant bacterial rhinosinusitis, chronic rhinosinusitis, nasal/sinus surgery within the last 6 months for this condition, otitis, atrophic rhinitis, nasal polyps, symptomatic seasonal allergic rhinitis, allergy to corticosteroids
Asthmatic participants needed to be stable last 30 days and FEV1 more than 65% last 3 months before screening
Rhinoscopic examination was performed at all visits
Participants were assessed at baseline days 8, 15, 29 and monitored by telephone on days 3 to 4. Response to Tx evaluated by participant and investigator as scores for symptoms on a scale from 0 to 3
Baseline characteristics similar for all the arms

Interventions

4 groups
Tx groups:
1. MFNS 200 µg once daily nasal spray + placebo nasal spray once daily + placebo capsules tid; N = 243
2. MFNS 200 µg nasal spray bid + placebo capsules tid; N = 235
3. amoxicillin 500 mg tid for 10 days + placebo nasal spray bid; N = 251
C group: placebo nasal spray bid + placebo capsules tid; N = 252
Duration of study: 15 days
Capsules given for 10 days
Follow‐up: 14 days
Not allowed during study: nasal saline, nasal cromolyn sodium, ipratropium bromide, corticosteroids (excluding oral inhaled corticosteroids for mild/moderate asthma), antihistamines, decongestants, leukotriene pathway modificants, analgesics, NSAID
Compliance assessed at days 8 and 15 by questioning whether drug had been taken
Each participant received at least 1 dose of study drug

Outcomes

Mean MSS
Mean TSS
Individual scores
Time to onset of action
Global response to Tx
Adverse events
Disease recurrence
Tx failure (worsening or not improvement in symptoms during the Tx phase)

Notes

Study conducted at 71 medical centres in 14 countries from January to September 2003
Drop‐outs: during the Tx phase in the 200 µg, 400 µg MFNS, amoxicillin, placebo were 9%, 9%, 8%, 13%
Reasons for discontinuation: adverse events, Tx failure, loss to follow‐up, did not wish to continue, non‐compliance with protocol, did not meet protocol criteria for entry

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

See methods

Allocation concealment (selection bias)

Unclear risk

See methods

Incomplete outcome data (attrition bias)
All outcomes

Low risk

See methods

Selective reporting (reporting bias)

Low risk

‐

Other bias

Unclear risk

‐

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

See methods

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

‐

Methods

Multicentre, randomised; method of randomisation not mentioned
Allocation concealment not mentioned
Double‐blind: yes
Follow‐up described: yes
864 (89%) participants included in the primary efficacy analysis
Design: parallel

Participants

N = 967; 402 men, 565 women
Age 8 to 78 years
Inclusion criteria: acute episode of rhinosinusitis, at least 1 moderate/severe nasal symptom (these may include purulent rhinorrhoea, stuffiness/congestion, post‐nasal drip, sinus headache, facial pain, cough), purulent rhinorrhoea present, sinusitis confirmed by a CT scan, which is read by a radiologist at each study site at baseline, a total symptom score more than 6
Exclusion criteria: nasal polyps, cystic fibrosis, Kartagener syndrome, expected immediate sinus or nasal surgery, glaucoma, history of subcapsular cataracts, clinical significant diseases
Symptoms evaluated at baseline (day 1) and day 21 by patient and investigator by scales. Patients evaluated at baseline, 15, 21 days
CT scans of paranasal sinuses at baseline and 21 days evaluated by an independent blinded radiologist
Similar baseline characteristics and baseline symptoms scores in all 3 groups
Patients recorded symptom scores, adverse events and use of medication twice daily

Interventions

3 groups
Tx groups:
1 MFNS 400 µg nasal spray twice daily; N = 324
2 MFNS 200 µg nasal spray twice daily; N = 318
C group:
Matching placebo nasal spray twice daily; N = 325
All participants in all groups received amoxicillin‐clavulanate potassium 875 mg twice daily for 21 days
Not allowed during study: any form of corticosteroid, nasal decongestants, antihistamines
Washout period before the baseline visit for previous use of antibiotics, intranasal or systemic corticosteroids, decongestants
Adherence to therapy assessed by weighing the nasal spray dosing containers without patients' knowledge

Outcomes

Improvement in total symptoms score
Improvement in individual symptom score
Overall response to treatment: proportion of participants with complete or marked relief
Onset of relief
Evaluation of changes in CT scans of sinuses
Adverse events

Notes

Outpatients from 61 Tx centres in the US
967 participants randomised, 103 participants (11%) not included in analysis because CT did not confirm sinusitis and excluded post‐randomisation, diary data not available, less than 80% compliance with Tx, less than 7 days Tx (32, 36, 35 in the MFNS 400, 200 µg and placebo groups)
Reasons for exclusion or discontinuation were evenly distributed among the groups
Physician evaluation of symptoms at day 21 was consistent with patient‐recorded evaluation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

See methods

Allocation concealment (selection bias)

Unclear risk

See methods

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

See notes

Selective reporting (reporting bias)

Unclear risk

‐

Other bias

Unclear risk

‐

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

See methods

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

‐