Cassandro 2015.

Methods	4‐arm, non‐blinded, single‐centre, parallel‐group RCT, with 3 months of treatment and a total of 6 months follow‐up
Participants	Location: Italy, single site, between September 2011 and April 2012 Setting of recruitment and treatment: Department of Otorhinolaryngology of the University Hospital 'San Giovanni di Dio e Ruggi d'Aragona' in Salerno Sample size: Number randomised: 20 in intervention group, 20 in comparison group Number completed: no information Participant (baseline) characteristics: Age (mean ± SD): NS 38.6 ± 13.06, INCS: 38.4 ± 12.70 Gender (M/F): INCS: 10/10, NS:11/9 Main diagnosis: chronic rhinosinusitis with nasal polyps Polyps status: 100%, modified Lund‐Mackay score INCS about 23.1 (SD 1.3) in both groups Previous sinus surgery status: no information Previous courses of steroids: no information Other important effect modifiers, if applicable (e.g. aspirin sensitivity, comorbidities of asthma): Skin prick tests, % positive: INCS: 45, NS: 40 Smoking (%): INCS: 40, NS: 55 Time by the initial diagnosis (years) (mean ± SD): INCS: 4.45 ± 2.46, NS: 5.7 ± 5.19 Inclusion criteria: ≥ aged c18 years and had CRSwNP CRS defined as a duration of 12 weeks with the presence of at least 2 of the following nasal symptoms: inflammation of the nose and paranasal sinuses, nasal obstruction, postnasal drip, sneezing, cough, olfactory disturbance, facial pain, snoring, nasal dryness. Endoscopy and CT used in confirming diagnosis. Not received any investigational drug therapy for 4 months before study started Exclusion criteria: pregnant women
Interventions	Intranasal corticosteroid (n = 20): mometasone furoate nasal spray (MFNS) 200 µg twice a day Nasal saline (n = 20): nebulised saline administered as aerosol therapy (NEBULA®, Air Liquide Medical Systems Italy) with 5 ml of saline twice a day Use of additional interventions (common to both treatment arms): nasal decongestants and local anaesthesia were not used
Outcomes	Outcomes of interest in the review: Primary outcomes: 1. Disease severity symptom score using a validated 10 cm VAS for nasal obstruction, nasal discharge, postnasal drip, sneezing, cough, olfactory disturbance, facial pain, snoring and nasal dryness was recorded by the patient and guardian 2. Significant adverse effect: epistaxis Secondary outcomes: 3. Endoscopy, reported as "mean endoscopic score" ‐ scored by 2 otorhinolaryngologists using modified postoperative criteria for endoscopic appearance originally described by Lund et al 4. CT scan ‐ not fully reported 5. Adverse events: local irritation Other outcomes reported by the study: Active anterior rhinomanometry Saccharine clearance test
Funding sources	"Editorial assistance was provided by Raelene Simpson on behalf of in Science Communications, Springer Healthcare. This assistance was sponsored by IBSA". IBSA is the manufacturer of nebulised sodium hyaluronate, included in treatment arms not considered for this review
Declarations of interest	No information provided
Notes	There are 2 other intervention groups in this trial: Nebulised sodium hyaluronate (aerosol therapy with 3 ml sodium hyaluronate 9 mg and 2 ml saline twice a day) INCS plus nebulised sodium hyaluronate
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly assigned" Comment: no further description
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were randomly assigned" Comment: no further description
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote: "…drug was administered on an open‐label basis"
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "…drug was administered on an open‐label basis." Comment: subjective outcomes in a non‐blinded study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: there was no mention of drop‐outs or exclusions
Selective reporting (reporting bias)	Unclear risk	Comment: outcomes seem to be reported as stated in the methods section, except for CT scan score where it was stated that all groups showed improvement compared to the saline group. There was no description in the methods about how adverse events were to be collected.
Other bias	Unclear risk	Quote: "The 10‐cm VAS we used consisted of a statistically validated questionnaire that the patient filled out, answering the question 'how troublesome are your symptoms of rhinosinusitis?' is used. The answers range from 0 (not troublesome) to 10 (worst thinkable troublesome)" Comment: they did not fully report how scores were added up and analysed