Weschta 2004.
| Methods | 2‐arm, double‐blind, single‐centre, parallel‐group RCT, with 8 weeks duration of treatment and follow‐up | |
| Participants |
Location: Germany, 1 site Setting of recruitment and treatment: Department of Otorhinolaryngology and Head and Neck Surgery Sample size: 78
Participant (baseline) characteristics:
Inclusion criteria: 1)age > 18 years, 2) recent CT scan of paranasal sinuses, 3) symptom score > 14 (max 30), 4) endoscopy score > 2 (max 6), 5) CT score > 19 (max 40) Exclusion criteria: 1) current participation in other clinical study, 2) pregnancy or breast‐feeding, 3) mental impairment or severe illnesses, 4) hypersensitivity to study medication, 5) history of immotile cilia syndrome or cystic fibrosis, 6) urgent need for or recent paranasal surgery, 7) recent start on specific antiallergic immunotherapy, corticosteroid therapy, antihistamines, acetylsalicylic acid desensitisation, 8) discontinuous study medication intake, 9) antimycotic or immunosuppressive therapy, 9) clinical suspicion of AFRS |
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| Interventions |
Intervention (n = 39): amphotericin B (3 mg/mL), nasal spray, 2 puffs per nostril (200 µL per nostril), 4 times daily. Total daily dose = 4.8 mg amphotericin. Treatment duration = 8 weeks. Comparator group (n = 39): control nasal spray: saline solution containing tartrazine, chinin sulfate, 1‐(4‐sulfo‐1‐phenylazo)‐2‐naphthol‐6‐sulfo acid, choline in 5% glucose solution, 2 puffs per nostril, 4 times daily. Treatment duration = 8 weeks. Use of additional interventions (common to both treatment arms): Patients were allowed to continue with medication as before providing the dose was stable. Topical or systemic corticosteroids were used by 61% in the intervention and 50% in the control group. |
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| Outcomes |
Outcomes of interest in the review: Primary outcomes:
Secondary outcomes:
Other outcomes reported by the study:
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| Funding sources | No information provided | |
| Declarations of interest | No information provided | |
| Notes | — | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "Patients were randomly allocated to the 2 treatment arms by the Department of Biometry and Medical Documentation, University of Ulm." Comment: no further information provided about method of randomisation |
| Allocation concealment (selection bias) | Unclear risk | Comment: no mention of methods used to conceal allocation of patients. It does mention that healthcare professionals were kept blind to the treatment allocation until the end of the study. |
| Blinding of participants and personnel (performance bias) All outcomes | Low risk | Quote: "Active drug and control sprays were manufactured by the pharmacy of the University Hospital of Ulm. They were indistinguishable in color, taste, smell, and nasal sensations during application." "To assure blinding of investigators, the mild irritant chinin sulfate was added to the control spray. Neither patients nor investigators were aware of the kind of treatment during the entire study period." |
| Blinding of outcome assessment (detection bias) All outcomes | Low risk | Comment: although this is not discussed in detail, the flow chart on page 1124 clearly shows that "unblinding" occurred after the data analysis was completed |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Comment: 15/39 (38%) participants dropped out from the intervention arm; 7/39 (18%) dropped out of the control arm. Reasons for the dropouts were provided; most in the intervention group were due to intolerance of the study medication |
| Selective reporting (reporting bias) | Unclear risk | Comment: the protocol for the study could not be identified through clinicaltrials.gov or the European trials registry. All of the outcomes as reported in the methods section were reported in the results section although for some only vague figures are given. For example, for endoscopic score the paper states "The median endoscopy scores were almost identical in the AMB and control groups (4 vs 4) and did not change remarkably after treatment." A big difference in adverse effects between the groups is reported but details of the events and the number of patients is not provided. |
| Other bias (non‐validated instrument) | Unclear risk | Comment: for disease‐specific quality of life the study modified an existing questionnaire developed for patients with allergy ‐ the mini Rhinoconjunctivitis Quality of Life Questionnaire (mRQLQ) "rhinosinusitis quality of life score (RQL)". However, the paper does not provide any link to any validation of the modified instrument, and no publications on the validation of the RQL were found by the review authors. The remaining instruments used were well‐accepted, validated instruments (Lund Mackay, VAS used for symptoms). |
| Other bias | Unclear risk | Comment: baseline characteristics were balanced with the exception of gender. The procedure for additional recruitment of patients to compensate for dropouts was not reported. |
AFRS: allergic fungal rhinosinusitis ALT: alanine aminotransferase AMB: amphotericin B ARS: acute rhinosinusitis AST: aspartate aminotransferase CT: computerised tomography CRS: chronic rhinosinusitis ENT: ear, nose and throat ESS: endoscopic sinus surgery F: female GGT: gamma‐glutamyl transpeptidase IM: intramuscular LAS: lysine acetylsalicylate M: male NP: nasal polyps RANTES: regulated on activation, normal T cell expressed and secreted RCT: randomised controlled trial RSOM‐31: Rhinosinusitis Outcome Measure‐31 SD: standard deviation SNOT‐20: Sino‐Nasal Outcome Test‐20 VAS: visual analogue scale WHO: World Health Organization