Chronic rhinosinusitis MedDRA version: 20.0 Level: LLT Classification code 10052106 Term: Rhinosinusitis System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: PT Classification code 10009137 Term: Chronic sinusitis System Organ Class: 10021881 - Infections and infestations MedDRA versio
Conditions
Interventions
Trade Name: Clarithromycin
Product Name: Clarithromycin
Pharmaceutical Form: Capsule
INN or Proposed INN: Clarithromycin
CAS Number: 811
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Adults aged 18 and over with a diagnosis of CRS according to European guidelines: *A minimum of 12 weeks history of inflammation of the nose and paranasal sinuses characterised by two or more symptoms, one of which should be either nasal blockage/obstruction/ congestion or nasal discharge (anterior/posterior nasal drip): - ± facial pain/pressure - ± reduction or loss of smell • Nasal endoscopy (within last 3 months) to determine CRS diagnosis and phenotype (CRSwNPs or CRSsNPs) • Non-contrast CT scan (within last 12 months) to determine Lund-Mackay score and confirm suitability for ESS • Moderate/severe symptoms; SNOT-22 score = 20 within last 3 months • Symptom control not achieved following previous AMT, as deemed by the local Principal Investigator (PI) or Co-Investigator (Co-I), and therefore considered eligible for ESS • An understanding of the English language sufficient to understand written and verbal information about the trial, its consent process and the study questionnaires Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: • Lund-Mackay non-contrast CT scan score 3 continuous weeks’ duration within the last 12 months • ESS in previous 6 months or visible, open sinus cavities from previous surgery • Maintenance oral steroids or biologics • Rare/complex sinus conditions: *CRS secondary to systemic disease - cystic fibrosis, granulomatous diseases *Suspected malignancy • Allergic fungal rhinosinusitis confirmed or suspected on CT imaging (expansion and mixed density opacification) necessitating immediate surgery • Severe asthma (high doses of inhaled steroids i.e. >1.5mg per day) • Females who are pregnant or breastfeeding, females of reproductive potential not prepared to use a reliable means of contraception (e.g. hormonal contraceptive patch, intrauterine device, physical barrier or abstinence, if preferred and usual lifestyle of the patient) at trial entry or those females wanting to start a family during the initial 3 months of the trial • Known immunodeficiency states including HIV and selective and multiple antibody deficiency states • Severe septal deviation preventing endoscopic examination • Contraindications to surgery (significant medical co-morbidity) • Any absolute contraindications to clarithromycin (risk factors to be assessed at screening include history of ischaemic heart disease, prolonged Q-T interval on ECG, diabetes and age over 65 or any medications known to interact with clarithromycin unless these can be discontinued during the 3 months of clarithromycin/placebo treatment) • Known allergies to the IMP and excipients of IMP and placebo • Inability to give consent (significant cognitive impairment or language issues), or to understand and comply with trial instructions • Participation in another Randomized Clinical Trial in the past 4 months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the comparative effectiveness of a prolonged course of antibiotics (clarithromycin) or endoscopic sinus surgery (ESS) in adult patients with CRS in terms of symptomatic improvement and costs to the NHS and patients, compared with standard medical care and each other at six months.; Secondary Objective: • Measure clinical effectiveness using subjective self-reporting ratings and objective clinical measures • Compare the clinical effectiveness according to phenotype (CRSwNPs/CRSsNPs) • Record the incidence and details of adverse events in all treatment arms related to the trial medication or surgery intervention • Establish the cost effectiveness and cost utility over the 6 month trial duration • Embed a mixed methods evaluation into the main trial to identify factors and processes necessary for implementation of trial findings Internal recruitment pilot phase objectives • To randomise 72 participants at 6 pilot sites within 6 months. Recruitment will be deemed successful if =75% of expected, i.e. 54 patients are recruited • Undertake a MACRO Conversation Study (using qualitative methods) during the pilot phase to identify recruitment challenges and optimize recruitment during the main trial phase. ;Primary end point(s): Disease-specific health related quality of life (HRQoL) using the SNOT-22 Patient Reported Outcome Measure (PROM) Questionnaire at six months;Timepoint(s) of evaluation of this end point: Baseline, 6 weeks, 3 and 6 months. Those participants who opted to be followed-up on a long term basis will be contacted annually for a further 5 years after completing the trial. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Endoscopic score, including grade of polyps (0 – 3) if present (Lund-Kennedy Score) • Health-related quality of life and quality-adjusted life-years (QALYs), measured by the SF-12 and EQ-5D-5L questionnaires • Need for rescue oral steroids or antibiotic use for acute exacerbations, recorded by patient diaries • Olfactory function measured using Sniffin’ Sticks • Upper and lower respiratory function, measured using peak expiratory flow rate, peak nasal inspiratory flow rate • Treatment needed to control symptomatic reversible airway disease, measured using the Asthma Control Test • Adverse effects of treatment and readmissions relating to allocated treatment • Healthcare resource use, including medications and visits to primary and secondary care, recorded using patient diaries • Days of work missed, recorded using patient diaries • Overall cost and incremental cost per quality-adjusted life-year gained, from the cost perspective of the NHS and PSS, calculated using quality of life scores • Budget impact of treatment ;Timepoint(s) of evaluation of this end point: Baseline, weekly, 6 weeks, 3 and 6 months. Those participants who opted to be followed-up on a long term basis will be contacted annually for a further 5 years after completing the trial. | — |
Countries
United Kingdom
Contacts
Public ContactSteffi le Conte
University of Oxford
Outcome results
None listed