Clinical trial NCT02307825: Azithromycin for Patients With Chronic Rhinosinusitis Failing Medical and Surgical Therapy
Official title: Azithromycin as add-on Therapy in Patients Failing Medical and Surgical Treatment for Chronic Rhinosinusitis: a Double-blind, Randomized, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Rhinosinusitis
High-risk Patient
Keywords: Azithromycin
Endoscopic sinus surgery
Lead sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2014-12-04
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Justification: Chronic rhinosinusitis (CRS) is one of the most common inflammatory diseases with an incidence and prevalence superior to 10%. Unfortunately, more than 30% of patients do not respond to standard medical and surgical treatment, thus continuously increasing the symptomatologic and socio-economic burden of this disease.

Hypothesis: The investigators believe that the addition of azithromycin (AZI) to the treatment regimen of patients with refractory CRS failing conventional medico-surgical treatment will be beneficial in a symptomatologic and endoscopic level.

Primary objective: 1- To evaluate whether Azithromycine 250 mg PO three times weekly is effective in controlling signs and symptoms of CRS in high-risk patients unresponsive to standard management after endoscopic sinus surgery (ESS) with budesonide irrigations.

Secondary objectives:

i) Validate a simple and concise treatment algorithm for patients refractory to standard CRS treatment of ESS and BUDI, with the addition of low-dose AZI.

ii) Characterise and define the population deemed "high-risk" for standard CRS treatment failure by evaluating: 1) demographics, 2) inflammatory states and 3) the nasal flora microbiome of patients at the different follow-up points of this study.

iii) Explore the mechanisms of AZI by assessing the changes in inflammatory states and the nasal flora microbiome associated with successful AZI therapy.

Methods: Inclusion of all patients admitted for endoscopic sinus surgery (ESS) for CRS operated by the same surgeon (MD). Following their first postoperative visit (2 weeks), all patients will receive nasal irrigations with budesonide (BUDI) twice daily for 4 months and will be re-evaluated. If there is a failure of treatment, patients eligible to receive AZI will be randomized in to two groups, AZI 250mg or a placebo three times a week for 4 months. At every follow-up, complete endoscopic exams will be performed, along with sinus cultures and brush cytology.

Population: All patients deemed "high-risk" with CRS admitted for ESS between October 2014 and October 2015.


Eligibility criteria: Inclusion Criteria:

Patients with ≥1 of the following criteria:

* history of sinus surgery,
* first sinus surgery at ≤38 years of age,
* an absolute eosinophilia of ≥500 cells/mm,
* serum IgE levels of \>150 kIU/L,
* a Gram negative bacteria in a sinus culture,
* the presence of intra-operative eosinophilic mucin.

Exclusion Criteria:

* Patients with cystic fibrosis, inverted papillomas, osteomata, mucoceles or other lesions of the base of skull will be excluded.
* Patients with an elevated cardiovascular disease risk will be excluded from the randomized clinical trial part of this study.

Primary outcomes:
measure: Signs and symptoms outcome to Azithromycin
timeFrame: 4 months
Secondary outcomes:
measure: Treatment algorithm validation
timeFrame: 8 months
measure: High-risk population
timeFrame: 12 months
measure: Azithromycin mechanism of action
timeFrame: 12 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Centre Hospitalier de l'Université de Montréal (CHUM)
state: Quebec
Study officials:
affiliation: CHUM
name: Martin Y Desrosiers, MD, FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maniakas A, Desrosiers M. Azithromycin add-on therapy in high-risk postendoscopic sinus surgery patients failing corticosteroid irrigations: A clinical practice audit. Am J Rhinol Allergy. 2014 Mar-Apr;28(2):151-5. doi: 10.2500/ajra.2013.27.4017. Epub 2013 Dec 13.
citation: Desrosiers MY, Kilty SJ. Treatment alternatives for chronic rhinosinusitis persisting after ESS: what to do when antibiotics, steroids and surgery fail. Rhinology. 2008 Mar;46(1):3-14.
citation: Desrosiers M, Evans GA, Keith PK, Wright ED, Kaplan A, Bouchard J, Ciavarella A, Doyle PW, Javer AR, Leith ES, Mukherji A, Robert Schellenberg R, Small P, Witterick IJ. Canadian clinical practice guidelines for acute and chronic rhinosinusitis. J Otolaryngol Head Neck Surg. 2011 May;40 Suppl 2:S99-193. English, French.
citation: Nader ME, Abou-Jaoude P, Cabaluna M, Desrosiers M. Using response to a standardized treatment to identify phenotypes for genetic studies of chronic rhinosinusitis. J Otolaryngol Head Neck Surg. 2010 Feb;39(1):69-75.
citation: Renteria AE, Maniakas A, Mfuna LE, Asmar MH, Gonzalez E, Desrosiers M. Low-dose and long-term azithromycin significantly decreases Staphylococcus aureus in the microbiome of refractory CRS patients. Int Forum Allergy Rhinol. 2021 Feb;11(2):93-105. doi: 10.1002/alr.22653. Epub 2020 Jul 26.