Azithromycin for Patients With Chronic Rhinosinusitis Failing Medical and Surgical Therapy

NCT02307825 | Completed Phase 4 DMC

• 1 other identifier: 14.140
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Rhinosinusitis; High-risk Patient

Keywords

Azithromycin; Endoscopic sinus surgery

Outcome Measures

Primary Outcomes (1)

• Signs and symptoms outcome to Azithromycin

  Evaluate if Azithromycin 250mg by mouth, three times a week for four months will be effective in controlling signs and symptoms of chronic rhinosinusitis patients at a high-risk of recurrence following standard medical and surgical treatment. Disease level is evaluated through nasal endoscopy.

  4 months

Secondary Outcomes (3)

• Treatment algorithm validation

  8 months

• High-risk population

  12 months

• Azithromycin mechanism of action

  12 months

Study Arms (2)

Azithromycin

ACTIVE COMPARATOR

Patients will receive the active study drug, azithromycin, as well as sinus irrigations with budesonide.

Drug: Azithromycin

Placebo

PLACEBO COMPARATOR

Patients will receive a placebo as well as sinus irrigations with budesonide.

Drug: Placebo

Interventions

Azithromycin DRUG

The drug will be taken three times a week for four months.

Also known as: Zithromax

Azithromycin

Placebo DRUG

The placebo will be taken three times a week for four months.

Also known as: No other name

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• Pfizer: collaborator

Study Sites (1)

Centre Hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2W 1T8, Canada

Location

Related Publications (6)

• 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.

  PMID: 24598145 BACKGROUND

• 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.

  PMID: 18444486 BACKGROUND

• 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.

  PMID: 21658337 BACKGROUND

• 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.

  PMID: 20122348 BACKGROUND

• Renteria AE, Maniakas A, Pelletier A, Filali-Mouhim A, Brochiero E, Valera FCP, Adam D, Mfuna LE, Desrosiers M. Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis. Otolaryngol Head Neck Surg. 2023 Dec;169(6):1662-1673. doi: 10.1002/ohn.482. Epub 2023 Aug 25.

  PMID: 37622488 DERIVED

• 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.

  PMID: 32713109 DERIVED

MeSH Terms

Interventions

Azithromycin

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Martin Y Desrosiers, MD, FRCSC

  CHUM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2014
• First Posted: December 4, 2014
• Study Start: November 1, 2014
• Primary Completion: August 15, 2017
• Study Completion: December 31, 2017
• Last Updated: January 26, 2018

Record last verified: 2016-09

Locations

CA (1)