Azithromycin for Patients With Chronic Rhinosinusitis Failing Medical and Surgical Therapy (AZI-CRS)
|ClinicalTrials.gov Identifier: NCT02307825|
Recruitment Status : Completed
First Posted : December 4, 2014
Last Update Posted : January 26, 2018
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.
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Rhinosinusitis High-risk Patient||Drug: Azithromycin Drug: Placebo||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||129 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Azithromycin as add-on Therapy in Patients Failing Medical and Surgical Treatment for Chronic Rhinosinusitis: a Double-blind, Randomized, Placebo-controlled Trial|
|Actual Study Start Date :||November 2014|
|Actual Primary Completion Date :||August 15, 2017|
|Actual Study Completion Date :||December 31, 2017|
Active Comparator: Azithromycin
Patients will receive the active study drug, azithromycin, as well as sinus irrigations with budesonide.
The drug will be taken three times a week for four months.
Other Name: Zithromax
Placebo Comparator: Placebo
Patients will receive a placebo as well as sinus irrigations with budesonide.
The placebo will be taken three times a week for four months.
Other Name: No other name
- Signs and symptoms outcome to Azithromycin [ Time Frame: 4 months ]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.
- Treatment algorithm validation [ Time Frame: 8 months ]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.
- High-risk population [ Time Frame: 12 months ]
Characterise and define the population deemed "high-risk" for standard CRS treatment failure by evaluating:
- The demographics of this population
- The inflammatory state of patients at the different follow-ups (serum biomarkers)
- The microbiome of the nasal flora of patients at the different follow-ups (microbial cultures)
- Azithromycin mechanism of action [ Time Frame: 12 months ]Explore the mechanisms of action of AZI by assessing the changes in inflammatory states (serum biomarkers and epithelium inflammation) and the nasal flora microbiome (microbial cultures) associated with successful AZI therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02307825
|Centre Hospitalier de l'Université de Montréal (CHUM)|
|Montreal, Quebec, Canada, H2W 1T8|
|Principal Investigator:||Martin Y Desrosiers, MD, FRCSC||CHUM|