Study Evaluating the Efficacy and Safety of Intranasal Administration of OPN-375 in Subjects With Chronic Rhinosinusitis With or Without the Presence of Nasal Polyps
- Conditions
- Chronic Rhinosinusitis
- Interventions
- Drug: OPN-375
- Registration Number
- NCT03781804
- Lead Sponsor
- Optinose US Inc.
- Brief Summary
This is a 24-week randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of intranasal administration of 186 and 372 μg twice daily (BID) of OPN-375 in subjects with chronic rhinosinusitis (CS) with or without nasal polyps.
- Detailed Description
The primary objective of this study is to compare the efficacy of intranasal administration of twice-daily doses of 186 and 372 µg of OPN-375 (fluticasone propionate) with placebo in subjects with chronic rhinosinusitis using the following co-primary endpoints:
1. A change from baseline in symptoms as measured by a composite score of nasal congestion, facial pain or pressure sensation, and nasal discharge (anterior and/or posterior) at the end of Week 4.
2. A change from baseline to Week 24/Early Termination (ET) in the average percent of the volume opacified in the ethmoid and maxillary sinuses.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 332
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description OPN-375 372 μg BID OPN-375 OPN-375 372 μg BID x 24 Weeks Placebo OPN-375 Matching Placebo BID x 24 Weeks OPN-375 186 μg BID OPN-375 OPN-375 186 μg BID x 24 Weeks
- Primary Outcome Measures
Name Time Method Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) at the End of Week 4 4 Weeks Change from baseline to the end of Week 4 in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Baseline, Week 24 Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT. Percent volume opacified can range from 0% to 100%. Outcome measure is the percentage change from percent opacification at baseline to percent opacification at Week 24; therefore, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Defined Timepoint - Subject Symptoms and Functioning as Measured by the Sinonasal Outcome Test - 22-item (SNOT-22) Total Score and Sub Domains Week 24 The SNOT-22 is a subject-completed questionnaire that consists of 22 symptoms and social/emotional consequences of their nasal disorder across several domains including: rhinologic, ear/facial pain, psychological dysfunction, and sleep dysfunction. Total scores range from 0-110. Each item is rated as follows: 0=no problem, 1=very mild problem, 2=mild or slight problem,3=moderate problem, 4=severe problem, 5=problem as bad as it can be.
Change From Baseline in Symptoms as Measured by a Composite Score for Each Symptom of Nasal Congestion, Facial Pain or Pressure Sensation, and Nasal Discharge (Anterior and/or Posterior) Week 12 Change from baseline in average total instantaneous AM scores (evaluation of symptom severity immediately preceding the time of scoring) for each symptom: nasal congestion, nasal discharge (anterior and/or posterior), facial pain/pressure sensation. Baseline scores are the averaged total instantaneous AM scores over the last 7 days of the single blind run in period, and the end of Week 4, scores are averaged over the 7 days from the subject diary. Range of scores for each nasal symptom is 0= none, 1 = mild, 2 = moderate, 3 = severe. Composite score is a sum of the 3 symptom scores and will range from 0 to 9.
Comparison of Health Economic Measures- Percentage of Subjects Who Meet the Minimal Objective Criteria for Surgical Intervention Baseline, Week 24 Percentage of Subjects who meet the minimal objective criteria for surgical intervention
Change in Sense of Smell Scores Measured by AM and PM Diary Symptom Scores 12 Weeks Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours) The sense of smell scored as 0= normal, 1=slightly impaired, 2=moderately impaired, 3=absent. The change reported in the results is calculated by subtracting the score reported at Baseline from the score reported at Visit 4 (Week 12).
Change From Baseline in Nasal Discharge (Anterior and/or Posterior) Measured by AM and PM Diary Symptom Scores 12 Weeks Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.
Change From Baseline in Nasal Congestion Measured by AM and PM Diary Symptom Scores 12 Weeks Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours), The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.
Change in Facial Pain or Pressure Sensation Measured by AM and PM Diary Symptom Scores 12 Weeks Subjects will report both instantaneous (evaluation of symptom severity immediately preceding the time of scoring) and reflective (evaluation of symptom severity over the past 12 hours). The Nasal Symptom Scale scores as 0=none, 1=mild-symptoms clearly present but minimal awareness, and easily tolerated, 2= moderate - definite awareness of symptoms that is bothersome but tolerable, 3 = severe - symptoms that are hard to tolerate, cause interference with activities or daily living.
The value reported in the results is calculated by subtracting the score reported by the patient at Baseline from the score reported by the patient at Visit 4 (Week 12).Change From Baseline to Week 24/Early Termination (ET) in the Average Percent of the Volume Opacified in the Ethmoid and Maxillary Sinuses Among Patient Populations 24 Weeks Change from baseline to Week 24/ET in the average percent of ethmoid and maxillary sinus volume opacified as measured by CT for CRS with Nasal Polyps (NP) and without NP sub-groups and in patients with and without previous sinus surgery. Percent volume opacified can range from 0% to 100%. Outcome measure is percentage change from percent opacification at baseline to percent opacification at Week 24; therefor, change in opacification volume can range from -100% to 100%. For example, if Baseline opacification was 68.22% and Week 24 opacification was 66.11%, then the change would be reported as -2.11%.
Change From Baseline to Week 24/ET in the Lund-Mackay Staging System Total Score Baseline, Week 24 Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for each of the left and right ostiomeatal complex (OMC). The total LM score for a CT scan ranges from 0-24.
Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Ethmoids and Maxillary Sinuses Combined 24 Weeks Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).
The values reported for this outcome are the change in total opacification of the left and right maxillary and ethmoid sinuses (Visit 6 \[Wk 24\] score minus Baseline score). Each visit score can range from a total of 0-12 (sum of 0-2 score assigned for each of left and right maxillary, left and right anterior ethmoid, and left and right posterior ethmoid).Change From Baseline to Week24/ET in the Lund-Mackay Staging System Total Scores for Sinus Pairs Week 24 Lund-Mackay Staging System: Lund-Mackay (LM) system (Lund and Mackay, 1993) assigns to each of 10 sinus cavities (left and right maxillary, anterior ethmoid, posterior ethmoid, sphenoid, and frontal) a score of 0 (no opacification), 1 (partial opacification), or 2 (total opacification), plus a 0-2 score for the ostiomeatal complex (OMC).
Each sinus pair (left and right side) listed below can achieve a total score of 0-4 (sum of 0-2 for each side). The values reported below are calculated by subtracting the total score at Baseline from the total score at Visit 6 (Wk 24).Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Ethmoid Sinus as Measured by CT Scan Assessment Baseline, Week 24 Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Sinus Between the Maxillary and Ethmoid Sinuses as Measured by CT Scan Assessment Among Patient Populations 24 Weeks Percent of sinus volume occupied by disease in the worst sinus between maxillary and ethmoid sinuses for the total population, chronic rhinosinusitis with nasal polyps (CRSwNP) subgroup, chronic rhinosinusitis without nasal polyps (CRSsNP) subgroup, patients with previous sinus surgery subgroup, and without previous surgery subgroup.
Comparison of Health Economic Measures- Percentage of Subjects Approved for Surgery Who no Longer Elect to Undergo a Surgery Week 24 Outcome value presented here is the percent of subjects who are approved for surgery but no longer elect to undergo a surgery. The number of participants analyzed indicates the total number of participants for whom this analysis was completed.
Change From Baseline to Week 24/ET in Average Percent of Sinus Volume Occupied by Disease in the Worst Maxillary Sinus as Measured by CT Scan Assessment Baseline, Week 24 Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System Total Score Baseline, Week 24 Zeinrich Modification of the Lund-Mackay Staging System:
Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% for each sinus. Total score ranges from 0 to 50.Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for Ethmoids and Maxillary Sinuses Combined Baseline, Week 24 Zeinrich Modification of the Lund-Mackay Staging System:
Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% The total score for the combined ethmoids and maxillary sinuses can range from 0-30 (0-5 for each left and right of the anterior ethmoid, posterior ethmoid, and maxillary sinuses). The outcome values presented in the results are determined by subtracting the total score at Baseline from the total score at Week 24.Change in Sleep Quality as Measured by the Pittsburgh Sleep Quality Index (PSQI) 12 Weeks, 24 Weeks The PSQI is a validated, self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate 7 "component" scores (each ranging between 0 and 3): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these 7 components yields 1 global score ranging between 0 and 21. Higher values represent a worse outcome.
Change in Overall Health From Baseline to Week 4 and Week 24/ET as Measured by the Percent of Subjects Improved as Indicated by the Patient Global Impression of Change (PGIC) Week 4, Week 24 Global impression of change will be assessed using a subject-completed PGIC scale range: 1 - Very much improved, 2 - Much improved, 3 - Minimally improved, 4 - No change, 5 - Minimally worse, 6 - Much worse, 7 - Very much worse
Change in the 36-Item Short Form Health Survey Version 2 (SF-36v2) Mental Composite Score (MCS) 24 Weeks Change from baseline to Week 24/ET on the MCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Change in Baseline to Week 24/ET as Measured by the Short-Form 36 Health Survey, Version 2 (SF-36v2) 24 Weeks The SF-36v2 is a multipurpose, 36-item subject-completed validated questionnaire that measures 8 domains of health: physical functioning, role limitations due to physical health (RP), bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The SF-36v2 survey with a 4-week recall will be used. It yields scale scores for each of these 8 health domains , each of which is scored from 0 to 100. Higher scores indicate with a better health status, with 100 representing the highest level of functioning possible.
Change in Baseline to Week 24/ET as Measured by the Euroqol 5-dimension (EQ-5D) Instrument Visual Analogue Scale (VAS) 24 Weeks The EQ-5D consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The outcome measured for this study was the EQ VAS, which records the subject's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflects the subject's own judgement. VAS scores range from 0 (worst health you can imagine) to 100 (best health you can imagine).
Change in Baseline to Week 24/ET as Measured by the Short-Form 6-Dimension (SF-6D) Instrument 24 Weeks The SF-6D is a single health state index derived from the 11 items from the SF-36v2. SF-6D scores range from 0 (worst health state) to 1 (best health state).
Comparison of Health Economic Measures- Percentage of Subjects Indicating That They Are Willing to Consider Sinus Surgery Baseline, Week 24 Percentage of subjects indicating that they are willing to consider Sinus Surgery
Change in Work Productivity From Baseline to Week 24/ET as Measured by the Health and Work Performance Questionnaire (HPQ). 24 Weeks The Health and Work Performance Questionnaire measures work productivity (absenteeism and presenteeism). - Absenteeism is measured in missed work days over the past four weeks (range 0-20); absenteeism is measured in % productivity at work (0-100%), with higher values indicating improved productivity. Values for this outcome are reported as the change in relative absenteeism (the percentage of productivity at work) from baseline to Week 24.
Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Sinus Pairs Baseline, Week 24 Zeinrich Modification of the Lund-Mackay Staging System:
Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100% Each sinus pair (left and right side) listed below can achieve a total score of 0-10 (sum of score on each side). The values reported for this outcome calculated by subtracting the score at Baseline from the score at Visit 6 (Wk 24).Change From Baseline to Week 24/ET in the Zeinrich Modification of Lund-Mackay Staging System for the Worst Sinus Between Maxillary and Ethmoid Sinuses Among Patient Populations Baseline, Week 24 Zeinrich Modification of the Lund-Mackay Staging System:
Zeinrich modified the LM system by creating subdivisions within "partial opacification" and increasing the range of scores to 0-5 based on percent opacification: 0 = 0%, 1 = 1%-25%, 2 = 26%-50%, 3 = 51%-75%, 4 = 76%- 99%, and 5 = 100%Time Comparison to First Acute Exacerbation of Chronic Sinusitis 24 Weeks Comparing the distribution of time to first acute exacerbation of chronic sinusitis, defined as a worsening of symptoms that requires escalation of treatment
Percentage of Subjects Requiring Rescue Medication After Week 4 8 Weeks Recording of each dose of approved rescue medication after the Week 4 visit through Week 12
Severity of Depression at Week 24 as Measured by the Quick Inventory of Depression Symptomatology (QIDS) Week 24 The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, where higher scores indicate a worse outcome.
Change in the SF-36v2 Physical Composite Score (PCS) 24 Weeks Change from baseline to Week 24/ET on the PCS of the 36-Item Short Form Health Survey version 2 (SF-36v2). The SF-36v2 is a multipurpose, scaled, 36-item, subject-completed validated questionnaire. The scale range is from 0-100. A lower score means more disability and a higher score means less disability.
Change in Depressive Symptoms From Baseline to Week 24/ET as Measured by Change in the Severity of Depression as Measured by the Quick Inventory of Depression Symptomatology (QIDS) 24 Weeks The 16-item QIDS (Rush et al. 2003) is designed to assess the severity of depressive symptoms. The QIDS is available in a self-rated version and assesses all the criterion symptom domains designated by the American Psychiatry Association Diagnostic and Statistical Manual of Mental Disorders - 5th edition to diagnose a major depressive episode. The 7-day period prior to assessment is the usual time frame for assessing symptom severity. Scores range from 0 to 27, with higher scores indicating a worse outcome.
Change in Olfactory Impairment From Baseline to Week 24/ET as Measured by the Smell Identification Test (SIT)™ 24 Weeks The SIT is a test comprised of 4 booklets each containing 10 microencapsulated (scratch and sniff) odors. Forced choice response alternatives to identify the odor accompany each test item. Each correct response is assigned a score of 1 and incorrect responses are assigned a score of 0. The total score is calculated by summing the scores of each individual odor for a total possible score ranging from 0-40. The higher the score, the better the individual's sense of smell. The test provides an absolute indication of smell loss (anosmia; mild, moderate or severe hyposmia) as well as an index to detect malingering.
Trial Locations
- Locations (92)
Emory University MOT
🇺🇸Atlanta, Georgia, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
John Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Przychodnia "Narutowicza"
🇵🇱Inowrocław, Poland
NZOZ "Ignis" dr med. Alicja Łobińska
🇵🇱Świdnik, Poland
University of TX Health Science Ctr at Houston
🇺🇸Houston, Texas, United States
Jonathan Corren, MD, Clinical Research Division
🇺🇸Los Angeles, California, United States
Sacramento Ear, Nose & Throat
🇺🇸Roseville, California, United States
UC Davis Medical Center
🇺🇸Sacramento, California, United States
Allergy and Asthma Associates of Santa Clara Valley
🇺🇸San Jose, California, United States
St. Cloud Ear, Nose & Throat
🇺🇸Saint Cloud, Minnesota, United States
The University of Chicago
🇺🇸Chicago, Illinois, United States
Allergy & Asthma Clinical Research
🇺🇸Walnut Creek, California, United States
Atlantic Research Center
🇺🇸Ocean City, New Jersey, United States
Colorado ENT & Allergy
🇺🇸Colorado Springs, Colorado, United States
Kern Research
🇺🇸Bakersfield, California, United States
AZ Allergy & Immunology Research
🇺🇸Gilbert, Arizona, United States
Allergy & Asthma Specialists Medical Group
🇺🇸Huntington Beach, California, United States
Breathe Clear Institute
🇺🇸Torrance, California, United States
University of Missouri, Dept of Otorlaryngology
🇺🇸Columbia, Missouri, United States
Sacramento Ear, Nose & Throat Surgical and Medical Group Inc
🇺🇸Folsom, California, United States
Kentuckiana Ear Nose & Throat
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Iowa Head & Neck
🇺🇸Des Moines, Iowa, United States
Medicus Sp z o.o.
🇵🇱Wrocław, Dolnoslaskie, Poland
NZOZ Imedica
🇵🇱Poznań, Wielkopolska, Poland
Multiprofile Hospital for Active Treatment Serdika
🇧🇬Sofia, Bulgaria
Specialty Physician Associates
🇺🇸Bethlehem, Pennsylvania, United States
Mount Sinai Downtown Union Square
🇺🇸New York, New York, United States
The Military Medical Academy (MHAT)
🇧🇬Sofia, Bulgaria
Bellingham Asthma, Allergy & Immunology Clinic
🇺🇸Bellingham, Washington, United States
National Allergy and Asthma Research
🇺🇸North Charleston, South Carolina, United States
Hospital at the University of PA
🇺🇸Philadelphia, Pennsylvania, United States
Midwest Allergy Sinus Asthma
🇺🇸Normal, Illinois, United States
Jarosław Ślifirski Indywidualna Praktyka Lekarska
🇵🇱Kęty, MA, Poland
NZOZ Centrum Medyczne LiMED
🇵🇱Tarnowskie Góry, SL, Poland
Medical Center Woś i Piwowarczyk
🇵🇱Kraków, Poland
NZOZ Przychodnia Medycyny Rodzinnej
🇵🇱Świętochłowice, Poland
ONH Kliniken Sahlgrenska Universitetsynkhiset
🇸🇪Gothenburg, Vastra Gotaland Lan, Sweden
Advanced ENT and Allergy
🇺🇸New Albany, Indiana, United States
Wrightington, Wigan and Leigh NHS Foundation Trust
🇬🇧Wigan, United Kingdom
Мinistry of Interior - Medical Institute
🇧🇬Sofia, Bulgaria
University Hospital of Wales
🇬🇧Cardiff, Cf14 4xw, United Kingdom
Mini Clinic Paweł Białogłowski
🇵🇱Łańcut, PK, Poland
Sofiahemmet Hospital
🇸🇪Stockholm, Sweden
CHU de Quebec, pavillon Hopital Saint- Sacrement
🇨🇦Québec, Canada
Madison ENT and Facial Plastic Surgery
🇺🇸New York, New York, United States
Centrum Medyczne Biotamed
🇵🇱Wieliczka, Malopolskie, Poland
Darlington Memorial Hospital
🇬🇧Darlington, United Kingdom
Allergy Asthma & Immunology Relief of Charlotte
🇺🇸Charlotte, North Carolina, United States
Centrum Medyczne All Med - Krakow
🇵🇱Kraków, Poland
Holston Medical Group
🇺🇸Kingsport, Tennessee, United States
Ltd Simon Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
Stockport NHS Foundation Trust (Stepping Hill Hospital Base)
🇬🇧Stockport, United Kingdom
St. Joseph's Healthcare London
🇨🇦London, Ontario, Canada
Ltd Acad. Fridon Todua Medical Center
🇬🇪Tbilisi, Georgia
JSC Curatio
🇬🇪Tbilisi, Georgia
Ltd Aversi Clinic
🇬🇪Tbilisi, Georgia
ReumaClinic
🇵🇱Białystok, Poland
Centrum Medyczne Lucyna Andrazej Dymek - Strzelce Opolskie
🇵🇱Strzelce Opolskie, Poland
UMHAT - Kaspela EOOD
🇧🇬Plovdiv, Bulgaria
Saint-Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺Saint Petersburg, Saint-Petersburg, Russian Federation
Karolinska University Hospital
🇸🇪Stockholm, Stockholms Lan, Sweden
MC Iskar
🇧🇬Sofia, Bulgaria
MC Pirogov
🇧🇬Sofia, Bulgaria
Lister Hospital
🇬🇧Stevenage, United Kingdom
STAAMP Research, LLC
🇺🇸San Antonio, Texas, United States
University of British Columbia and Providence Health Care
🇨🇦Vancouver, British Columbia, Canada
Helsingborg Hospital
🇸🇪Helsingborg, Sverige, Sweden
Ear, Nose and Throat Associates at Greater Baltimore Medical Center
🇺🇸Towson, Maryland, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Yale School of Medicine Section of Otolaryngology
🇺🇸New Haven, Connecticut, United States
Asthma, Allergy, and Immunology Associates, PC
🇺🇸Lincoln, Nebraska, United States
ENT and Allergy Associates
🇺🇸New Hyde Park, New York, United States
Vital Prospects Clinical Research Institute, P.C.
🇺🇸Tulsa, Oklahoma, United States
Northwest Research Center
🇺🇸Portland, Oregon, United States
Eastern Virginia Medical School
🇺🇸Norfolk, Virginia, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Intermountain Ear, Nose & Throat
🇺🇸Salt Lake City, Utah, United States
Ltd Israel-Georgian Medical Research Clinic - Helsicore
🇬🇪Tbilisi, Georgia
Moscow Regional Scientific Research Clinical Institute n.a. M.F. Vladimirsky (MONIKI)
🇷🇺Moscow, Moskovskaya Obl., Russian Federation
I.M. Sechenov First Moscow State Medical University-University Hospital No.1 - Ear, Nose, and Throat Clinic
🇷🇺Moscow, Moskovskaya Obl., Russian Federation
ONH Klinikun Skane Universitetssjukhuset (Lund - Oron- Nas- Och Halskliniken)
🇸🇪Lund, Skane Lan, Sweden
Smolensk, "Uromed"
🇷🇺Smolensk, Smolenskaya Obl, Russian Federation
Yaroslavl Regional Clinical Hospital
🇷🇺Yaroslavl, Yaroslavskaya Obl., Russian Federation
Allergy Asthma & Clinical Research Center
🇺🇸Oklahoma City, Oklahoma, United States
Chrysallis Clinical Research
🇺🇸Saint George, Utah, United States
Saint-Petersburg Institute of Ear, Nose, Throat, and Speech (The RSFSR Ministry of Health)
🇷🇺Saint Petersburg, Russian Federation
Centrum Alergologii
🇵🇱Lublin, Poland
Centrum Medyczne Angelius Provita
🇵🇱Katowice, SL, Poland
Spokane ENT
🇺🇸Spokane Valley, Washington, United States
Central Clinical Hospital with Polyclinic" Office of Affairs of the President of the Russian Federation
🇷🇺Moscow, Russian Federation