Cystic FibrosisPhase 3AVASMUCNCT02888730
Tobramycin Delivered by Nebulized Sonic Aerosol for Chronic Rhinosinusitis Treatment of Cystic Fibrosis Patients
A Phase 3 study testing Tobramycin nebulized nasally and Physiologic serum nebulized nasally in people with Cystic Fibrosis and Rhinosinusitis, run by Virginie ESCABASSE at 6 sites in France.
Trial summary
Patients with cystic fibrosis frequently develop chronic rhinosinusitis. Bacterial colonization is facilitated by a reduced mucociliary function and some previous studies suggest that the microbiology of the upper airways might influence the microbiology of the lower airway. Read more about this study
- Who is it for?
- Ages 7 years and older
- Conditions the study is for
- Cystic Fibrosis, Rhinosinusitis, Lung Diseases
- What is being tested?
- Tobramycin nebulized nasally and Physiologic serum nebulized nasally
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 6 sitesFrance
- Study dates
- 16 Feb 2017to 8 Jul 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients older than 7 years followed in the 6 CRCM centers (Créteil, Marseille, Nantes, Toulouse, Clermont-Ferrand and Nice). We choose to enroll children aged 7 years or more because as they have a better adherence to nebulization treatment than younger children.
- Diagnosis of cystic fibrosis confirmed by sweat test (>60mmol/L) and/or the identification of two CF-causing mutations
- Confirmed chronic rhinosinusitis by Ear Nose and Throat doctor by endoscopic examination: bilateral mucopurulent secretions at middle meatus present longer than 12 weeks with or without nasal polyps
- Positive bacteria susceptibility to tobramycin in samples from middle meatus
- Susceptibility of bacteria to tobramycin confirmed
- Pulmonary examination before enrollment
- Written informed consent obtained at enrollment for all patients (consent of minor's parent for children)
- Social security affiliation
Who cannot join
- - Oral antibiotic therapy one month before enrollment
- enrollment in another protocol with antibiotic
- Ongoing aerosolized tobramycin for endobronchial infection to avoid an overlap between treatment for lung and treatment for sinusitis
- Abnormal auditory acuity (decrease of 20dB in auditory acuity)
- Hypersensibility or allergenecity of aminoglycosides
- FEV < 25% or FVC of 40% or more of the value predicted for height
Show all 12Show fewer
- Transplant patient or patient on transplant list
- Patient under nasal oxygen or under noninvasive ventilation
- Pregnant woman
- Breast-feeding
- No Social security affiliation
- Informed consent non obtained at enrollment for all patients (consent of minor's parent for children)
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
Centre Hospitalier Universitaire de Clermont ferrand
Clermont-Ferrand, 63003
Centre Hospitalier Intercommunal de Créteil
Créteil, 94000
Centre Hospitalier Universitaire de la Timone
Marseille, 13385
Centre Hospitalier Universitaire De Nantes
Nantes, 44093
Centre Hosiptalier de Nice
Nice, 06002
Centre Hospitalier Universitaire de Toulouse
Toulouse, 31059
About this study
Official title: Efficacy of Antibiotic (Tobramycin) Delivered by Nebulized Sonic Aerosol for Chronic Rhinosinusitis Treatment of Cystic Fibrosis Patients: A Multicenter Double-blind Randomized Controlled Trial
Patients with cystic fibrosis frequently develop chronic rhinosinusitis. Bacterial colonization is facilitated by a reduced mucociliary function and some previous studies suggest that the microbiology of the upper airways might influence the microbiology of the lower airway. The aim of this randomized control study is to demonstrate efficacy of antibiotic delivered by nebulized sonic aerosol therapy to decrease the bacterial load in sinuses and medium ostia and to improve the sino-nasal symptoms and endoscopic scores, quality of life and lung function
Read the detailed description
Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in the Caucasian population affecting ~1:3000 children, with a carrier frequency of 1:25. It is a multisystem disorder where pulmonary and sinonasal involvements occur in 90-100% of patients, and up to 86% of children have nasal polyps . Patients with CF develop chronic rhinosinusitis (CRS) due to the defect in the cystic fibrosis Transmembrane Regulator (CFTR) protein. The membrane lining the paranasal sinuses and the nose is identical to the membrane lining the lungs. As in lower airways (LAW) the defect CFTR protein result in viscous mucus . Consequently mucociliary function is reduced, which facilitates bacterial colonization and eventually infection leading to rhinosinusitis . In the past decades infection of the lower airways was the most prominent focus in treatment protocols for CF. Over the years infection of the upper airways (UAW) gradually gained more attention in CF.
Previous research in the microbiology of the upper airways (UAW) in CF displayed that Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus were most frequently cultures from the UAW . Since several studies showed concordance between organisms in the UAW and the LAW in CF, the hypothesis evolved that the UAW might influence the patient pulmonary status . Moreover, comparison of UAW and and LAW cultures in CF adult patients showed that Pseudomonas aeruginosa can be cultured from the UAW after eradication therapy which may suggest persistence of Pseudomonas aeruginosa in the UAW . This problem is highlighted in double lung transplant where UAW also appears as a protective niche of adapted clones of bacteria, which can intermittently spread this pathogen to the lung.
CRS treatment in CF patients is based on daily nasal lavages but above all on local or systemic antibiotic treatments to eradicate bacteria in sinuses . Local therapy is favoured in CRS treatment of CF patients to avoid antibiotic side effects, changing organisms or resistance patterns. Sonic aerosol therapy with antibiotics for 15 days is commonly used for CRS in non CF patients to improve sinonasal symptoms and reduce purulent secretions as sound addition in pneumatic aerosol in head corpse's models creates an acoustic pressure at the ostia to improve the aerosol penetration in maxillary sinuses . However its efficacy on bacterial carrying in sinuses is not proved . At the opposite, efficacy of aerosol of tobramycin to LAW was proved in CF patients with a decrease of the density of Pseudomonas aeruginosa, an improvement of FEV, and fewer pulmonary exacerbations .
At the present time, efficacy of antibiotic (tobramycin) delivered by nebulized sonic aerosol for CRS treatment of CF patients is unknown particularly on bacterial carrying.
The aim of this study is to demonstrate that nebulized sonic aerosol therapy with tobramycin in Cystic Fibrosis patients decreases significantly bacterial carrying in sinuses, sinus ostia of middle meatus and sputum compared to nebulized sonic aerosol therapy with placebo and that nebulized sonic aerosol therapy improves sino-nasal symptoms and endoscopic scores, quality of life and lung function.
- Conditions
- Cystic Fibrosis, Rhinosinusitis, Lung Diseases
- Being tested
- Tobramycin nebulized nasally, Physiologic serum nebulized nasally
- Keywords
- cystic fibrosis, chronic rhinosinusitis, Lung Diseases, tobramycin, nebulized sonic aerosol therapy
- Medical subject headings
- Cystic Fibrosis, Rhinosinusitis, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tobramycin nebulized nasallyDrug
Also called Tobramycin
Two sonic nebulizations per day will be realized by patients: morning and evening during 15 days. There should be a maximum of 12 hours between the 2 doses but shall not be less than 6 hours. The dosage should not be adjusted to body weight. All patients will receive one ampoule of tobramycin twice a dayAmpoules of tobramycin are filled by 5 ml containing 300 mg of tobramycin and 11.25 mg of sodium chloride. Bulb should be employed in nebulizer and administered by the inhalation route approximately 15 minutes to complete.Antibiotic retained for the study, tobramycin is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital. The study's product will be prepared with Base Tobramycin and excipients in accordance with TOBI's composition.
Physiologic serum nebulized nasallyDrug
Also called sodium chloride 0.9%
Two sonic nebulizations per day will be realized by patients: morning and evening during 15 days. There should be a maximum of 12 hours between the 2 doses but shall not be less than 6 hours. The dosage should not be adjusted to body weight. All patients will receive one ampoule of placebo (Nacl 0.9%) twice a day.Ampoules of placebo are filled by 5 ml containing of sodium chloride. Bulb should be employed in nebulizer and administered by the inhalation route approximately 15 minutes to complete. Placebo for the study is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital. Patients in placebo arm will receive 5ml of sodium chloride with the same color (light yellow transparent) as tobramycin
| Study group | Role | What they receive |
|---|---|---|
| Tobramycin nebulized nasally | Experimental | Nebulized Tobramycin, one bulb (tobramycin 300 mg and sodium chloride 11.25 mg) nasally twice a day for 15 days Receives: Drug: Tobramycin nebulized nasally |
| Physiologic serum nebulized nasally | Placebo comparator | Nebulized sodium chloride 0.9%, one bulb twice a day nasally for 15 days Receives: Drug: Physiologic serum nebulized nasally |
What is being measured
The primary outcome is the main question the study is designed to answer.
Density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 15
Measured: 15 days
Secondary outcomes (14)
density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 30 and 90
Measured: day 30 and day 90
Minimum inhibitor concentration of sputum bacteria to antibiotics
Measured: day 15, 30 and 90
Minimum inhibitor concentration of sputum bacteria to tobramycin
Measured: day 90
Force Vital capacity (FCV) in both groups
Measured: day 0 and day 30
Forced Expiratory Volume in one second (FEV1) in both groups
Measured: day 0 and day 30
nasal obstruction at day 90 compared to baseline
Measured: day 0, 15, 30 and 90
rhinorrhea compared to baseline
Measured: day 0, 15, 30 and 90
mucopurulent secretions compared to baseline
Measured: day 0, 15, 30 and 90
facial pain compared to baseline
Measured: day 0, 15, 30 and 90
dysosmia compared to baseline
Measured: day 0, 15, 30 and 90
Nasal endoscopic scores compared to baseline in both groups
Measured: day 0, 15, 30 and 90
Score of the SM5 quality of life questionnaire in both groups
Measured: day 0, 15, 30 and 90
Score of the SNOT20 quality of life questionnaire in both groups
Measured: day 0, 15, 30 and 90
Hearing perception of the intensity (in db) and tone (Hz) of sound waves
Measured: day 0 and day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2016 (estimated)
- Study start16 Feb 2017
- Primary completion16 May 2017
- Study completion8 Jul 2019
Why it stopped: No suffisant recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginie ESCABASSE
- Sponsor type
- University, hospital or other
- Collaborators
- Henri Mondor University Hospital
- Responsible party
- Sponsor-investigator, Virginie ESCABASSE, Centre Hospitalier Intercommunal Creteil
- Investigators
- Virginie Escabasse, MD, Principal investigator, Creteil Hospital center (CHIC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02888730
- Sponsor's protocol ID
- AVASMUC
- Acronym
- AVASMUC
- Status last verified
- Feb 2023
- First submitted
- 22 Jun 2016
- Last updated
- 15 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Aanaes K, von Buchwald C, Hjuler T, Skov M, Alanin M, Johansen HK. The effect of sinus surgery with intensive follow-up on pathogenic sinus bacteria in patients with cystic fibrosis. Am J Rhinol Allergy. 2013 Jan;27(1):e1-4. doi: 10.2500/ajra.2013.27.3829.
PubMed 23406585Berkhout MC, Rijntjes E, El Bouazzaoui LH, Fokkens WJ, Brimicombe RW, Heijerman HG. Importance of bacteriology in upper airways of patients with Cystic Fibrosis. J Cyst Fibros. 2013 Sep;12(5):525-9. doi: 10.1016/j.jcf.2013.01.002. Epub 2013 Jan 26.
PubMed 23357546Boucher RC. Human airway ion transport. Part one. Am J Respir Crit Care Med. 1994 Jul;150(1):271-81. doi: 10.1164/ajrccm.150.1.8025763. No abstract available.
PubMed 8025763Boucher RC. Human airway ion transport. Part two. Am J Respir Crit Care Med. 1994 Aug;150(2):581-93. doi: 10.1164/ajrccm.150.2.8049852. No abstract available.
PubMed 8049852Coste A, Gilain L, Roger G, Sebbagh G, Lenoir G, Manach Y, Peynegre R. Endoscopic and CT-scan evaluation of rhinosinusitis in cystic fibrosis. Rhinology. 1995 Sep;33(3):152-6.
PubMed 8560168Digoy GP, Dunn JD, Stoner JA, Christie A, Jones DT. Bacteriology of the paranasal sinuses in pediatric cystic fibrosis patients. Int J Pediatr Otorhinolaryngol. 2012 Jul;76(7):934-8. doi: 10.1016/j.ijporl.2012.02.043. Epub 2012 Apr 17.
PubMed 22513080Durand M, Pourchez J, Aubert G, Le Guellec S, Navarro L, Forest V, Rusch P, Cottier M. Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: new insights into the mechanisms involved. Int J Pharm. 2011 Dec 12;421(1):63-71. doi: 10.1016/j.ijpharm.2011.09.023. Epub 2011 Sep 21.
PubMed 21963472Durand M, Le Guellec S, Pourchez J, Dubois F, Aubert G, Chantrel G, Vecellio L, Hupin C, De Gersem R, Reychler G, Pitance L, Diot P, Jamar F. Sonic aerosol therapy to target maxillary sinuses. Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Oct;129(5):244-50. doi: 10.1016/j.anorl.2011.09.002. Epub 2012 Aug 24.
PubMed 22921302Gysin C, Alothman GA, Papsin BC. Sinonasal disease in cystic fibrosis: clinical characteristics, diagnosis, and management. Pediatr Pulmonol. 2000 Dec;30(6):481-9. doi: 10.1002/1099-0496(200012)30:63.0.co;2-n.
PubMed 11109061Hansen SK, Rau MH, Johansen HK, Ciofu O, Jelsbak L, Yang L, Folkesson A, Jarmer HO, Aanaes K, von Buchwald C, Hoiby N, Molin S. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection. ISME J. 2012 Jan;6(1):31-45. doi: 10.1038/ismej.2011.83. Epub 2011 Jun 30.
PubMed 21716309Kahl BC, Duebbers A, Lubritz G, Haeberle J, Koch HG, Ritzerfeld B, Reilly M, Harms E, Proctor RA, Herrmann M, Peters G. Population dynamics of persistent Staphylococcus aureus isolated from the airways of cystic fibrosis patients during a 6-year prospective study. J Clin Microbiol. 2003 Sep;41(9):4424-7. doi: 10.1128/JCM.41.9.4424-4427.2003.
PubMed 12958283Knowles MR, Robinson JM, Wood RE, Pue CA, Mentz WM, Wager GC, Gatzy JT, Boucher RC. Ion composition of airway surface liquid of patients with cystic fibrosis as compared with normal and disease-control subjects. J Clin Invest. 1997 Nov 15;100(10):2588-95. doi: 10.1172/JCI119802.
PubMed 9366574Konstan MW, Morgan WJ, Butler SM, Pasta DJ, Craib ML, Silva SJ, Stokes DC, Wohl ME, Wagener JS, Regelmann WE, Johnson CA; Scientific Advisory Group and the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis. Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr. 2007 Aug;151(2):134-9, 139.e1. doi: 10.1016/j.jpeds.2007.03.006. Epub 2007 Jun 22.
PubMed 17643762Mainz JG, Naehrlich L, Schien M, Kading M, Schiller I, Mayr S, Schneider G, Wiedemann B, Wiehlmann L, Cramer N, Pfister W, Kahl BC, Beck JF, Tummler B. Concordant genotype of upper and lower airways P aeruginosa and S aureus isolates in cystic fibrosis. Thorax. 2009 Jun;64(6):535-40. doi: 10.1136/thx.2008.104711. Epub 2009 Mar 11.
PubMed 19282318Ramsey BW, Dorkin HL, Eisenberg JD, Gibson RL, Harwood IR, Kravitz RM, Schidlow DV, Wilmott RW, Astley SJ, McBurnie MA, et al. Efficacy of aerosolized tobramycin in patients with cystic fibrosis. N Engl J Med. 1993 Jun 17;328(24):1740-6. doi: 10.1056/NEJM199306173282403.
PubMed 8497284
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Antibiotic (Tobramycin) Delivered by Nebulized Sonic Aerosol for Chronic Rhinosinusitis Treatment of Cystic Fibrosis Patients: A Multicenter Double-blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02888730
- Acronym / sponsor ID
- AVASMUC / AVASMUC
- Conditions
- Cystic Fibrosis, Rhinosinusitis, Lung Diseases
- Keywords
- cystic fibrosis, chronic rhinosinusitis, Lung Diseases, tobramycin, nebulized sonic aerosol therapy
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No suffisant recruitment
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Virginie ESCABASSEUniversity, hospital or other
- Collaborators
- Henri Mondor University Hospital
- Study start
- 16 Feb 2017 (actual)
- Primary completion
- 16 May 2017 (actual)
- Study completion
- 8 Jul 2019 (actual)
- First posted
- 5 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with cystic fibrosis frequently develop chronic rhinosinusitis. Bacterial colonization is facilitated by a reduced mucociliary function and some previous studies suggest that the microbiology of the upper airways might influence the microbiology of the lower airway. The aim of this randomized control study is to demonstrate efficacy of antibiotic delivered by nebulized sonic aerosol therapy to decrease the bacterial load in sinuses and medium ostia and to improve the sino-nasal symptoms and endoscopic scores, quality of life and lung function
Detailed description
Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder in the Caucasian population affecting ~1:3000 children, with a carrier frequency of 1:25. It is a multisystem disorder where pulmonary and sinonasal involvements occur in 90-100% of patients, and up to 86% of children have nasal polyps . Patients with CF develop chronic rhinosinusitis (CRS) due to the defect in the cystic fibrosis Transmembrane Regulator (CFTR) protein. The membrane lining the paranasal sinuses and the nose is identical to the membrane lining the lungs. As in lower airways (LAW) the defect CFTR protein result in viscous mucus . Consequently mucociliary function is reduced, which facilitates bacterial colonization and eventually infection leading to rhinosinusitis . In the past decades infection of the lower airways was the most prominent focus in treatment protocols for CF. Over the years infection of the upper airways (UAW) gradually gained more attention in CF.
Previous research in the microbiology of the upper airways (UAW) in CF displayed that Haemophilus influenzae, Pseudomonas aeruginosa and Staphylococcus aureus were most frequently cultures from the UAW . Since several studies showed concordance between organisms in the UAW and the LAW in CF, the hypothesis evolved that the UAW might influence the patient pulmonary status . Moreover, comparison of UAW and and LAW cultures in CF adult patients showed that Pseudomonas aeruginosa can be cultured from the UAW after eradication therapy which may suggest persistence of Pseudomonas aeruginosa in the UAW . This problem is highlighted in double lung transplant where UAW also appears as a protective niche of adapted clones of bacteria, which can intermittently spread this pathogen to the lung.
CRS treatment in CF patients is based on daily nasal lavages but above all on local or systemic antibiotic treatments to eradicate bacteria in sinuses . Local therapy is favoured in CRS treatment of CF patients to avoid antibiotic side effects, changing organisms or resistance patterns. Sonic aerosol therapy with antibiotics for 15 days is commonly used for CRS in non CF patients to improve sinonasal symptoms and reduce purulent secretions as sound addition in pneumatic aerosol in head corpse's models creates an acoustic pressure at the ostia to improve the aerosol penetration in maxillary sinuses . However its efficacy on bacterial carrying in sinuses is not proved . At the opposite, efficacy of aerosol of tobramycin to LAW was proved in CF patients with a decrease of the density of Pseudomonas aeruginosa, an improvement of FEV, and fewer pulmonary exacerbations .
At the present time, efficacy of antibiotic (tobramycin) delivered by nebulized sonic aerosol for CRS treatment of CF patients is unknown particularly on bacterial carrying.
The aim of this study is to demonstrate that nebulized sonic aerosol therapy with tobramycin in Cystic Fibrosis patients decreases significantly bacterial carrying in sinuses, sinus ostia of middle meatus and sputum compared to nebulized sonic aerosol therapy with placebo and that nebulized sonic aerosol therapy improves sino-nasal symptoms and endoscopic scores, quality of life and lung function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tobramycin nebulized nasally | Experimental | Drug: Tobramycin nebulized nasallyNebulized Tobramycin, one bulb (tobramycin 300 mg and sodium chloride 11.25 mg) nasally twice a day for 15 days |
| Physiologic serum nebulized nasally | Placebo comparator | Drug: Physiologic serum nebulized nasallyNebulized sodium chloride 0.9%, one bulb twice a day nasally for 15 days |
Who may qualify
- Ages
- 7 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Patients older than 7 years followed in the 6 CRCM centers (Créteil, Marseille, Nantes, Toulouse, Clermont-Ferrand and Nice). We choose to enroll children aged 7 years or more because as they have a better adherence to nebulization treatment than younger children.
- Diagnosis of cystic fibrosis confirmed by sweat test (>60mmol/L) and/or the identification of two CF-causing mutations
- Confirmed chronic rhinosinusitis by Ear Nose and Throat doctor by endoscopic examination: bilateral mucopurulent secretions at middle meatus present longer than 12 weeks with or without nasal polyps
- Positive bacteria susceptibility to tobramycin in samples from middle meatus
- Susceptibility of bacteria to tobramycin confirmed
Key exclusion criteria (12 listed)
- - Oral antibiotic therapy one month before enrollment
- enrollment in another protocol with antibiotic
- Ongoing aerosolized tobramycin for endobronchial infection to avoid an overlap between treatment for lung and treatment for sinusitis
- Abnormal auditory acuity (decrease of 20dB in auditory acuity)
- Hypersensibility or allergenecity of aminoglycosides
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tobramycin nebulized nasallyAlso: TobramycinTwo sonic nebulizations per day will be realized by patients: morning and evening during 15 days. There should be a maximum of 12 hours between the 2 doses but shall not be less than 6 hours. The dosage should not be adjusted to body weight. All patients will receive one ampoule of tobramycin twice a dayAmpoules of tobramycin are filled by 5 ml containing 300 mg of tobramycin and 11.25 mg of sodium chloride. Bulb should be employed in nebulizer and administered by the inhalation route approximately 15 minutes to complete.Antibiotic retained for the study, tobramycin is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital. The study's product will be prepared with Base Tobramycin and excipients in accordance with TOBI's composition. | Drug | Tobramycin nebulized nasally |
| Physiologic serum nebulized nasallyAlso: sodium chloride 0.9%Two sonic nebulizations per day will be realized by patients: morning and evening during 15 days. There should be a maximum of 12 hours between the 2 doses but shall not be less than 6 hours. The dosage should not be adjusted to body weight. All patients will receive one ampoule of placebo (Nacl 0.9%) twice a day.Ampoules of placebo are filled by 5 ml containing of sodium chloride. Bulb should be employed in nebulizer and administered by the inhalation route approximately 15 minutes to complete. Placebo for the study is manufactured by the "Pharmacie à Usage Interne" of the Henri Mondor Hospital. Patients in placebo arm will receive 5ml of sodium chloride with the same color (light yellow transparent) as tobramycin | Drug | Physiologic serum nebulized nasally |
Primary outcome
Density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 15
Time frame: 15 days
14 secondary outcomes
density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 30 and 90
Time frame: day 30 and day 90
Minimum inhibitor concentration of sputum bacteria to antibiotics
Time frame: day 15, 30 and 90
Minimum inhibitor concentration of sputum bacteria to tobramycin
Time frame: day 90
Force Vital capacity (FCV) in both groups
Time frame: day 0 and day 30
Forced Expiratory Volume in one second (FEV1) in both groups
Time frame: day 0 and day 30
nasal obstruction at day 90 compared to baseline
Time frame: day 0, 15, 30 and 90
rhinorrhea compared to baseline
Time frame: day 0, 15, 30 and 90
mucopurulent secretions compared to baseline
Time frame: day 0, 15, 30 and 90
facial pain compared to baseline
Time frame: day 0, 15, 30 and 90
dysosmia compared to baseline
Time frame: day 0, 15, 30 and 90
Nasal endoscopic scores compared to baseline in both groups
Time frame: day 0, 15, 30 and 90
Score of the SM5 quality of life questionnaire in both groups
Time frame: day 0, 15, 30 and 90
Score of the SNOT20 quality of life questionnaire in both groups
Time frame: day 0, 15, 30 and 90
Hearing perception of the intensity (in db) and tone (Hz) of sound waves
Time frame: day 0 and day 30
Results and safety
The study was stopped early (reason given: No suffisant recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2023.
- Background: PubMed 23406585Aanaes K, von Buchwald C, Hjuler T, Skov M, Alanin M, Johansen HK. The effect of sinus surgery with intensive follow-up on pathogenic sinus bacteria in patients with cystic fibrosis. Am J Rhinol Allergy. 2013 Jan;27(1):e1-4. doi: 10.2500/ajra.2013.27.3829.
- Background: PubMed 23357546Berkhout MC, Rijntjes E, El Bouazzaoui LH, Fokkens WJ, Brimicombe RW, Heijerman HG. Importance of bacteriology in upper airways of patients with Cystic Fibrosis. J Cyst Fibros. 2013 Sep;12(5):525-9. doi: 10.1016/j.jcf.2013.01.002. Epub 2013 Jan 26.
- Background: PubMed 8025763Boucher RC. Human airway ion transport. Part one. Am J Respir Crit Care Med. 1994 Jul;150(1):271-81. doi: 10.1164/ajrccm.150.1.8025763. No abstract available.
- Background: PubMed 8049852Boucher RC. Human airway ion transport. Part two. Am J Respir Crit Care Med. 1994 Aug;150(2):581-93. doi: 10.1164/ajrccm.150.2.8049852. No abstract available.
- Background: PubMed 8560168Coste A, Gilain L, Roger G, Sebbagh G, Lenoir G, Manach Y, Peynegre R. Endoscopic and CT-scan evaluation of rhinosinusitis in cystic fibrosis. Rhinology. 1995 Sep;33(3):152-6.
- Background: PubMed 22513080Digoy GP, Dunn JD, Stoner JA, Christie A, Jones DT. Bacteriology of the paranasal sinuses in pediatric cystic fibrosis patients. Int J Pediatr Otorhinolaryngol. 2012 Jul;76(7):934-8. doi: 10.1016/j.ijporl.2012.02.043. Epub 2012 Apr 17.
- Background: PubMed 21963472Durand M, Pourchez J, Aubert G, Le Guellec S, Navarro L, Forest V, Rusch P, Cottier M. Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: new insights into the mechanisms involved. Int J Pharm. 2011 Dec 12;421(1):63-71. doi: 10.1016/j.ijpharm.2011.09.023. Epub 2011 Sep 21.
- Background: PubMed 22921302Durand M, Le Guellec S, Pourchez J, Dubois F, Aubert G, Chantrel G, Vecellio L, Hupin C, De Gersem R, Reychler G, Pitance L, Diot P, Jamar F. Sonic aerosol therapy to target maxillary sinuses. Eur Ann Otorhinolaryngol Head Neck Dis. 2012 Oct;129(5):244-50. doi: 10.1016/j.anorl.2011.09.002. Epub 2012 Aug 24.
- Background: PubMed 11109061Gysin C, Alothman GA, Papsin BC. Sinonasal disease in cystic fibrosis: clinical characteristics, diagnosis, and management. Pediatr Pulmonol. 2000 Dec;30(6):481-9. doi: 10.1002/1099-0496(200012)30:63.0.co;2-n.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Virginie Escabasse, MD principal investigator
Creteil Hospital center (CHIC)
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tobramycin nebulized nasally and Physiologic serum nebulized nasally in people with Cystic Fibrosis and Rhinosinusitis, run by Virginie ESCABASSE at 6 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: No suffisant recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Density of bacteria (in CFU/g log10) in sinus ostia of middle meatus samples at day 15 (time frame: 15 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02888730, which also lists 20 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.