Nasal Inhalation of Pulmozyme in Patients With Cystic Fibrosis and Chronic Rhinosinusitis

Study Overview
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Brief Summary
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Rhinosinusitis disorders are often associated with Cystic Fibrosis. They can restrict quality of life enormously and give cause to repeated ENT surgery. The basic defect in CF is a dysfunction of chloride channels in exocrine glands, leading to retention of secretions and consecutive chronic inflammation with bacterial superinfections. The prospective placebo controlled cross-over study aims at the evaluation of a nasally inhalation of Pulmozyme with respect to mucus retention and resulting inflammation.

Official Title
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Nasal Inhalation of Dornase Alfa (Pulmozyme) in Patients With Cystic Fibrosis and Chronic Rhinosinusitis - a Double Blind Placebo-controlled Cross-over, Bicenter, Prospective Clinical Study

Conditions
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Cystic Fibrosis, Rhinosinusitis

Intervention / Treatment
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* Drug: Dornase alfa (Pulmozyme)
* Drug: isotonic saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has a confirmed diagnosis of cystic fibrosis based on: 3 positive sweat chloride tests and/or genetic characterisation Subject is 5 years of age or older Subject has chronic or recurrent rhinosinusitic disorders Subject is able to comply with the procedures scheduled in the protocol Women of childbearing potential are only included into the study, if they are using an effective method of birth control during the protocol (e.g. implants, combined oral contraceptives, injectables, some IUDs, sexual abstinence or vasectomised partner) Exclusion Criteria: Subject has a critical condition defined as: FEV1 < 30% and / or SaO2 < 93% without O2-substitution; need of O2-substitution Subject had an ENT surgery within 6 months prior to study Subject shows signs of nasal bleeding Subject has an ear drum perforation Subject had an acute rhinosinusitis or a pulmonary exacerbation at study entry with need of additional systemic antibiotic therapy Subject has a new therapy with nasal topic steroids during treatment interval Subject has a new systemic steroid therapy Subject is unlikely to comply with the procedures scheduled in the protocol Subject has a known allergic reaction to the medication Subject is pregnant or breastfeeding Patient participates in another clinical trial within 30 days prior to study entry or 30 days after end of the study.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dornase alfa<br>28 days of sinonasal inhalation (Pari Sinus) | Drug: Dornase alfa (Pulmozyme)<br>* 1 x 2,5 ml per day, inhalation use, for 28 days<br>Drug: isotonic saline<br>* 1 x 2,5 ml per day, inhalation use, for 28 days<br>|
| Placebo Comparator: isotonic saline<br>28 days of sinonasal inhalation (Pari Sinus) | Drug: Dornase alfa (Pulmozyme)<br>* 1 x 2,5 ml per day, inhalation use, for 28 days<br>Drug: isotonic saline<br>* 1 x 2,5 ml per day, inhalation use, for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variations in the Sino-nasal-outcome test SNOT-20 adapt CF (primary nasal parameters: obstruction of nasal breathing, sneeze stimulus, permanent nose running, thick-mucous nasal discharge, earaches) |  | day 1, 29, 57 and 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variations in the Sino-nasal-outcome test SNOT-20 adapt CF (secondary nasal parameters, general quality of live parameters and total SNOT 20 adapt. CF score) |  | day 1, 29, 57 and 85 | 
| Changes of pathological alterations visible in MRT images of nose and paranasal sinuses (in selected patients) |  | day 1, 29, 57, 85 | 
| Changes in the nasal lavage fluid and in the serological markers of inflammation |  | day 1, 29, 57 and 85 | 
| Changes in rhinoscopic findings |  | day 1, 29, 57 and 85 | 
| Changes in rhinomanometric findings |  | day 1, 29, 27 and 85 | 
| Incidence of rhinosinusitic and pulmonary exacerbations during therapy |  | day 1 - 85 | 
| Need for decongestants or nasal lavage during treatment |  | day 1 - 85 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis and chronic rhinosinusitis