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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Rhinosinusitis
• Intervention / Treatment: Drug: Dornase alfa (Pulmozyme); Drug: isotonic saline

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Baden-Würtemberg
    • Tübingen, Baden-Würtemberg, Germany, 72076
      • Universitäts-Kinderklinik
  • Thüringen
    • Jena, Thüringen, Germany, 07740
      • Mukoviszidosezentrum der Friedrich-Schiller-Universität

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: University of Jena
• Investigators: Study Chair: Jochen Mainz, M.D., University of Jena

Publications and helpful links

General Publications

• Mainz JG, Michl R, Arnold C. Response to Karadag. J Cyst Fibros. 2014 Sep;13(5):602-3. doi: 10.1016/j.jcf.2014.07.005. Epub 2014 Jul 28. No abstract available.
• Mainz JG, Schien C, Schiller I, Schadlich K, Koitschev A, Koitschev C, Riethmuller J, Graepler-Mainka U, Wiedemann B, Beck JF. Sinonasal inhalation of dornase alfa administered by vibrating aerosol to cystic fibrosis patients: a double-blind placebo-controlled cross-over trial. J Cyst Fibros. 2014 Jul;13(4):461-70. doi: 10.1016/j.jcf.2014.02.005. Epub 2014 Mar 1.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: September 21, 2007
• First Submitted That Met QC Criteria: September 21, 2007
• First Posted (Estimate): September 24, 2007

Study Record Updates

• Last Update Posted (Estimate): December 4, 2014
• Last Update Submitted That Met QC Criteria: December 3, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Cystic Fibrosis and chronic rhinosinusitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Pancreatic Diseases; Fibrosis; Sinusitis; Cystic Fibrosis
• Other Study ID Numbers: pulmozyme-nasal-cf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No